Comparing the effects of argon plasma coagulation and interferon therapy in patients with vaginal intraepithelial neoplasia: a single-center retrospective study

Comparing the effects of argon plasma coagulation and interferon therapy in patients with vaginal intraepithelial neoplasia: a single-center retrospective study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparing the effects of argon plasma coagulation and interferon therapy in patients with vaginal intraepithelial neoplasia: a single-center retrospective study Yuan Gao, Weixin Chu, Lin Hou, Junlan Cheng, Guyue Zhong, Baoguo Xia, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3813329/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Apr, 2024 Read the published version in Archives of Gynecology and Obstetrics → Version 1 posted 4 You are reading this latest preprint version Abstract Purpose This study aimed to evaluate the clinical efficacy and safety of argon plasma coagulation (APC) therapy and interferon therapy in patients with grade I and II vaginal intraepithelial neoplasia (VaIN). Methods A total of 112 patients with VaIN were diagnosed via colposcopy-induced biopsy and classified into the APC group (n = 77) and interferon group (n = 35). Clinical data including age, grade, symptoms, historical or concomitant neoplasia of the lower genital tract, indications for hysterectomy, pregnancy history, cytology, human papillomavirus (HPV) subtype, treatment modalities, and clinical outcomes were analyzed retrospectively. Complications and clinical outcomes were assessed at 6- and 12-month follow-ups. Results There was no significant difference in the HPV clearance rate between the APC (53.42%) and interferon (33.33%) groups at 6-month after treatment. However, the 12-month follow-up of the APC group showed a significantly higher HPV clearance rate as compared to the interferon group (87.67% vs. 51.52%, P < 0.05). The APC group exhibited a significantly higher cure rate (79.22% vs. 40.0%) and lower persistence rate ( 12.99% vs. 37.14%) than the interferon group (P < 0.05). Adverse reaction analysis revealed that the primary reaction in the APC group was vaginal drainage, in contrast to the increased vaginal discharge in the interferon group; though the difference was significant (68.83% vs. 28.57%, P < 0.05), no serious complications were observed. Conclusions Treatment with APC is a safe and more effective procedure against VaIN I and II, compared to interferon. APC may serve as a viable alternative to other physiotherapies. Vaginal intraepithelial neoplasia Argon plasma coagulation Interferon Efficacy Safety Figures Figure 1 1. Introduction Vaginal intraepithelial neoplasia (VaIN) is defined as atypical hyperplasia of different levels limited to the vaginal intraepithelial tissue. VaIN is precancerous lesion that could potentially lead to vaginal carcinoma. In 1952, Graham and Meigs reported on cases of vaginal carcinoma in situ during follow-up after hysterectomy for cervical carcinoma, and first proposed the concept of vaginal intraepithelial neoplasia [ 1 ]. The incidence of VaIN is 0.2-2 per 100,000 women/year[ 2 , 3 ],accounts for only 1.0% of cervical intraepithelial neoplasia (CIN) cases and 0.4%-1.0% of cases of premalignant lesions in the lower genital tract of females [ 4 , 5 ]. However, with the widespread application of Thinprep cytology test (TCT), human papillomavirus (HPV) detection and colposcopy in cervical cancer screening, and increased disease awareness, the prevalence of VaIN has increased steadily in recent years [ 6 ]. The clinical manifestations of VaIN are atypical and few patients present with increased vaginal secretion or contact bleeding. The classical three-step diagnostic model for CIN includes cytological analysis and/or HPV-colposcope-histopathology is recommended for VaIN diagnosis. Histopathological diagnosis guided by colposcopy is considered the gold standard [ 7 ]. Interferon (IFN) has antiviral, immunoregulatory, and antitumor effects, and plays a critical role in the treatment of HPV clearance, chronic hepatitis B/C, and multiple sclerosis [ 14 ]. IFN is widely used for treating HPV-related cervical lesions in China [ 15 ]. Despite the safety profile has been deemed acceptable, information on their efficacy for VaIN patients is limited. The CO 2 laser is used widely in the clinic and has the most treatment experience among physiotherapy, but might lead to local adhesion and vaginal scarring [ 16 ]. Photodynamic therapy is another common treatment method; however, it requires the use of photosensitizers, and often needs to be performed several times [ 6 ]. Therefore, a more safer and user-friendly treatment needs to be found for VaIN patients. Argon plasma coagulation (APC) is a non-contact ablative technique through igniting argon gas into a plasma to cauterize and devitalize vascular tissues to achieve hemostasis or debulking tumors, such as endometriosis or ovarian tumor implants [ 17 , 18 ]. The argon plasma beam can automatically avoid the solidification zone and flow to the insufficient solidification zone, thereby significantly reducing the risk of over solidification [ 19 , 20 ]. In 2012, the FDA determined that the plasma energy system was substantially equivalent to the CO 2 laser system and could thus be used for similar purposes [ 21 ]. APC has been applied for treating gastric low-grade intraepithelial neoplasia, gallbladder cancer, colon polyps, Barrett’s esophagus, and vulval intraepithelial neoplasia [ 22 – 26 ]. However, to date, only one study has evaluated the complications and recurrence rates associated with the use of APC for treating vulvovaginal dysplasia, which just including 16 cases of vaginal HSIL [ 21 ]. In the current study, we performed a retrospective analysis of clinical data obtained from VaIN patients treated with APC or interferon, to compare their treatment outcomes and evaluate the efficacy of argon plasma coagulation treatment. 2. Material and methods 2.1 Study Participants This was a retrospective study that analyzed clinical data from 112 patients treated at the Inpatient Department of Gynecology and Obstetrics at Qingdao Municipal Hospital from January 2018 to November 2022. All patients underwent colposcopy biopsy prior to treatment and were diagnosed with VaIN I or VaIN II. Seventy-seven patients received APC treatment, and thirty-five received interferon therapy. This study was conducted after receiving approval from the Hospital Ethics Committee, and all patients signed an informed consent form before undergoing treatment. The inclusion criteria were as follows: 1. histopathological diagnosis of VaIN guided by colposcopy; 2. patients undergoing a minimum of 12 months of follow-up. The exclusion criteria were as follows: 1. vaginal cancer; 2. acute reproductive tract infection; 3. history of chemoradiotherapy; 4. severe cardiac, liver and renal insufficiency or immune disease; 5. pregnancy or lactation; 6. patients without routine follow-up.Clinical data including the age, grade, symptoms, historical or concomitant neoplasia of the lower genital tract, indications for hysterectomy, pregnancy history, TCT results, HPV subtype, treatment modalities, and clinical outcomes, were collected. 2.2 Procedure 2.2.1 Argon plasma coagulation All treatments were administered in a day surgery setting using an APC therapeutic instrument (Erbe Elektromedizin, Germany, VIO300D) at an output power of 45 W with an argon gas flow of 3.2 L/min. Each patient underwent one-time therapy at 3–7 days after menstruation in a conscious state. Intravenous anesthesia was administered to post-hysterectomy patients to enhance the exposure of retracted vaginal folds and vault corners. Lugol’s iodine was applied at the vagina to outline the non-stained disease area. Ablation was performed from the lesion margin at a distance of 0.3–0.5 cm, with the probe positioned 2–3 mm away from the lesion, until the tissue surface was covered by a yellow and coagulated layer without bleeding. Patients with multifocal disease were treated at the same time. If there was no bleeding or other complication, the patient was discharged on the same day. The procedure was performed by the same accredited specialist colposcopist to ensure a constant APC strategy. 2.2.2 Interferon An interferon α2b capsule (800,000 IU) was inserted into the vaginal fornix in a lithotomy position every night. All patients were treated once a day for 3 months, except during menstruation. Patients were prohibited from having sexual intercourse during treatment and were advised to use condoms after treatment. 2.3 Follow-up and Efficacy evaluation Adverse events, including fever, pain, vaginal bleeding or drainage, pruritus, adhesion, injure of bladder or rectum, or other findings were documented during the check-up and patients were provided targeted treatment if necessary. The first follow-up after treatment was scheduled one month later, along with a pelvic examination. Subsequent follow-ups were scheduled every six months for two years, then annually. At 6 and 12 months, TCT and HPV genotyping were performed and, if indicated, colposcopy and biopsy were performed by an experienced gynecologic oncologist. VaIN diagnosis were confirmed by two independent pathologists. Clinical outcomes were classified into four types: cure, persistence, recurrence, and progression. Cure: no indication for colposcopy according to the screening results, negative colposcopy examination, or negative biopsy at the 6-month follow-up. Persistence: the VaIN grade remained unchanged or decreased by biopsy at the 6-month follow-up. Recurrence: the initial disease was cured at the 6-month follow-up, followed by subsequent recurrence at the 12-month follow-up, as confirmed via biopsy. Progression: biopsy-proven higher grade or invasive cancer at the 6-month follow-up. The HPV clearance rate refers to the proportion of patients with negative conversion of HPV after treatment in patients who were positive for HPV before treatment. 2.4 Statistical analysis Statistical analysis was conducted using SPSS25.0 statistics software (SPSS, Inc, Chicago, USA). Continuous variables were expressed as the mean and standard deviation values. Categorical variables were expressed as percentage values and analyzed using the Chi-square test or Fisher exact test. A P-value less than 0.05 was considered statistically significant. 3. Results 3.1. Clinical Characteristics of Patients A total of 112 women were included, of whom 77 patients received APC therapy, and 35 patients received interferon treatment. Patient characteristics between the two groups showed no statistical significance (Table 1 ). Patients in the study were aged between 21–76 years (mean: 45.71 ± 13.82). Most patients (77.6%) were asymptomatic at diagnosis. Among all the 112 patients, twenty-eight patients (25%) had a prior history of cervical neoplasia. Fifteen patients (13.3%) underwent hysterectomy before receiving a VaIN diagnosis. The most common indication for hysterectomy was cervical cancer (73.3%), followed by high-grade CIN (26.7%). Among the 97 patients who did not undergo hysterectomy, fifty-six (57.7%) had concurrent cervical neoplasia. The general data of patients (including age, gravidity, parity, histopathology, symptoms) were similar between the two groups (P > 0.05) Table 1 Patient characteristics Characteristic APC (n = 77) Interferon(n = 35) P-value Age ༜50 47 16 0.13 ≥ 50 30 19 Gravidity ≤ 1 29 10 0.349 ≥ 2 48 25 Parity ≤ 1 58 27 0.835 ≥ 2 19 8 Previous cervical neoplasia history None 61 23 0.301 CIN 10 7 Cervical cancer 6 5 Previous hysterectomy Yes 9 6 0.550 No 68 29 Hysterectomy indication (n = 15) CIN/CIS 3 1 0.604 Cervical cancer 6 5 Concurrent cervical neoplasia Yes 43 13 0.067 No 34 22 Histopathology VaIN I 48 25 0.349 VaIN II 29 10 Symptoms No 59 28 0.721 Abnormal vaginal bleeding 10 5 Abnormal vaginal discharge 8 2 VaIN, vaginal intraepithelial neoplasia; CIN, cervical intraepithelial neoplasia The results of cytological and HPV genotype analysis were shown in Table 2 . Among the 77 patients in the APC group, there were 22, 20, 25, 7, and 3 cases of NILM, ASCUS, LSIL, HSIL, and ASC-H, respectively; 73 patients were HPV-positive and 36 had multiple HPV infections. In the control group, 33 patients were HPV-positive and 15 had multiple HPV infections; the TCT results showed that 16, 6, 11, 1, and 1 patients were NILM, ASCUS, LSIL, HSIL and ASC-H, respectively. There was no significant difference between the two groups (P > 0.05). Table 2 Cytology test results and HPV infection status for patients Characteristic APC (n = 77) Interferon(n = 35) P-value Cytology test results NILM 22 16 0.369 ASCUS 20 6 LSIL 25 11 HSIL 7 1 ASC-H 3 1 HPV status HPV (+) 73 33 1.000 HPV (-) 4 2 HPV infection Single HPV infection 37 18 0.713 Multiple HPV infections 36 15 HPV genotypes Negative 4 2 0.645 HPV 16 29 10 HPV 18 6 5 Others 41 20 NILM, negative for intraepithelial lesion or malignancy; ASC-US, atypical squamous cells of undetermined significance; LSIL, low-grade squamous intraepithelial lesions; HSIL, high-grade squamous intraepithelial lesions; ASC-H, atypical squamous cells, HSIL cannot be excluded; HPV,human papillomavirus. 3.2 Baseline data in correlation with the VaIN grade At the time of diagnosis, 73 (65.2%) and 39 (34.8%) patients were diagnosed with VaIN I and VaIN II, respectively. The differences in previous history of cervical neoplasia or hysterectomy, and cytology results were not significant among the two grades. ASCUS was the most common finding in VaIN I cases, while squamous intraepithelial lesion (SIL) occurred most commonly in females with VaIN II. However, the proportion of HSIL increases gradually (from 5.48–28.21%) with the increase grade of VaIN (Table 3 ). Table 3 Clinicopathologic characteristics,Cytology test results and HPV infection status in correlation with VaIN grade Characteristic VaIN I(n = 73) VaIN II(n = 39) P-value Previous cervical neoplasia history None 56(76.71%) 27(69.23%) 0.626 CIN 10(13.7%) 8(20.51%) Cervical cancer 7(9.59%) 4(10.26%) Previous hysterectomy Yes 8(10.96%) 7(17.95%) 0.301 No 65(89.04%) 32(82.05%) Concurrent cervical neoplasia No 38(52.05%) 18(46.15%) 0.136 CIN I 22(30.14%) 7(17.95%) CIN II 9(12.33%) 8(20.51%) CIN III 4(5.48%) 6(15.38%) Cytology test results NILM 26(35.62%) 12(30.77%) 0.766 ASCUS 16(21.92%) 10(25.64%) LSIL 25(34.25%) 11(28.21%) HSIL 4(5.48%) 11(28.21%) ASC-H 2(2.74%) 2(5.13%) HPV status HPV (-) 4(5.48%) 2(5.13%) 1.000 HPV (+) 69(94.52%) 37(94.87%) HPV infection Single HPV infection 34(49.28) 21(56.76%) 0.462 Multiple HPV infections 35(50.72) 16(43.24%) HPV genotypes Negative 4(5.33%) 2(5.0%) 0.012 HPV 16 17(22.67%) 21(52.5%) HPV 18 8(10.67%) 2(5.0%) Others 46(61.33%) 15(37.5%) All patients were tested to determine their HPV genotypes. There was a significant statistical difference between the HPV genotype and VaIN grade. In patients with VaIN I, other types of HPV occurred more commonly than HPV 16 (61.33% vs. 22.67%). However, the proportion was reversed in patients with VaIN II (37.5% vs. 52.5%) (p < 0.001; Table 3 ). Among the various genotypes of HPV, the top five most common genotypes were HPV 16 (36.79%), HPV 58 (25.47%), HPV 59 (13.21%), HPV 53 (12.26%), HPV 18 (10.38%), and HPV 56 (10.38%) (Table 4 ). Table 4 HPV genotypes in VaIN HPV infection(n = 106) N* Percentage High-risk HPV HPV 16 39 36.79% HPV 18 11 10.38% HPV 31 9 8.49% HPV 33 9 8.49% HPV 35 3 2.83% HPV 39 4 3.77% HPV 45 0 0% HPV 51 6 5.66% HPV 52 9 8.49% HPV 53 13 12.26% HPV 56 11 10.38% HPV 58 27 25.47% HPV 59 14 13.21% HPV 66 5 4.72% HPV 68 5 4.72% Low-risk HPV HPV 6 4 3.77% HPV 11 2 1.89% HPV 42 2 1.89% HPV 43 3 2.83% HPV 44 1 0.94% HPV 81 6 5.66% *Because of the presence of multiple HPV infections, the total number of cases in the table is more than 106 3.3 Clearance rate of HPV infection At 6 months after treatment, there was no significant difference in the HPV clearance rate between the APC (53.42%,39/73) and interferon (33.33%,11/33) groups. However, the group that underwent a 12-month follow-up after APC exhibited a significantly higher HPV clearance rate than the interferon group (87.67%, (64/73) vs. 51.52%, (17/33), P < 0.05) (Table 5 ). Table 5 Human papillomavirus clearance rate APC (n = 73) Interferon (n = 33) P-value HPV clearance rate at 6-month HPV(-) 53.42% (39/73) 33.33% (11/33) 0.055 HPV(+) 46.58% (34/73) 66.67% (22/33) HPV clearance rate at 12-month HPV(-) 87.67% (64/73) 51.52% (17/33) < 0.001 HPV(+) 12.33% (9/73) 48.48% (16/33) 3.4 Clinical efficacy Based on the 6-month and 12-month follow-up data, among 77 patients in the APC group, 61 (79.22%), 10 (12.99%), 5 (6.49%), and 1 (1.3%) patients experienced cure, persistence, recurrence, and progression, respectively. The corresponding proportion in the interferon group was 40.0% (14/35), 37.14% (13/35), 14.29% (5/35), and 8.57% (3/35), respectively. The APC group exhibited a significantly higher cure rate and lower persistence rate than the interferon group (P < 0.05) (Table 6 ) (Fig. 1 ). Table 6 Evaluation of clinical efficacy Outcome APC (n = 77) Interferon(n = 35) P-value Cure Yes 61 (79.22%) 14 (40.0%) < 0.001 No 16 (20.78%) 21 (60.0%) Persistence Yes 10 (12.99%) 13 (37.14%) 0.003 No 67 (87.01%) 22 (62.86%) Recurrence Yes 5 (6.49%) 5 (14.29%) 0.281 No 72 (93.51%) 28 (85.71%) Progression Yes 1 (1.3%) 3 (8.57%) 0.09 No 76 (98.7%) 32 (91.43%) 3.5 Adverse reactions To determine the safety of APC therapy, we analyzed the rate and type of adverse reactions observed in our patient cohort. The main adverse reaction observed in the APC group was vaginal drainage (53/77), and increased vaginal discharge was observed in the interferon group (10/35), and the differences were significant (P < 0.05). The symptom of vaginal drainage appeared at 7–14 days after treatment and relieved after approximately 30–40 days. Notably, during the 1-month follow-up, 8 patients in the APC group with multifocal lesions developed adhesions. However, these adhesions were loose and could be separated easily using cotton swabs. The vaginal mucosa was smooth and elastic, without obvious scarring and contracture during subsequent long-term follow-ups. Three patients in the APC group experienced vaginal bleeding, which required the use of gauze to apply pressure in the vagina. Of note, those patients undergone concurrent excision and ablation for CIN, and blood appeared from the cervical wound. Overall, most patients experienced no side effects or mild adverse reactions, such as burning or pruritus (Table 7 ). Table 7 Adverse reactions after treatment Symptom APC (n = 77) Interferon(n = 35) P-value Vaginal drainage or increased discharge 53 (68.83%) 10 (28.57%) < 0.001 Burning senseation 3 (3.9%) 5 (14.29%) 0.105 Pruritus of the genital 7 (9.09%) 6 (17.14%) 0.222 Abnormal bleeding 3 (3.9%) 0 (0.0%) 0.551 Vaginal adhesion 8 (10.39%) 0 (0.0%) 0.055 4. Discussion In recent years, the diagnosis and treatment of VaINs have received increased attention. Due to the absence of typical clinical manifestations, the incidence of VaIN has been relatively underestimated. In our study, most patients (77.6%) were asymptomatic at diagnosis, with only a few patients showing abnormal vaginal bleeding or discharge. Age is a high risk factor for VaIN, with a notable association observed between the grade of VaIN and age [ 27 ]. Postmenopausal women showed a 2.09 times higher incidence compared to premenopausal women, due to decreasing estrogen levels, reduced local vaginal resistance, and increasing susceptibility to HPV infection [ 28 ]. A retrospective study of 3229 VaIN patients reported that the mean age of the patients with VaIN I, II, and III was 47.1, 47.1, and 49.9 years, respectively [ 27 ]. The results of our study showed that the mean age was 45.7 years, which is consistent with previous studies. Notably, 10.7% (12/112) of the participants were under the age of 25. VaIN present a trend of youth along with the increasing rate of HPV infection, highlighting the attention for clinicians not to ignore young patients. HPV infection has been proven to be the main etiologic factor for neoplasia in the lower genital tract of females. Mengyin et al. [ 27 ] revealed that the HPV positivity rates of patients with VaIN I, II, and IIII were 89.0%, 92.5%, and 96.8%, respectively, and the rate of multiple infections was lowest in VaIN III. However, Chao et al. suggested that the lowest rate of multiple infections could be observed in patients with VaIN II [ 29 ]. Our results showed the same findings regarding the prevalence rate of HPV, which was 94.52% in VaIN I, and 94.87% in VaIN II. Compared with the multiple HPV infections (50.72%) of VAIN I, single infection (56.76%) was the main pattern of VaIN II.These studies suggested that there may be no correlation between the HPV infection pattern and VaIN grade. The predominant HPV genotype in VaIN patients was HPV 16, followed by 58, 59,53,18, and 56 in our study. Infections with other types (61.33%) were more common in patients with VaIN I, and HPV16 (52.5%) occurred most commonly in those with VaIN II, which was slightly in contrast with the findings of previous studies [ 27 , 30 ]. This might be attribute to variations in different regions, nations, or samples. In addition to the above risk factors, the following reasons might also increase the incidence of VaIN: a history of CIN or cervical cancer (CC), a previous hysterectomy for HPV-related disease, or concomitant cervical neoplasia [ 31 , 32 ]. In the present study, 57.7% of patients had concurrent cervical neoplasia, and 25% had a prior history of cervical neoplasia. Therefore, all patients scheduled for hysterectomy due to CIN or CC should undergo adequate colposcopy examination before surgery to prevent the possibility of overlooking a VaIN diagnosis. During colposcopy, meticulous observation of the vaginal folds, especially the fornix, is of great importance. Long cotton swabs or long flat tweezers can be used if necessary. Until now, the management of VaIN is remained controversial, and there is no unanimous agreement on the best method. As one of the first-line therapies against CIN, interferon can up-regulate the chemotaxis of macrophages and natural killer cells in tissues infected with virus, further modulate the immune system [ 33 ]. APC is an ablative technique that yields results by expelling ionized argon gas onto the target mucosal surface, thereby transferring high-frequency electrical energy to tissues, utilizing thermal effects to deactivate and dry the tissue and cause coagulation and necrosis [ 19 ]. The first use of argon plasma energy in gynecological surgery was reported by Madhuri et al. in 2010, to treat ovarian cancer, ovarian cyst, peritoneal cancer, endometriosis, and myoma [ 34 ]. Until now, only one retrospective cohort study had been conducted to evaluate the effectiveness of APC in patients with vulvovaginal HSIL. After a median follow-up period of 29.3 months for 41 patients treated for vulvar (n = 25) or vaginal (n = 16) HSIL, the recurrence rates (33.3%) and complication rates (4.8%) in the plasma ablation group were similar to the laser ablation group [ 21 ]. However, the effect of APC on VaIN has not been evaluated extensively because of the small sample size and only patients with HSIL were included. In this study, we compared the HPV clearance rates, clinical efficacies, and adverse reactions between patients treated with the interferon and APC therapies. The negative conversion rates of HPV in the APC and interferon groups were 53.42% and 33.33% respectively after 6 months, showing no statistical significance (P > 0.05); however, after 12 months, the values were 87.67% and 51.52%, respectively, and differences were statistically significant, indicating the long-term effect of APC. In the interferon group, lesions disappeared at 6 months in 40% of patients, but recurred at 12 months in 14.29% of the patients. According to Gonçalo et al., approximately 44–81% of all types of VaIN lesions (N = 468) can regress spontaneously, and the rate was 68.8% in LSIL [ 11 ]. Our study showed that the efficacy of interferon therapy was even lower than the expectant management reported by Gonçalo, suggesting that interferon might not be effective for the treatment of VaIN. However, further studies with larger samples and longer follow-up periods are required to confirm this viewpoint. The APC group had a significant higher cure rate (79.22%) and lower persistence rate (12.99%) than the interferon group (P < 0.05), with the recurrence rate being only 6.49%. The results were similar to those observed upon treatment with other ablation methods [ 35 ]. This suggests that APC is more effective than interferon, and can be considered as an alternative physiotherapy strategy for VaIN patients. While there is limited data on the adverse reactions following plasma coagulation in vaginal HSIL, the only two complications were urinary retention in patients with vulval and perianal intraepithelial neoplasia, and pain requiring inpatient management in patients with vulvovaginal and perianal HSIL [ 21 ]. Some physical treatments may lead to serious injuries, such as bladder damage [ 36 ] and sigmoid perforation with sepsis[ 37 ] associated with loop electrosurgical excision, or vaginal vault perforation requiring laparoscopic inspection associated with laser treatment [ 38 ]. However, when the argon beam penetrates through tissue, energy is lost rapidly, causing less damage to surrounding organs or deeper structures. Only mild local adverse reactions were recorded (burning sensation, pruritus, increased vaginal discharge, vaginal bleeding and adhesion), without severe scarring or contracture until the end of follow-up in our study. Eight patients with multifocal lesions developed adhesions that could be easily separated with cotton swabs. As with most patients develop complication of decrustation after physiotherapy, the main reaction in the APC group being vaginal drainage at 7–14 days after treatment, which was resolved at around 30–40 days. 5. Conclusion In conclusion, our results suggest that APC is safe and may result in an improved HPV clearance rate and cure rate, and a reduced recurrence rate, as compared to interferon therapy. Because APC has advantages such as ease of operation, short operation time, fast learning curve for surgeons, no intraoperative bleeding, no need for general anesthesia, and high safety, it may be a reasonable alternative to other physiotherapies for patients with VaIN I and VaIN II. However, a more robust, multicenter, and long-term follow-up RCT is recommended to validate our findings. Declarations Conflict of interest The authors declare that they have no conflict of interests. Ethical approval Approval was obtained from the Ethics Committee of Qingdao Municipal Hospital. Consent for publication All authors have read the manuscript and consent to its publication. Funding ： This work was supported by Natural Science Foundation of Shandong Province (ZR2022QH074) and Shandong Medical and Health Science and Technology Development Plan (202105010641). Authorship contribution statement: YG: Protocol development, responsible surgeon. WXC: Data collection and data analysis. LH: Manuscript editing and review. JLC: Statistical analysis. GYZ: Data collection and data analysis. BGX: Protocol development, patient recruitment. LG: Manuscript editing and review. References GRAHAM J, MEIGS J: Recurrence of tumor after total hysterectomy for carcinoma in situ . American journal of obstetrics and gynecology 1952, 64 (5):1159-1162https://doi.org/10.1016/0002-9378(52)90380-3. Kesic V, Carcopino X, Preti M, Vieira-Baptista P, Bevilacqua F, Bornstein J, Chargari C, Cruickshank M, Erzeneoglu E, Gallio N et al : The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) consensus statement on the management of vaginal intraepithelial neoplasia . International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 2023, 33 (4):446-461https://doi.org/10.1136/ijgc-2022-004213. Sopracordevole F, Barbero M, Clemente N, Fallani M, Cattani P, Agarossi A, De Piero G, Parin A, Frega A, Boselli F et al : High-grade vaginal intraepithelial neoplasia and risk of progression to vaginal cancer: a multicentre study of the Italian Society of Colposcopy and Cervico-Vaginal Pathology (SICPCV) . European review for medical and pharmacological sciences 2016, 20 (5):818-824 Gunderson C, Nugent E, Elfrink S, Gold M, Moore K: A contemporary analysis of epidemiology and management of vaginal intraepithelial neoplasia . American journal of obstetrics and gynecology 2013, 208 (5):410.e411-416https://doi.org/10.1016/j.ajog.2013.01.047. González Bosquet E, Torres A, Busquets M, Esteva C, Muñoz-Almagro C, Lailla J: Prognostic factors for the development of vaginal intraepithelial neoplasia . European journal of gynaecological oncology 2008, 29 (1):43-45 Wang L, Liu X, Zhang J, Li H, Wang X, Fu Y, Liu H, Xu Y, Meng L, Cui B et al : Comparison of ALA-PDT and CO laser treatment of low-grade vaginal intraepithelial neoplasia with high-risk HPV infection: A non-randomized controlled pilot study . Photodiagnosis and photodynamic therapy 2023, 43 :103695https://doi.org/10.1016/j.pdpdt.2023.103695. Hu X, He Y, Lin L, Li X, Luo X, Wang L, Xu C: 5-aminolevulinic acid photodynamic therapy combined with carbon dioxide laser therapy is a safe and effective treatment for vaginal intraepithelial neoplasia . Photodiagnosis and photodynamic therapy 2023, 41 :103259https://doi.org/10.1016/j.pdpdt.2022.103259. WHO classification of tumours of female reproductive organs, 4th ed.; World Health Organization: Geneve, Switzerland, 2014; Available online: [https://publications.iarc.fr/Book-And-Report-Series/Who-Classification-Of-Tumours/WHO-Classification of -Tumors-of-Female-Reproductive-Organs-2014 (accessed on 18 September 2023)] Kim M, Lee I, Lee K: Clinical outcomes and risk of recurrence among patients with vaginal intraepithelial neoplasia: a comprehensive analysis of 576 cases . Journal of gynecologic oncology 2018, 29 (1):e6https://doi.org/10.3802/jgo.2018.29.e6. Hodeib M, Cohen J, Mehta S, Rimel B, Walsh C, Li A, Karlan B, Cass I: Recurrence and risk of progression to lower genital tract malignancy in women with high grade VAIN . Gynecologic oncology 2016, 141 (3):507-510https://doi.org/10.1016/j.ygyno.2016.03.033. Freitas G, Costa A: Non-Excisional therapeutic modalities in vaginal intraepithelial neoplasia . European journal of obstetrics, gynecology, and reproductive biology 2023, 284 :175-179https://doi.org/10.1016/j.ejogrb.2023.03.014. Rountis A, Pergialiotis V, Tsetsa P, Rodolakis A, Haidopoulos D: Management options for vaginal intraepithelial neoplasia . International journal of clinical practice 2020, 74 (11):e13598https://doi.org/10.1111/ijcp.13598. Inayama Y, Takamatsu S, Hamanishi J, Mizuno K, Horinouchi N, Yamanoi K, Taki M, Murakami R, Yamaguchi K, Kosaka K et al : Imiquimod for Cervical and Vaginal Intraepithelial Neoplasia: A Systematic Review and Meta-analysis . Obstetrics and gynecology 2023, 142 (2):307-318https://doi.org/10.1097/aog.0000000000005256. Li R, Hu Y, Wu M, Chen K: Guttate psoriasis induced by interferon alfa-2b suppository treatment for high-grade cervical intraepithelial neoplasia . Dermatologic therapy 2022, 35 (11):e15834https://doi.org/10.1111/dth.15834. Wang W, Liu Y, Pu Y, Li C, Zhou H, Wang Z: Effectiveness of focused ultrasound for high risk human papillomavirus infection-related cervical lesions . International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group 2021, 38 (2):96-102https://doi.org/10.1080/02656736.2021.1910736. He M, Yu E, Hui S, Kung Y: Clinical outcomes of laser vaporization for vaginal intraepithelial neoplasia - A 20-year retrospective review . European journal of obstetrics, gynecology, and reproductive biology 2022, 277 :101-109https://doi.org/10.1016/j.ejogrb.2022.08.017. Prodromidou A, Pandraklakis A, Iavazzo C: The Emerging Role of Neutral Argon Plasma (PlasmaJet) in the Treatment of Advanced Stage Ovarian Cancer: A Systematic Review . Surgical innovation 2020, 27 (3):299-306https://doi.org/10.1177/1553350620908383. Roman H, Auber M, Bourdel N, Martin C, Marpeau L, Puscasiu L: Postoperative recurrence and fertility after endometrioma ablation using plasma energy: retrospective assessment of a 3-year experience . Journal of minimally invasive gynecology 2013, 20 (5):573-582https://doi.org/10.1016/j.jmig.2013.02.016. Grund K, Straub T, Farin G: New haemostatic techniques: argon plasma coagulation . Bailliere's best practice & research Clinical gastroenterology 1999, 13 (1):67-84https://doi.org/10.1053/bega.1999.0009. Che C, Dong F, Wu X, Wang W, Jiang L: Argon gas knife combined with cryotherapy for amyloidosis leading to severe airway stenosis . Respiratory medicine case reports 2019, 28 :100948https://doi.org/10.1016/j.rmcr.2019.100948. Beavis A, Najjar O, Murdock T, Abing A, Fader A, Wethington S, Stone R, Ferriss J, Tanner E, Levinson K: Treatment of vulvar and vaginal dysplasia: plasma energy ablation versus carbon dioxide laser ablation . International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 2021, 31 (11):1410-1415https://doi.org/10.1136/ijgc-2021-002913. Wang N, Chai N, Li L, Li H, Zhai Y, Feng X, Liu S, Zhang W, Linghu E: Comparison of Endoscopic Radiofrequency Ablation and Argon Plasma Coagulation in Patients with Gastric Low-Grade Intraepithelial Neoplasia: A Large-Scale Retrospective Study . Canadian journal of gastroenterology & hepatology 2022, 2022 :2349940https://doi.org/10.1155/2022/2349940. Lee K, Park S, Shin E, Koh D, Lee J: Argon plasma coagulation under direct peroral cholangioscopy for intraductal papillary mucinous neoplasm of the gallbladder . Endoscopy 2023, 55 :E823-E824https://doi.org/10.1055/a-2094-9526. Motz V, Lester C, Moyer M, Maranki J, Levenick J: Hybrid argon plasma coagulation-assisted endoscopic mucosal resection for large sessile colon polyps to reduce local recurrence: a prospective pilot study . Endoscopy 2022, 54 (6):580-584https://doi.org/10.1055/a-1677-3954. Knabe M, Wetzka J, Welsch L, Richl J, Michael F, Blößer S, Heilani M, Kronsbein H, May A: Radiofrequency ablation versus hybrid argon plasma coagulation in Barrett's esophagus: a prospective randomised trial . Surgical endoscopy 2023, 37 (10):7803-7811https://doi.org/10.1007/s00464-023-10313-5. Kushnir C, Fleury A, Hill M, Silver D, Spirtos N: The use of argon beam coagulation in treating vulvar intraepithelial neoplasia III: a retrospective review . Gynecologic oncology 2013, 131 (2):386-388https://doi.org/10.1016/j.ygyno.2013.06.006. Ao M, Zheng D, Wang J, Gu X, Xi M: A retrospective study of cytology and HPV genotypes results of 3229 vaginal intraepithelial neoplasia patients . Journal of medical virology 2022, 94 (2):737-744https://doi.org/10.1002/jmv.27311. Li H, Guo Y, Zhang J, Qiao J, Geng L: Risk factors for the development of vaginal intraepithelial neoplasia . Chinese medical journal 2012, 125 (7):1219-1223 Chao A, Chen T, Hsueh C, Huang C, Yang J, Hsueh S, Huang H, Lin C, Tang Y, Liou J et al : Human papillomavirus in vaginal intraepithelial neoplasia . International journal of cancer 2012, 131 (3):E259-268https://doi.org/10.1002/ijc.27354. Zeng H, Dai Q, Jiang D: A single-institutional retrospective analysis of factors related to vaginal intraepithelial neoplasia . BMC women's health 2023, 23 (1):548https://doi.org/10.1186/s12905-023-02714-4. Stuebs F, Dietl A, Koch M, Adler W, Geppert C, Hartmann A, Knöll A, Mehlhorn G, Beckmann M, Schulmeyer C et al : Cytology and HPV Co-Testing for Detection of Vaginal Intraepithelial Neoplasia: A Retrospective Study . Cancers 2023, 15 (18)https://doi.org/10.3390/cancers15184633. Zhang Y, Xia R, Chen D, Zhang X: Analysis of related factors of cervical intraepithelial neoplasia complicated with vaginal intraepithelial neoplasia . Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 2022, 24 (5):902-908https://doi.org/10.1007/s12094-021-02739-x. Xiong Y, Cui L, Bian C, Zhao X, Wang X: Clearance of human papillomavirus infection in patients with cervical intraepithelial neoplasia: A systemic review and meta-analysis . Medicine 2020, 99 (46):e23155https://doi.org/10.1097/md.0000000000023155. Volcke A, Van Nieuwenhuysen E, Han S, Salihi R, Van Gorp T, Vergote I: Experience with PlasmaJet™ in debulking surgery in 87 patients with advanced-stage ovarian cancer . Journal of surgical oncology 2021, 123 (4):1109-1114https://doi.org/10.1002/jso.26385. Xiong J, Lin Z, He L, Zhang Y, Zeng G, Gui Q: Analysis on the Effect of Radiofrequency Ablation and Electrocautery in the Treatment of Vaginal Intraepithelial Neoplasia . Journal of oncology 2023, 2023 :9432073https://doi.org/10.1155/2023/9432073. Indermaur M, Martino M, Fiorica J, Roberts W, Hoffman M: Upper vaginectomy for the treatment of vaginal intraepithelial neoplasia . American journal of obstetrics and gynecology 2005, 193 (2):577-580; discussion 580-571https://doi.org/10.1016/j.ajog.2005.03.055. Powell J, Asbery D: Treatment of vaginal dysplasia: just a simple loop electrosurgical excision procedure? American journal of obstetrics and gynecology 2000, 182 (3):731-732https://doi.org/10.1067/mob.2000.102701. Bogani G, Ditto A, Martinelli F, Mosca L, Chiappa V, Rossetti D, Leone Roberti Maggiore U, Sabatucci I, Lorusso D, Raspagliesi F: LASER treatment for women with high-grade vaginal intraepithelial neoplasia: A propensity-matched analysis on the efficacy of ablative versus excisional procedures . Lasers in surgery and medicine 2018, 50 (9):933-939https://doi.org/10.1002/lsm.22941. Cite Share Download PDF Status: Published Journal Publication published 29 Apr, 2024 Read the published version in Archives of Gynecology and Obstetrics → Version 1 posted Reviewers agreed at journal 27 Jan, 2024 Reviewers invited by journal 14 Jan, 2024 Editor assigned by journal 29 Dec, 2023 First submitted to journal 28 Dec, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3813329","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":267072743,"identity":"5f50495e-ec30-4356-bf99-ba6ee274016d","order_by":0,"name":"Yuan Gao","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Yuan","middleName":"","lastName":"Gao","suffix":""},{"id":267072744,"identity":"24a980ce-0219-417e-ad0c-c966b077bfa2","order_by":1,"name":"Weixin Chu","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Weixin","middleName":"","lastName":"Chu","suffix":""},{"id":267072745,"identity":"27a221f4-a930-4762-aa8c-77957970bf3c","order_by":2,"name":"Lin Hou","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Lin","middleName":"","lastName":"Hou","suffix":""},{"id":267072746,"identity":"424316ce-c718-4d7c-b5c0-309110a601aa","order_by":3,"name":"Junlan Cheng","email":"","orcid":"https://orcid.org/0009-0009-9455-6117","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Junlan","middleName":"","lastName":"Cheng","suffix":""},{"id":267072747,"identity":"b1c9c2b6-312a-4116-962d-7ade9841271c","order_by":4,"name":"Guyue Zhong","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Guyue","middleName":"","lastName":"Zhong","suffix":""},{"id":267072748,"identity":"dcaade02-be04-4a90-83e6-a679d6dd076f","order_by":5,"name":"Baoguo Xia","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Baoguo","middleName":"","lastName":"Xia","suffix":""},{"id":267072749,"identity":"0f97c4ff-f229-4087-823b-b55aeb116d6e","order_by":6,"name":"Li Guo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyElEQVRIiWNgGAWjYHACxgMJDBYMDOyNjQ8/EKsHqEWCgYHncLOxBNFaGEBaJNLbBHiIUS4fkXzgwIM/Eokbbj5sA+q0k9NtIKDF8EZawoHENqCW24ltDwoYko3NDhDSMiPH4EBiA1hLu4EEw4HEbURpSQA77GCbBA8xWuQlQFrYgFpuMBKpxYDnGdgvxjPPJAID2YAIv8i3Jx98+OOPjWzf8eMPH36osJMjqMUAqsBxAZhhQEA52JYGCG0PY4yCUTAKRsEowAAA7pNMI3cbEsgAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-4653-5428","institution":"Qingdao Municipal Hospital Group","correspondingAuthor":true,"prefix":"","firstName":"Li","middleName":"","lastName":"Guo","suffix":""}],"badges":[],"createdAt":"2023-12-27 18:21:51","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3813329/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3813329/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00404-024-07477-3","type":"published","date":"2024-04-29T23:29:12+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":49712389,"identity":"0c435eb9-8b46-4890-9965-7165a6a8059c","added_by":"auto","created_at":"2024-01-16 20:29:19","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":251001,"visible":true,"origin":"","legend":"\u003cp\u003eColposcopy images before and after treatment of APC and Interferon therapy groups\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3813329/v1/457f52e5aeb5e23126b7bd94.png"},{"id":55698233,"identity":"f2715849-9c02-4e3c-af36-acd52a2749eb","added_by":"auto","created_at":"2024-05-02 02:27:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2154678,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3813329/v1/1a34332f-666a-4a0c-862c-85169238d92a.pdf"}],"financialInterests":"","formattedTitle":"Comparing the effects of argon plasma coagulation and interferon therapy in patients with vaginal intraepithelial neoplasia: a single-center retrospective study","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eVaginal intraepithelial neoplasia (VaIN) is defined as atypical hyperplasia of different levels limited to the vaginal intraepithelial tissue. VaIN is precancerous lesion that could potentially lead to vaginal carcinoma. In 1952, Graham and Meigs reported on cases of vaginal carcinoma in situ during follow-up after hysterectomy for cervical carcinoma, and first proposed the concept of vaginal intraepithelial neoplasia [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The incidence of VaIN is 0.2-2 per 100,000 women/year[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e],accounts for only 1.0% of cervical intraepithelial neoplasia (CIN) cases and 0.4%-1.0% of cases of premalignant lesions in the lower genital tract of females [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, with the widespread application of Thinprep cytology test (TCT), human papillomavirus (HPV) detection and colposcopy in cervical cancer screening, and increased disease awareness, the prevalence of VaIN has increased steadily in recent years [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The clinical manifestations of VaIN are atypical and few patients present with increased vaginal secretion or contact bleeding. The classical three-step diagnostic model for CIN includes cytological analysis and/or HPV-colposcope-histopathology is recommended for VaIN diagnosis. Histopathological diagnosis guided by colposcopy is considered the gold standard [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eInterferon (IFN) has antiviral, immunoregulatory, and antitumor effects, and plays a critical role in the treatment of HPV clearance, chronic hepatitis B/C, and multiple sclerosis [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. IFN is widely used for treating HPV-related cervical lesions in China [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Despite the safety profile has been deemed acceptable, information on their efficacy for VaIN patients is limited. The CO\u003csub\u003e2\u003c/sub\u003e laser is used widely in the clinic and has the most treatment experience among physiotherapy, but might lead to local adhesion and vaginal scarring [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Photodynamic therapy is another common treatment method; however, it requires the use of photosensitizers, and often needs to be performed several times [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Therefore, a more safer and user-friendly treatment needs to be found for VaIN patients. Argon plasma coagulation (APC) is a non-contact ablative technique through igniting argon gas into a plasma to cauterize and devitalize vascular tissues to achieve hemostasis or debulking tumors, such as endometriosis or ovarian tumor implants [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The argon plasma beam can automatically avoid the solidification zone and flow to the insufficient solidification zone, thereby significantly reducing the risk of over solidification [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In 2012, the FDA determined that the plasma energy system was substantially equivalent to the CO\u003csub\u003e2\u003c/sub\u003e laser system and could thus be used for similar purposes [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. APC has been applied for treating gastric low-grade intraepithelial neoplasia, gallbladder cancer, colon polyps, Barrett\u0026rsquo;s esophagus, and vulval intraepithelial neoplasia [\u003cspan additionalcitationids=\"CR23 CR24 CR25\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, to date, only one study has evaluated the complications and recurrence rates associated with the use of APC for treating vulvovaginal dysplasia, which just including 16 cases of vaginal HSIL [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In the current study, we performed a retrospective analysis of clinical data obtained from VaIN patients treated with APC or interferon, to compare their treatment outcomes and evaluate the efficacy of argon plasma coagulation treatment.\u003c/p\u003e"},{"header":"2. Material and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study Participants\u003c/h2\u003e \u003cp\u003eThis was a retrospective study that analyzed clinical data from 112 patients treated at the Inpatient Department of Gynecology and Obstetrics at Qingdao Municipal Hospital from January 2018 to November 2022. All patients underwent colposcopy biopsy prior to treatment and were diagnosed with VaIN I or VaIN II. Seventy-seven patients received APC treatment, and thirty-five received interferon therapy. This study was conducted after receiving approval from the Hospital Ethics Committee, and all patients signed an informed consent form before undergoing treatment. The inclusion criteria were as follows: 1. histopathological diagnosis of VaIN guided by colposcopy; 2. patients undergoing a minimum of 12 months of follow-up. The exclusion criteria were as follows: 1. vaginal cancer; 2. acute reproductive tract infection; 3. history of chemoradiotherapy; 4. severe cardiac, liver and renal insufficiency or immune disease; 5. pregnancy or lactation; 6. patients without routine follow-up.Clinical data including the age, grade, symptoms, historical or concomitant neoplasia of the lower genital tract, indications for hysterectomy, pregnancy history, TCT results, HPV subtype, treatment modalities, and clinical outcomes, were collected.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Procedure\u003c/h2\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003e2.2.1 Argon plasma coagulation\u003c/h2\u003e \u003cp\u003eAll treatments were administered in a day surgery setting using an APC therapeutic instrument (Erbe Elektromedizin, Germany, VIO300D) at an output power of 45 W with an argon gas flow of 3.2 L/min. Each patient underwent one-time therapy at 3\u0026ndash;7 days after menstruation in a conscious state. Intravenous anesthesia was administered to post-hysterectomy patients to enhance the exposure of retracted vaginal folds and vault corners. Lugol\u0026rsquo;s iodine was applied at the vagina to outline the non-stained disease area. Ablation was performed from the lesion margin at a distance of 0.3\u0026ndash;0.5 cm, with the probe positioned 2\u0026ndash;3 mm away from the lesion, until the tissue surface was covered by a yellow and coagulated layer without bleeding. Patients with multifocal disease were treated at the same time. If there was no bleeding or other complication, the patient was discharged on the same day. The procedure was performed by the same accredited specialist colposcopist to ensure a constant APC strategy.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003e2.2.2 Interferon\u003c/h2\u003e \u003cp\u003eAn interferon α2b capsule (800,000 IU) was inserted into the vaginal fornix in a lithotomy position every night. All patients were treated once a day for 3 months, except during menstruation. Patients were prohibited from having sexual intercourse during treatment and were advised to use condoms after treatment.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Follow-up and Efficacy evaluation\u003c/h2\u003e \u003cp\u003eAdverse events, including fever, pain, vaginal bleeding or drainage, pruritus, adhesion, injure of bladder or rectum, or other findings were documented during the check-up and patients were provided targeted treatment if necessary. The first follow-up after treatment was scheduled one month later, along with a pelvic examination. Subsequent follow-ups were scheduled every six months for two years, then annually. At 6 and 12 months, TCT and HPV genotyping were performed and, if indicated, colposcopy and biopsy were performed by an experienced gynecologic oncologist. VaIN diagnosis were confirmed by two independent pathologists.\u003c/p\u003e \u003cp\u003eClinical outcomes were classified into four types: cure, persistence, recurrence, and progression. Cure: no indication for colposcopy according to the screening results, negative colposcopy examination, or negative biopsy at the 6-month follow-up. Persistence: the VaIN grade remained unchanged or decreased by biopsy at the 6-month follow-up. Recurrence: the initial disease was cured at the 6-month follow-up, followed by subsequent recurrence at the 12-month follow-up, as confirmed via biopsy. Progression: biopsy-proven higher grade or invasive cancer at the 6-month follow-up. The HPV clearance rate refers to the proportion of patients with negative conversion of HPV after treatment in patients who were positive for HPV before treatment.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Statistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was conducted using SPSS25.0 statistics software (SPSS, Inc, Chicago, USA). Continuous variables were expressed as the mean and standard deviation values. Categorical variables were expressed as percentage values and analyzed using the Chi-square test or Fisher exact test. A P-value less than 0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n \u003ch2\u003e3.1. Clinical Characteristics of Patients\u003c/h2\u003e\n \u003cp\u003eA total of 112 women were included, of whom 77 patients received APC therapy, and 35 patients received interferon treatment. Patient characteristics between the two groups showed no statistical significance (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Patients in the study were aged between 21\u0026ndash;76 years (mean: 45.71\u0026thinsp;\u0026plusmn;\u0026thinsp;13.82). Most patients (77.6%) were asymptomatic at diagnosis. Among all the 112 patients, twenty-eight patients (25%) had a prior history of cervical neoplasia. Fifteen patients (13.3%) underwent hysterectomy before receiving a VaIN diagnosis. The most common indication for hysterectomy was cervical cancer (73.3%), followed by high-grade CIN (26.7%). Among the 97 patients who did not undergo hysterectomy, fifty-six (57.7%) had concurrent cervical neoplasia. The general data of patients (including age, gravidity, parity, histopathology, symptoms) were similar between the two groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05)\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003ePatient characteristics\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAPC\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;77)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eInterferon(n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e༜50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGravidity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;\u0026thinsp;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.349\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eParity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;\u0026thinsp;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.835\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrevious cervical neoplasia history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.301\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCIN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCervical cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrevious hysterectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.550\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHysterectomy indication (n\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCIN/CIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.604\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCervical cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eConcurrent cervical neoplasia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.067\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHistopathology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVaIN I\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.349\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVaIN II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSymptoms\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.721\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAbnormal vaginal bleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAbnormal vaginal discharge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eVaIN, vaginal intraepithelial neoplasia; CIN, cervical intraepithelial neoplasia\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eThe results of cytological and HPV genotype analysis were shown in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. Among the 77 patients in the APC group, there were 22, 20, 25, 7, and 3 cases of NILM, ASCUS, LSIL, HSIL, and ASC-H, respectively; 73 patients were HPV-positive and 36 had multiple HPV infections. In the control group, 33 patients were HPV-positive and 15 had multiple HPV infections; the TCT results showed that 16, 6, 11, 1, and 1 patients were NILM, ASCUS, LSIL, HSIL and ASC-H, respectively. There was no significant difference between the two groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eCytology test results and HPV infection status for patients\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAPC\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;77)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eInterferon(n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCytology test results\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNILM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.369\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eASCUS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLSIL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHSIL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eASC-H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV (+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV (-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSingle HPV infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.713\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMultiple HPV infections\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV genotypes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.645\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eNILM, negative for intraepithelial lesion or malignancy; ASC-US, atypical squamous cells of undetermined significance; LSIL, low-grade squamous intraepithelial lesions; HSIL, high-grade squamous intraepithelial lesions; ASC-H, atypical squamous cells, HSIL cannot be excluded; HPV,human papillomavirus.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003e3.2 Baseline data in correlation with the VaIN grade\u003c/h2\u003e\n \u003cp\u003eAt the time of diagnosis, 73 (65.2%) and 39 (34.8%) patients were diagnosed with VaIN I and VaIN II, respectively. The differences in previous history of cervical neoplasia or hysterectomy, and cytology results were not significant among the two grades. ASCUS was the most common finding in VaIN I cases, while squamous intraepithelial lesion (SIL) occurred most commonly in females with VaIN II. However, the proportion of HSIL increases gradually (from 5.48\u0026ndash;28.21%) with the increase grade of VaIN (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eClinicopathologic characteristics,Cytology test results and HPV infection status in correlation with VaIN grade\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVaIN I(n\u0026thinsp;=\u0026thinsp;73)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVaIN II(n\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrevious cervical neoplasia history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e56(76.71%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27(69.23%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.626\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCIN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10(13.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8(20.51%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCervical cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7(9.59%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4(10.26%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrevious hysterectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8(10.96%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7(17.95%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.301\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e65(89.04%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e32(82.05%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eConcurrent cervical neoplasia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e38(52.05%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18(46.15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.136\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCIN I\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22(30.14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7(17.95%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCIN II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9(12.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8(20.51%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCIN III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4(5.48%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6(15.38%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCytology test results\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNILM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26(35.62%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12(30.77%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.766\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eASCUS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16(21.92%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10(25.64%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLSIL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25(34.25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11(28.21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHSIL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4(5.48%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11(28.21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eASC-H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2(2.74%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2(5.13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV (-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4(5.48%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2(5.13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV (+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e69(94.52%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e37(94.87%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSingle HPV infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e34(49.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21(56.76%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.462\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMultiple HPV infections\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e35(50.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16(43.24%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV genotypes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4(5.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2(5.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17(22.67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21(52.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8(10.67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2(5.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e46(61.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15(37.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eAll patients were tested to determine their HPV genotypes. There was a significant statistical difference between the HPV genotype and VaIN grade. In patients with VaIN I, other types of HPV occurred more commonly than HPV 16 (61.33% vs. 22.67%). However, the proportion was reversed in patients with VaIN II (37.5% vs. 52.5%) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). Among the various genotypes of HPV, the top five most common genotypes were HPV 16 (36.79%), HPV 58 (25.47%), HPV 59 (13.21%), HPV 53 (12.26%), HPV 18 (10.38%), and HPV 56 (10.38%) (Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eHPV genotypes in VaIN\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"3\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHPV infection(n\u0026thinsp;=\u0026thinsp;106)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN*\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePercentage\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh-risk HPV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.79%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.38%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.49%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.49%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.83%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.77%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.66%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.49%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.26%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.38%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.47%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.21%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.72%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.72%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLow-risk HPV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.77%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.89%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.89%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.83%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.94%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV 81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.66%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\"\u003e*Because of the presence of multiple HPV infections, the total number of cases in the table is more than 106\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003e3.3 Clearance rate of HPV infection\u003c/h2\u003e\n \u003cp\u003eAt 6 months after treatment, there was no significant difference in the HPV clearance rate between the APC (53.42%,39/73) and interferon (33.33%,11/33) groups. However, the group that underwent a 12-month follow-up after APC exhibited a significantly higher HPV clearance rate than the interferon group (87.67%, (64/73) vs. 51.52%, (17/33), P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab5\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eHuman papillomavirus clearance rate\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAPC\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;73)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eInterferon\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;33)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV clearance rate at 6-month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV(-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e53.42% (39/73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33.33% (11/33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV(+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e46.58% (34/73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e66.67% (22/33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV clearance rate at 12-month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV(-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e87.67% (64/73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e51.52% (17/33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHPV(+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12.33% (9/73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e48.48% (16/33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n \u003ch2\u003e3.4 Clinical efficacy\u003c/h2\u003e\n \u003cp\u003eBased on the 6-month and 12-month follow-up data, among 77 patients in the APC group, 61 (79.22%), 10 (12.99%), 5 (6.49%), and 1 (1.3%) patients experienced cure, persistence, recurrence, and progression, respectively. The corresponding proportion in the interferon group was 40.0% (14/35), 37.14% (13/35), 14.29% (5/35), and 8.57% (3/35), respectively. The APC group exhibited a significantly higher cure rate and lower persistence rate than the interferon group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e) (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab6\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eEvaluation of clinical efficacy\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOutcome\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAPC\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;77)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eInterferon(n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e61 (79.22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14 (40.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16 (20.78%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21 (60.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePersistence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10 (12.99%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13 (37.14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e67 (87.01%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22 (62.86%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRecurrence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (6.49%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (14.29%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.281\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e72 (93.51%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28 (85.71%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProgression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (1.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (8.57%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e76 (98.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e32 (91.43%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n \u003ch2\u003e3.5 Adverse reactions\u003c/h2\u003e\n \u003cp\u003eTo determine the safety of APC therapy, we analyzed the rate and type of adverse reactions observed in our patient cohort. The main adverse reaction observed in the APC group was vaginal drainage (53/77), and increased vaginal discharge was observed in the interferon group (10/35), and the differences were significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The symptom of vaginal drainage appeared at 7\u0026ndash;14 days after treatment and relieved after approximately 30\u0026ndash;40 days. Notably, during the 1-month follow-up, 8 patients in the APC group with multifocal lesions developed adhesions. However, these adhesions were loose and could be separated easily using cotton swabs. The vaginal mucosa was smooth and elastic, without obvious scarring and contracture during subsequent long-term follow-ups. Three patients in the APC group experienced vaginal bleeding, which required the use of gauze to apply pressure in the vagina. Of note, those patients undergone concurrent excision and ablation for CIN, and blood appeared from the cervical wound. Overall, most patients experienced no side effects or mild adverse reactions, such as burning or pruritus (Table \u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab7\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eAdverse reactions after treatment\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSymptom\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAPC\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;77)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eInterferon(n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVaginal drainage or increased discharge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e53 (68.83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10 (28.57%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBurning senseation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (3.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (14.29%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.105\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePruritus of the genital\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7 (9.09%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6 (17.14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.222\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAbnormal bleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (3.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.551\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVaginal adhesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (10.39%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eIn recent years, the diagnosis and treatment of VaINs have received increased attention. Due to the absence of typical clinical manifestations, the incidence of VaIN has been relatively underestimated. In our study, most patients (77.6%) were asymptomatic at diagnosis, with only a few patients showing abnormal vaginal bleeding or discharge. Age is a high risk factor for VaIN, with a notable association observed between the grade of VaIN and age [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Postmenopausal women showed a 2.09 times higher incidence compared to premenopausal women, due to decreasing estrogen levels, reduced local vaginal resistance, and increasing susceptibility to HPV infection [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. A retrospective study of 3229 VaIN patients reported that the mean age of the patients with VaIN I, II, and III was 47.1, 47.1, and 49.9 years, respectively [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. The results of our study showed that the mean age was 45.7 years, which is consistent with previous studies. Notably, 10.7% (12/112) of the participants were under the age of 25. VaIN present a trend of youth along with the increasing rate of HPV infection, highlighting the attention for clinicians not to ignore young patients.\u003c/p\u003e \u003cp\u003eHPV infection has been proven to be the main etiologic factor for neoplasia in the lower genital tract of females. Mengyin et al. [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] revealed that the HPV positivity rates of patients with VaIN I, II, and IIII were 89.0%, 92.5%, and 96.8%, respectively, and the rate of multiple infections was lowest in VaIN III. However, Chao et al. suggested that the lowest rate of multiple infections could be observed in patients with VaIN II [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Our results showed the same findings regarding the prevalence rate of HPV, which was 94.52% in VaIN I, and 94.87% in VaIN II. Compared with the multiple HPV infections (50.72%) of VAIN I, single infection (56.76%) was the main pattern of VaIN II.These studies suggested that there may be no correlation between the HPV infection pattern and VaIN grade. The predominant HPV genotype in VaIN patients was HPV 16, followed by 58, 59,53,18, and 56 in our study. Infections with other types (61.33%) were more common in patients with VaIN I, and HPV16 (52.5%) occurred most commonly in those with VaIN II, which was slightly in contrast with the findings of previous studies [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. This might be attribute to variations in different regions, nations, or samples. In addition to the above risk factors, the following reasons might also increase the incidence of VaIN: a history of CIN or cervical cancer (CC), a previous hysterectomy for HPV-related disease, or concomitant cervical neoplasia [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. In the present study, 57.7% of patients had concurrent cervical neoplasia, and 25% had a prior history of cervical neoplasia. Therefore, all patients scheduled for hysterectomy due to CIN or CC should undergo adequate colposcopy examination before surgery to prevent the possibility of overlooking a VaIN diagnosis. During colposcopy, meticulous observation of the vaginal folds, especially the fornix, is of great importance. Long cotton swabs or long flat tweezers can be used if necessary.\u003c/p\u003e \u003cp\u003eUntil now, the management of VaIN is remained controversial, and there is no unanimous agreement on the best method. As one of the first-line therapies against CIN, interferon can up-regulate the chemotaxis of macrophages and natural killer cells in tissues infected with virus, further modulate the immune system [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. APC is an ablative technique that yields results by expelling ionized argon gas onto the target mucosal surface, thereby transferring high-frequency electrical energy to tissues, utilizing thermal effects to deactivate and dry the tissue and cause coagulation and necrosis [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The first use of argon plasma energy in gynecological surgery was reported by Madhuri et al. in 2010, to treat ovarian cancer, ovarian cyst, peritoneal cancer, endometriosis, and myoma [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Until now, only one retrospective cohort study had been conducted to evaluate the effectiveness of APC in patients with vulvovaginal HSIL. After a median follow-up period of 29.3 months for 41 patients treated for vulvar (n\u0026thinsp;=\u0026thinsp;25) or vaginal (n\u0026thinsp;=\u0026thinsp;16) HSIL, the recurrence rates (33.3%) and complication rates (4.8%) in the plasma ablation group were similar to the laser ablation group [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. However, the effect of APC on VaIN has not been evaluated extensively because of the small sample size and only patients with HSIL were included.\u003c/p\u003e \u003cp\u003eIn this study, we compared the HPV clearance rates, clinical efficacies, and adverse reactions between patients treated with the interferon and APC therapies. The negative conversion rates of HPV in the APC and interferon groups were 53.42% and 33.33% respectively after 6 months, showing no statistical significance (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05); however, after 12 months, the values were 87.67% and 51.52%, respectively, and differences were statistically significant, indicating the long-term effect of APC. In the interferon group, lesions disappeared at 6 months in 40% of patients, but recurred at 12 months in 14.29% of the patients. According to Gon\u0026ccedil;alo et al., approximately 44\u0026ndash;81% of all types of VaIN lesions (N\u0026thinsp;=\u0026thinsp;468) can regress spontaneously, and the rate was 68.8% in LSIL [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Our study showed that the efficacy of interferon therapy was even lower than the expectant management reported by Gon\u0026ccedil;alo, suggesting that interferon might not be effective for the treatment of VaIN. However, further studies with larger samples and longer follow-up periods are required to confirm this viewpoint. The APC group had a significant higher cure rate (79.22%) and lower persistence rate (12.99%) than the interferon group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), with the recurrence rate being only 6.49%. The results were similar to those observed upon treatment with other ablation methods [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. This suggests that APC is more effective than interferon, and can be considered as an alternative physiotherapy strategy for VaIN patients.\u003c/p\u003e \u003cp\u003eWhile there is limited data on the adverse reactions following plasma coagulation in vaginal HSIL, the only two complications were urinary retention in patients with vulval and perianal intraepithelial neoplasia, and pain requiring inpatient management in patients with vulvovaginal and perianal HSIL [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Some physical treatments may lead to serious injuries, such as bladder damage [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e] and sigmoid perforation with sepsis[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e] associated with loop electrosurgical excision, or vaginal vault perforation requiring laparoscopic inspection associated with laser treatment [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. However, when the argon beam penetrates through tissue, energy is lost rapidly, causing less damage to surrounding organs or deeper structures. Only mild local adverse reactions were recorded (burning sensation, pruritus, increased vaginal discharge, vaginal bleeding and adhesion), without severe scarring or contracture until the end of follow-up in our study. Eight patients with multifocal lesions developed adhesions that could be easily separated with cotton swabs. As with most patients develop complication of decrustation after physiotherapy, the main reaction in the APC group being vaginal drainage at 7\u0026ndash;14 days after treatment, which was resolved at around 30\u0026ndash;40 days.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eIn conclusion, our results suggest that APC is safe and may result in an improved HPV clearance rate and cure rate, and a reduced recurrence rate, as compared to interferon therapy. Because APC has advantages such as ease of operation, short operation time, fast learning curve for surgeons, no intraoperative bleeding, no need for general anesthesia, and high safety, it may be a reasonable alternative to other physiotherapies for patients with VaIN I and VaIN II. However, a more robust, multicenter, and long-term follow-up RCT is recommended to validate our findings.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of interest\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no conflict of interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u0026nbsp;\u003c/strong\u003eApproval was obtained from the Ethics Committee of Qingdao Municipal Hospital.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003eAll authors have read the manuscript and consent to its publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003cstrong\u003e：\u003c/strong\u003eThis work was supported by Natural Science Foundation of Shandong Province (ZR2022QH074) and Shandong Medical and Health Science and Technology Development Plan (202105010641). \u0026nbsp;\u003c/p\u003e\nAuthorship contribution statement: YG: Protocol development, responsible surgeon. WXC: Data collection and data analysis. LH: Manuscript editing and review. JLC: Statistical analysis. GYZ: Data collection and data analysis. BGX: Protocol development, patient recruitment. LG: Manuscript editing and review.\n\n"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eGRAHAM J, MEIGS J: \u003cstrong\u003eRecurrence of tumor after total hysterectomy for carcinoma in situ\u003c/strong\u003e. \u003cem\u003eAmerican journal of obstetrics and gynecology\u0026nbsp;\u003c/em\u003e1952, \u003cstrong\u003e64\u003c/strong\u003e(5):1159-1162https://doi.org/10.1016/0002-9378(52)90380-3.\u003c/li\u003e\n \u003cli\u003eKesic V, Carcopino X, Preti M, Vieira-Baptista P, Bevilacqua F, Bornstein J, Chargari C, Cruickshank M, Erzeneoglu E, Gallio N\u003cem\u003e\u0026nbsp;et al\u003c/em\u003e: \u003cstrong\u003eThe European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) consensus statement on the management of vaginal intraepithelial neoplasia\u003c/strong\u003e. \u003cem\u003eInternational journal of gynecological cancer : official journal of the International Gynecological Cancer Society\u0026nbsp;\u003c/em\u003e2023, \u003cstrong\u003e33\u003c/strong\u003e(4):446-461https://doi.org/10.1136/ijgc-2022-004213.\u003c/li\u003e\n \u003cli\u003eSopracordevole F, Barbero M, Clemente N, Fallani M, Cattani P, Agarossi A, De Piero G, Parin A, Frega A, Boselli F\u003cem\u003e\u0026nbsp;et al\u003c/em\u003e: \u003cstrong\u003eHigh-grade vaginal intraepithelial neoplasia and risk of progression to vaginal cancer: a multicentre study of the Italian Society of Colposcopy and Cervico-Vaginal Pathology (SICPCV)\u003c/strong\u003e. \u003cem\u003eEuropean review for medical and pharmacological sciences\u0026nbsp;\u003c/em\u003e2016, \u003cstrong\u003e20\u003c/strong\u003e(5):818-824\u003c/li\u003e\n \u003cli\u003eGunderson C, Nugent E, Elfrink S, Gold M, Moore K: \u003cstrong\u003eA contemporary analysis of epidemiology and management of vaginal intraepithelial neoplasia\u003c/strong\u003e. \u003cem\u003eAmerican journal of obstetrics and gynecology\u0026nbsp;\u003c/em\u003e2013, \u003cstrong\u003e208\u003c/strong\u003e(5):410.e411-416https://doi.org/10.1016/j.ajog.2013.01.047.\u003c/li\u003e\n \u003cli\u003eGonz\u0026aacute;lez Bosquet E, Torres A, Busquets M, Esteva C, Mu\u0026ntilde;oz-Almagro C, Lailla J: \u003cstrong\u003ePrognostic factors for the development of vaginal intraepithelial neoplasia\u003c/strong\u003e. \u003cem\u003eEuropean journal of gynaecological oncology\u0026nbsp;\u003c/em\u003e2008, \u003cstrong\u003e29\u003c/strong\u003e(1):43-45\u003c/li\u003e\n \u003cli\u003eWang L, Liu X, Zhang J, Li H, Wang X, Fu Y, Liu H, Xu Y, Meng L, Cui B\u003cem\u003e\u0026nbsp;et al\u003c/em\u003e: \u003cstrong\u003eComparison of ALA-PDT and CO laser treatment of low-grade vaginal intraepithelial neoplasia with high-risk HPV infection: A non-randomized controlled pilot study\u003c/strong\u003e. \u003cem\u003ePhotodiagnosis and photodynamic therapy\u0026nbsp;\u003c/em\u003e2023, \u003cstrong\u003e43\u003c/strong\u003e:103695https://doi.org/10.1016/j.pdpdt.2023.103695.\u003c/li\u003e\n \u003cli\u003eHu X, He Y, Lin L, Li X, Luo X, Wang L, Xu C: \u003cstrong\u003e5-aminolevulinic acid photodynamic therapy combined with carbon dioxide laser therapy is a safe and effective treatment for vaginal intraepithelial neoplasia\u003c/strong\u003e. \u003cem\u003ePhotodiagnosis and photodynamic therapy\u0026nbsp;\u003c/em\u003e2023, \u003cstrong\u003e41\u003c/strong\u003e:103259https://doi.org/10.1016/j.pdpdt.2022.103259.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eWHO classification of tumours of female reproductive organs, 4th ed.; World Health Organization: Geneve, Switzerland, 2014; Available online:\u003c/strong\u003e[https://publications.iarc.fr/Book-And-Report-Series/Who-Classification-Of-Tumours/WHO-Classification of -Tumors-of-Female-Reproductive-Organs-2014 (accessed on 18 September 2023)]\u003c/li\u003e\n \u003cli\u003eKim M, Lee I, Lee K: \u003cstrong\u003eClinical outcomes and risk of recurrence among patients with vaginal intraepithelial neoplasia: a comprehensive analysis of 576 cases\u003c/strong\u003e. \u003cem\u003eJournal of gynecologic oncology\u0026nbsp;\u003c/em\u003e2018, \u003cstrong\u003e29\u003c/strong\u003e(1):e6https://doi.org/10.3802/jgo.2018.29.e6.\u003c/li\u003e\n \u003cli\u003eHodeib M, Cohen J, Mehta S, Rimel B, Walsh C, Li A, Karlan B, Cass I: \u003cstrong\u003eRecurrence and risk of progression to lower genital tract malignancy in women with high grade VAIN\u003c/strong\u003e. \u003cem\u003eGynecologic oncology\u0026nbsp;\u003c/em\u003e2016, \u003cstrong\u003e141\u003c/strong\u003e(3):507-510https://doi.org/10.1016/j.ygyno.2016.03.033.\u003c/li\u003e\n \u003cli\u003eFreitas G, Costa A: \u003cstrong\u003eNon-Excisional therapeutic modalities in vaginal intraepithelial neoplasia\u003c/strong\u003e. \u003cem\u003eEuropean journal of obstetrics, gynecology, and reproductive biology\u0026nbsp;\u003c/em\u003e2023, \u003cstrong\u003e284\u003c/strong\u003e:175-179https://doi.org/10.1016/j.ejogrb.2023.03.014.\u003c/li\u003e\n \u003cli\u003eRountis A, Pergialiotis V, Tsetsa P, Rodolakis A, Haidopoulos D: \u003cstrong\u003eManagement options for vaginal intraepithelial neoplasia\u003c/strong\u003e. \u003cem\u003eInternational journal of clinical practice\u0026nbsp;\u003c/em\u003e2020, \u003cstrong\u003e74\u003c/strong\u003e(11):e13598https://doi.org/10.1111/ijcp.13598.\u003c/li\u003e\n \u003cli\u003eInayama Y, Takamatsu S, Hamanishi J, Mizuno K, Horinouchi N, Yamanoi K, Taki M, Murakami R, Yamaguchi K, Kosaka K\u003cem\u003e\u0026nbsp;et al\u003c/em\u003e: \u003cstrong\u003eImiquimod for Cervical and Vaginal Intraepithelial Neoplasia: A Systematic Review and Meta-analysis\u003c/strong\u003e. \u003cem\u003eObstetrics and gynecology\u0026nbsp;\u003c/em\u003e2023, \u003cstrong\u003e142\u003c/strong\u003e(2):307-318https://doi.org/10.1097/aog.0000000000005256.\u003c/li\u003e\n \u003cli\u003eLi R, Hu Y, Wu M, Chen K: \u003cstrong\u003eGuttate psoriasis induced by interferon alfa-2b suppository treatment for high-grade cervical intraepithelial neoplasia\u003c/strong\u003e. \u003cem\u003eDermatologic therapy\u0026nbsp;\u003c/em\u003e2022, \u003cstrong\u003e35\u003c/strong\u003e(11):e15834https://doi.org/10.1111/dth.15834.\u003c/li\u003e\n \u003cli\u003eWang W, Liu Y, Pu Y, Li C, Zhou H, Wang Z: \u003cstrong\u003eEffectiveness of focused ultrasound for high risk human papillomavirus infection-related cervical lesions\u003c/strong\u003e. \u003cem\u003eInternational journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group\u0026nbsp;\u003c/em\u003e2021, \u003cstrong\u003e38\u003c/strong\u003e(2):96-102https://doi.org/10.1080/02656736.2021.1910736.\u003c/li\u003e\n \u003cli\u003eHe M, Yu E, Hui S, Kung Y: \u003cstrong\u003eClinical outcomes of laser vaporization for vaginal intraepithelial neoplasia - A 20-year retrospective review\u003c/strong\u003e. \u003cem\u003eEuropean journal of obstetrics, gynecology, and reproductive biology\u0026nbsp;\u003c/em\u003e2022, \u003cstrong\u003e277\u003c/strong\u003e:101-109https://doi.org/10.1016/j.ejogrb.2022.08.017.\u003c/li\u003e\n \u003cli\u003eProdromidou A, Pandraklakis A, Iavazzo C: \u003cstrong\u003eThe Emerging Role of Neutral Argon Plasma (PlasmaJet) in the Treatment of Advanced Stage Ovarian Cancer: A Systematic Review\u003c/strong\u003e. \u003cem\u003eSurgical innovation\u0026nbsp;\u003c/em\u003e2020, \u003cstrong\u003e27\u003c/strong\u003e(3):299-306https://doi.org/10.1177/1553350620908383.\u003c/li\u003e\n \u003cli\u003eRoman H, Auber M, Bourdel N, Martin C, Marpeau L, Puscasiu L: \u003cstrong\u003ePostoperative recurrence and fertility after endometrioma ablation using plasma energy: retrospective assessment of a 3-year experience\u003c/strong\u003e. \u003cem\u003eJournal of minimally invasive gynecology\u0026nbsp;\u003c/em\u003e2013, \u003cstrong\u003e20\u003c/strong\u003e(5):573-582https://doi.org/10.1016/j.jmig.2013.02.016.\u003c/li\u003e\n \u003cli\u003eGrund K, Straub T, Farin G: \u003cstrong\u003eNew haemostatic techniques: argon plasma coagulation\u003c/strong\u003e. \u003cem\u003eBailliere\u0026apos;s best practice \u0026amp; research Clinical gastroenterology\u0026nbsp;\u003c/em\u003e1999, \u003cstrong\u003e13\u003c/strong\u003e(1):67-84https://doi.org/10.1053/bega.1999.0009.\u003c/li\u003e\n \u003cli\u003eChe C, Dong F, Wu X, Wang W, Jiang L: \u003cstrong\u003eArgon gas knife combined with cryotherapy for amyloidosis leading to severe airway stenosis\u003c/strong\u003e. \u003cem\u003eRespiratory medicine case reports\u0026nbsp;\u003c/em\u003e2019, \u003cstrong\u003e28\u003c/strong\u003e:100948https://doi.org/10.1016/j.rmcr.2019.100948.\u003c/li\u003e\n \u003cli\u003eBeavis A, Najjar O, Murdock T, Abing A, Fader A, Wethington S, Stone R, Ferriss J, Tanner E, Levinson K: \u003cstrong\u003eTreatment of vulvar and vaginal dysplasia: plasma energy ablation versus carbon dioxide laser ablation\u003c/strong\u003e. \u003cem\u003eInternational journal of gynecological cancer : official journal of the International Gynecological Cancer Society\u0026nbsp;\u003c/em\u003e2021, \u003cstrong\u003e31\u003c/strong\u003e(11):1410-1415https://doi.org/10.1136/ijgc-2021-002913.\u003c/li\u003e\n \u003cli\u003eWang N, Chai N, Li L, Li H, Zhai Y, Feng X, Liu S, Zhang W, Linghu E: \u003cstrong\u003eComparison of Endoscopic Radiofrequency Ablation and Argon Plasma Coagulation in Patients with Gastric Low-Grade Intraepithelial Neoplasia: A Large-Scale Retrospective Study\u003c/strong\u003e. \u003cem\u003eCanadian journal of gastroenterology \u0026amp; hepatology\u0026nbsp;\u003c/em\u003e2022, \u003cstrong\u003e2022\u003c/strong\u003e:2349940https://doi.org/10.1155/2022/2349940.\u003c/li\u003e\n \u003cli\u003eLee K, Park S, Shin E, Koh D, Lee J: \u003cstrong\u003eArgon plasma coagulation under direct peroral cholangioscopy for intraductal papillary mucinous neoplasm of the gallbladder\u003c/strong\u003e. \u003cem\u003eEndoscopy\u0026nbsp;\u003c/em\u003e2023, \u003cstrong\u003e55\u003c/strong\u003e:E823-E824https://doi.org/10.1055/a-2094-9526.\u003c/li\u003e\n \u003cli\u003eMotz V, Lester C, Moyer M, Maranki J, Levenick J: \u003cstrong\u003eHybrid argon plasma coagulation-assisted endoscopic mucosal resection for large sessile colon polyps to reduce local recurrence: a prospective pilot study\u003c/strong\u003e. \u003cem\u003eEndoscopy\u0026nbsp;\u003c/em\u003e2022, \u003cstrong\u003e54\u003c/strong\u003e(6):580-584https://doi.org/10.1055/a-1677-3954.\u003c/li\u003e\n \u003cli\u003eKnabe M, Wetzka J, Welsch L, Richl J, Michael F, Bl\u0026ouml;\u0026szlig;er S, Heilani M, Kronsbein H, May A: \u003cstrong\u003eRadiofrequency ablation versus hybrid argon plasma coagulation in Barrett\u0026apos;s esophagus: a prospective randomised trial\u003c/strong\u003e. \u003cem\u003eSurgical endoscopy\u0026nbsp;\u003c/em\u003e2023, \u003cstrong\u003e37\u003c/strong\u003e(10):7803-7811https://doi.org/10.1007/s00464-023-10313-5.\u003c/li\u003e\n \u003cli\u003eKushnir C, Fleury A, Hill M, Silver D, Spirtos N: \u003cstrong\u003eThe use of argon beam coagulation in treating vulvar intraepithelial neoplasia III: a retrospective review\u003c/strong\u003e. \u003cem\u003eGynecologic oncology\u0026nbsp;\u003c/em\u003e2013, \u003cstrong\u003e131\u003c/strong\u003e(2):386-388https://doi.org/10.1016/j.ygyno.2013.06.006.\u003c/li\u003e\n \u003cli\u003eAo M, Zheng D, Wang J, Gu X, Xi M: \u003cstrong\u003eA retrospective study of cytology and HPV genotypes results of 3229 vaginal intraepithelial neoplasia patients\u003c/strong\u003e. \u003cem\u003eJournal of medical virology\u0026nbsp;\u003c/em\u003e2022, \u003cstrong\u003e94\u003c/strong\u003e(2):737-744https://doi.org/10.1002/jmv.27311.\u003c/li\u003e\n \u003cli\u003eLi H, Guo Y, Zhang J, Qiao J, Geng L: \u003cstrong\u003eRisk factors for the development of vaginal intraepithelial neoplasia\u003c/strong\u003e. \u003cem\u003eChinese medical journal\u0026nbsp;\u003c/em\u003e2012, \u003cstrong\u003e125\u003c/strong\u003e(7):1219-1223\u003c/li\u003e\n \u003cli\u003eChao A, Chen T, Hsueh C, Huang C, Yang J, Hsueh S, Huang H, Lin C, Tang Y, Liou J\u003cem\u003e\u0026nbsp;et al\u003c/em\u003e: \u003cstrong\u003eHuman papillomavirus in vaginal intraepithelial neoplasia\u003c/strong\u003e. \u003cem\u003eInternational journal of cancer\u0026nbsp;\u003c/em\u003e2012, \u003cstrong\u003e131\u003c/strong\u003e(3):E259-268https://doi.org/10.1002/ijc.27354.\u003c/li\u003e\n \u003cli\u003eZeng H, Dai Q, Jiang D: \u003cstrong\u003eA single-institutional retrospective analysis of factors related to vaginal intraepithelial neoplasia\u003c/strong\u003e. \u003cem\u003eBMC women\u0026apos;s health\u0026nbsp;\u003c/em\u003e2023, \u003cstrong\u003e23\u003c/strong\u003e(1):548https://doi.org/10.1186/s12905-023-02714-4.\u003c/li\u003e\n \u003cli\u003eStuebs F, Dietl A, Koch M, Adler W, Geppert C, Hartmann A, Kn\u0026ouml;ll A, Mehlhorn G, Beckmann M, Schulmeyer C\u003cem\u003e\u0026nbsp;et al\u003c/em\u003e: \u003cstrong\u003eCytology and HPV Co-Testing for Detection of Vaginal Intraepithelial Neoplasia: A Retrospective Study\u003c/strong\u003e. \u003cem\u003eCancers\u0026nbsp;\u003c/em\u003e2023, \u003cstrong\u003e15\u003c/strong\u003e(18)https://doi.org/10.3390/cancers15184633.\u003c/li\u003e\n \u003cli\u003eZhang Y, Xia R, Chen D, Zhang X: \u003cstrong\u003eAnalysis of related factors of cervical intraepithelial neoplasia complicated with vaginal intraepithelial neoplasia\u003c/strong\u003e. \u003cem\u003eClinical \u0026amp; translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico\u0026nbsp;\u003c/em\u003e2022, \u003cstrong\u003e24\u003c/strong\u003e(5):902-908https://doi.org/10.1007/s12094-021-02739-x.\u003c/li\u003e\n \u003cli\u003eXiong Y, Cui L, Bian C, Zhao X, Wang X: \u003cstrong\u003eClearance of human papillomavirus infection in patients with cervical intraepithelial neoplasia: A systemic review and meta-analysis\u003c/strong\u003e. \u003cem\u003eMedicine\u0026nbsp;\u003c/em\u003e2020, \u003cstrong\u003e99\u003c/strong\u003e(46):e23155https://doi.org/10.1097/md.0000000000023155.\u003c/li\u003e\n \u003cli\u003eVolcke A, Van Nieuwenhuysen E, Han S, Salihi R, Van Gorp T, Vergote I: \u003cstrong\u003eExperience with PlasmaJet\u0026trade; in debulking surgery in 87 patients with advanced-stage ovarian cancer\u003c/strong\u003e. \u003cem\u003eJournal of surgical oncology\u0026nbsp;\u003c/em\u003e2021, \u003cstrong\u003e123\u003c/strong\u003e(4):1109-1114https://doi.org/10.1002/jso.26385.\u003c/li\u003e\n \u003cli\u003eXiong J, Lin Z, He L, Zhang Y, Zeng G, Gui Q: \u003cstrong\u003eAnalysis on the Effect of Radiofrequency Ablation and Electrocautery in the Treatment of Vaginal Intraepithelial Neoplasia\u003c/strong\u003e. \u003cem\u003eJournal of oncology\u0026nbsp;\u003c/em\u003e2023, \u003cstrong\u003e2023\u003c/strong\u003e:9432073https://doi.org/10.1155/2023/9432073.\u003c/li\u003e\n \u003cli\u003eIndermaur M, Martino M, Fiorica J, Roberts W, Hoffman M: \u003cstrong\u003eUpper vaginectomy for the treatment of vaginal intraepithelial neoplasia\u003c/strong\u003e. \u003cem\u003eAmerican journal of obstetrics and gynecology\u0026nbsp;\u003c/em\u003e2005, \u003cstrong\u003e193\u003c/strong\u003e(2):577-580; discussion 580-571https://doi.org/10.1016/j.ajog.2005.03.055.\u003c/li\u003e\n \u003cli\u003ePowell J, Asbery D: \u003cstrong\u003eTreatment of vaginal dysplasia: just a simple loop electrosurgical excision procedure?\u003c/strong\u003e \u003cem\u003eAmerican journal of obstetrics and gynecology\u0026nbsp;\u003c/em\u003e2000, \u003cstrong\u003e182\u003c/strong\u003e(3):731-732https://doi.org/10.1067/mob.2000.102701.\u003c/li\u003e\n \u003cli\u003eBogani G, Ditto A, Martinelli F, Mosca L, Chiappa V, Rossetti D, Leone Roberti Maggiore U, Sabatucci I, Lorusso D, Raspagliesi F: \u003cstrong\u003eLASER treatment for women with high-grade vaginal intraepithelial neoplasia: A propensity-matched analysis on the efficacy of ablative versus excisional procedures\u003c/strong\u003e. \u003cem\u003eLasers in surgery and medicine\u0026nbsp;\u003c/em\u003e2018, \u003cstrong\u003e50\u003c/strong\u003e(9):933-939https://doi.org/10.1002/lsm.22941.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"archives-of-gynecology-and-obstetrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arch","sideBox":"Learn more about [Archives of Gynecology and Obstetrics](https://www.springer.com/journal/404)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/arch/default.aspx","title":"Archives of Gynecology and Obstetrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Vaginal intraepithelial neoplasia, Argon plasma coagulation, Interferon, Efficacy, Safety","lastPublishedDoi":"10.21203/rs.3.rs-3813329/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3813329/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003ePurpose\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis study aimed to evaluate the clinical efficacy and safety of argon plasma coagulation (APC) therapy and interferon therapy in patients with grade I and II vaginal intraepithelial neoplasia (VaIN).\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eA total of 112 patients with VaIN were diagnosed via colposcopy-induced biopsy and classified into the APC group (n\u0026thinsp;=\u0026thinsp;77) and interferon group (n\u0026thinsp;=\u0026thinsp;35). Clinical data including age, grade, symptoms, historical or concomitant neoplasia of the lower genital tract, indications for hysterectomy, pregnancy history, cytology, human papillomavirus (HPV) subtype, treatment modalities, and clinical outcomes were analyzed retrospectively. Complications and clinical outcomes were assessed at 6- and 12-month follow-ups.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThere was no significant difference in the HPV clearance rate between the APC (53.42%) and interferon (33.33%) groups at 6-month after treatment. However, the 12-month follow-up of the APC group showed a significantly higher HPV clearance rate as compared to the interferon group (87.67% vs. 51.52%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The APC group exhibited a significantly higher cure rate (79.22% vs. 40.0%) and lower persistence rate ( 12.99% vs. 37.14%) than the interferon group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Adverse reaction analysis revealed that the primary reaction in the APC group was vaginal drainage, in contrast to the increased vaginal discharge in the interferon group; though the difference was significant (68.83% vs. 28.57%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), no serious complications were observed.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eTreatment with APC is a safe and more effective procedure against VaIN I and II, compared to interferon. APC may serve as a viable alternative to other physiotherapies.\u003c/p\u003e","manuscriptTitle":"Comparing the effects of argon plasma coagulation and interferon therapy in patients with vaginal intraepithelial neoplasia: a single-center retrospective study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-16 20:29:15","doi":"10.21203/rs.3.rs-3813329/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2024-01-27T13:54:20+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-01-14T17:37:13+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-12-29T12:44:32+00:00","index":"","fulltext":""},{"type":"submitted","content":"Archives of Gynecology and Obstetrics","date":"2023-12-28T20:17:58+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"archives-of-gynecology-and-obstetrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arch","sideBox":"Learn more about [Archives of Gynecology and Obstetrics](https://www.springer.com/journal/404)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/arch/default.aspx","title":"Archives of Gynecology and Obstetrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"4812bff5-242c-42ed-b891-b0b6fe752ad8","owner":[],"postedDate":"January 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-05-01T23:29:12+00:00","versionOfRecord":{"articleIdentity":"rs-3813329","link":"https://doi.org/10.1007/s00404-024-07477-3","journal":{"identity":"archives-of-gynecology-and-obstetrics","isVorOnly":false,"title":"Archives of Gynecology and Obstetrics"},"publishedOn":"2024-04-29 23:29:12","publishedOnDateReadable":"April 29th, 2024"},"versionCreatedAt":"2024-01-16 20:29:15","video":"","vorDoi":"10.1007/s00404-024-07477-3","vorDoiUrl":"https://doi.org/10.1007/s00404-024-07477-3","workflowStages":[]},"version":"v1","identity":"rs-3813329","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3813329","identity":"rs-3813329","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}