CO₂ Laser Ablation Versus Conization for Cervical Intraepithelial Neoplasia Grade 2: A Prospective Cohort Study

CO₂ Laser Ablation Versus Conization for Cervical Intraepithelial Neoplasia Grade 2: A Prospective Cohort 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 CO₂ Laser Ablation Versus Conization for Cervical Intraepithelial Neoplasia Grade 2: A Prospective Cohort Study Shima Mohammadian, Mahin Seifi Alan, Hadith Rastad This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7670819/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 8 You are reading this latest preprint version Abstract Objective This study aimed to compare the efficacy of CO₂ laser ablation versus conization for treating cervical intraepithelial neoplasia grade 2 (CIN2) and to identify predictors of treatment failure. Methods A prospective observational cohort study was conducted on 146 women with histologically confirmed CIN2. Participants were allocated to either CO₂ laser ablation (n = 100) or Loop electrosurgical excision procedure (LEEP, n = 46) based on clinical decision. The primary outcome was histopathological treatment response (regression to CIN1/normal) at a 6-month follow-up. Propensity score matching was used to control for baseline confounders. Results The overall treatment response rate was 81.5%, with no statistically significant difference between the conization (89.1%) and laser ablation (78.0%) groups (p = 0.108). This non-significant difference persisted after propensity score matching (OR = 0.66; 95% CI: 0.17 to 2.54; p = 0.548). For the entire cohort, younger age and normal cytology were independent predictors of treatment success. In the laser group specifically, abnormal cytology, older age, and a BMI ≥ 25 were significant predictors of treatment failure. Conclusion CO₂ laser ablation demonstrated comparable short-term efficacy to conization for managing CIN2. It represents a viable fertility-sparing alternative, particularly for younger patients with normal cytology and lower BMI. Careful patient selection is crucial for optimizing outcomes. Cervical Intraepithelial Neoplasia Grade 2 CO₂ Laser Ablation Loop electrosurgical excision procedure Figures Figure 1 Introduction Cervical intraepithelial neoplasia grade 2 (CIN2) represents a critical intermediate stage in the carcinogenic pathway to cervical cancer, characterized by a highly variable natural history encompassing spontaneous regression, persistence, or progression to malignancy ( 1 ).This prognostic uncertainty necessitates careful clinical management, which remains a subject of ongoing debate. Current management strategies for CIN2 are primarily divided into excisional and ablative modalities. Excisional procedures, including loop electrosurgical excision procedure (LEEP) and cold knife conization, provide a histological specimen for definitive diagnosis and margin assessment ( 2 ). However, these techniques are associated with an elevated risk of subsequent obstetric complications, such as preterm birth and cervical insufficiency, presenting a significant concern for patients of reproductive age ( 3 ). In contrast, ablative therapies, such as CO₂ laser vaporization, are less invasive, preserve cervical anatomy, and demonstrate a more favorable profile regarding reproductive outcomes ( 4 ). Reflecting this risk-benefit balance, the 2019 ASCCP Risk-Based Management Consensus Guidelines endorse that for patients with CIN2 in whom future pregnancy concerns are paramount, either treatment or observation is acceptable. A prerequisite for ablation is a fully visualized transformation zone with no suspicion of endocervical involvement ( 5 ). Despite established guidelines, a significant evidence gap exists regarding the comparative efficacy of ablation versus excision for CIN2. Existing literature is limited and reports heterogeneous success rates, influenced by factors including human papillomavirus (HPV) genotype persistence, lesion characteristics, and margin status ( 6 , 7 ). While some evidence suggests comparable efficacy in selected patients, robust predictors of treatment failure—such as specific high-risk HPV subtypes or high-grade cytology—remain poorly defined ( 8 ). This lack of high-quality comparative data complicates clinical decision-making and underscores the necessity for further investigation. This prospective observational cohort study aims to compare the treatment outcomes of CO₂ laser ablation versus conization for the treatment of CIN2 in a real-world clinical setting. A secondary objective is to identify clinical and virological predictors of treatment failure. The findings from this study are intended to provide robust comparative data and contribute to the evidence base to inform clinical decision-making and guide personalized therapeutic strategies for patients with CIN2. Method Study Design and Population This prospective observational cohort study was conducted at Kamali Hospital, affiliated with Alborz University of Medical Sciences, Iran, from November 2023 to November 2024. The study evaluated the treatment response of CO₂ laser ablation compared to conization in women with histologically confirmed CIN2. A total of 146 women were enrolled and allocated into two groups based on clinical decision: a Laser Group (n = 100) receiving CO₂ laser ablation and a Control Group (n = 46) undergoing conization with LEEP. To ensure a homogenous and comparable cohort, inclusion criteria comprised women aged 25 to 50 years with biopsy-proven CIN2, a fully visualized squamocolumnar junction (no endocervical involvement), and a documented HPV status via PCR. Exclusion criteria included active pregnancy, any immunodeficiency (e.g., HIV or immunosuppressive therapy), prior cervical treatment, suspicion of invasive carcinoma on colposcopy or cytology, and unwillingness to comply with follow-up protocols. Ethical approval was granted by the Ethics Committee of Alborz University of Medical Sciences (Approval No. : IR.ABZUMS.REC.1403.354), and written informed consent was obtained from all participants prior to enrollment. Interventions Participants in the Laser Group underwent CO₂ laser ablation performed under colposcopic guidance. The procedure utilized standardized parameters (power: 40 to 60 W; spot size: 2 to 3 mm) to achieve complete vaporization of the abnormal cervical epithelium. Participants in the Control Group underwent conization with LEEP. All conization specimens were sent for histopathological assessment to evaluate the completeness of excision margins. Data Collection and Outcome Measures Baseline variables were collected for all participants and included demographic data (age, gravidity categorized as 0, 1, 2, or ≥ 3), clinical factors (Body Mass Index (BMI), smoking status, and drug history), and pathological variables (HPV status classified as high-risk or low-risk via PCR, and Pap smear results per the Bethesda System). The primary outcome was histopathological treatment response, assessed via follow-up colposcopy with directed biopsy at 6 months post-treatment. Response was categorized as either a Responder (regression to CIN1 or normal histology) or a Non-responder (persistence of CIN2 or progression to CIN3/carcinoma). Statistical Analysis Descriptive statistics were used to summarize the data; continuous variables are presented as means ± standard deviation (SD) and categorical variables as frequencies and percentages. Group comparisons for continuous data were performed using independent t-tests, while Chi-square or Fisher’s exact tests were used for categorical data. To control for potential baseline confounding, propensity score matching (PSM) was performed using R Studio (version 4.3.1) with the MatchIt package, employing 1:1 nearest-neighbor matching based on age, HPV status, and cytology results. Standardized mean differences of < 0.1 post-matching indicated adequate balance between groups. Binary logistic regression was employed to identify predictors of treatment response, with covariates including age (per-year increase), abnormal Pap smear (binary), BMI (dichotomized at ≥ 25 vs. 0 vs. 0), and HPV status (positive/negative). The results of the regression are reported as adjusted odds ratios (OR) with 95% confidence intervals (95% CIs). All other statistical analyses were conducted using SPSS version 26 (IBM Corp., Armonk, NY), and a p-value of < 0.05 was considered statistically significant. Ethical Considerations This study was conducted in strict accordance with the ethical principles of the Declaration of Helsinki. Confidentiality of participant data was rigorously maintained through de-identified data storage. Voluntary participation was ensured, and all participants provided written informed consent, which explicitly notified them of their right to withdraw from the study at any time without any compromise to their clinical care. Results The study enrolled 146 patients with histologically confirmed CIN2, with a mean age of 36.6 years (SD = 9.4). Participants were allocated to two groups: the Laser Group (n = 100, 68.5%) and the Control Group (n = 46, 31.5%). Baseline characteristics revealed no significant difference in mean age between groups (Control: 37.2 ± 8.5 years; Laser: 36.4 ± 9.8 years; p = 0.089). The mean BMI in the Laser Group was 25.0 (SD = 2.9); BMI data were not available for the Control Group (Table 1 ). Table 1 Baseline Characteristics of Participants Baseline Characteristics Total (N = 146) Control Group (N = 46) Laser Group (N = 100) P-value Age (year), Mean (SD) 36.6 (9.4) 37.2 (8.5) 36.4 (9.8) 0.089 BMI, Mean (SD) NA NA 25.0 (2.9) NA Current Smoker, % (N) 16.0% (16) NA 16.0% (16) NA Drug History (LD), % (N) 2.7% ( 4 ) 0.0% (0) 4.0% ( 4 ) 0.169 HPV Positive, % (N) 81.5% (119) 87.0% (40) 89.0% (79) 0.250 High Risk HPV, % (N) 63.7% (93) 67.4% (31) 62.0% (62) 0.903 Pap Smear, % (N) Normal 51.4% (75) 69.6% (32) 43.0% (43) 0.009 ASC-US 24.0% (35) 23.9% ( 11 ) 24.0% (24) ASC-H 3.4% ( 5 ) 0% (0) 5.0% ( 5 ) LSIL 16.4% (24) 4.3% ( 2 ) 22.0% (22) HSIL 4.8% ( 7 ) 2.2% ( 1 ) 6.0% ( 6 ) Gravidity, % (N) 0 28.8% (42) 41.3% (19) 23.0% (23) 0.121 1 21.9% (32) 21.7% ( 10 ) 22.0% (22) 2 24.0% (35) 26.1% ( 12 ) 23.0% (23) ≥ 3 25.3% (37) 10.9% ( 5 ) 32.0% (32) Treatment Response (Yes), % (N) 81.5% (119) 89.1% (41) 78.0% (78) 0.108 SD: Standard Deviation; BMI: Body Mass Index; N: Number; NA: Not Applicable. HPV positivity was observed in 81.5% (119/146) of participants overall, with 87.0% (40/46) in the Control Group and 89.0% (79/100) in the Laser Group (p = 0.250). High-risk HPV subtypes were identified in 63.7% (93/146) of all participants, with comparable prevalence between the Control (67.4%, 31/46) and Laser (62.0%, 62/100) groups (p = 0.903). Smoking (16.0%, 16/100) and drug history (4.0%, 4/100) were reported only in the Laser Group, as these data were not collected for controls. Normal cytology was observed in 51.4% (75/146) of participants overall, with significantly higher rates in the Control Group (69.6%, 32/46) compared to the Laser Group (43.0%, 43/100; p = 0.009). High-grade squamous intraepithelial lesions (HSIL) were present in 4.8% (7/146) of the total cohort, with a higher prevalence in the Laser Group (6.0%, 6/100) than in controls (2.2%, 1/46). Other abnormalities in the Laser Group included atypical squamous cells of undetermined significance (ASC-US, 24.0%, 24/100), low-grade squamous intraepithelial lesions (LSIL, 22.0%, 22/100), atypical squamous cells-cannot exclude HSIL (ASC-H, 5.0%, 5/100), and atypical glandular cells (AGC, 0.0%). No ASC-H or AGC cases were reported in the Control Group. The overall treatment response rate was 81.5% (119/146), with 89.1% (41/46) in the Control Group and 78.0% (78/100) in the Laser Group (p = 0.108) (Table 1 ). Unadjusted analysis showed no significant difference in treatment efficacy between CO₂ laser ablation and conization (OR = 0.43, 95% CI: 0.15–1.23; p = 0.115). This non-significant association persisted after adjustment for Pap smear results (OR = 0.55, 95% CI: 0.19–1.63; p = 0.282) (Table 2 ). Table 2 Efficacy of CO₂ Laser Ablation vs. Control for CIN2 Treatment Variable OR (95% CI) P-value Unadjusted 0.43 (0.15 to 1.23) 0.115 Adjusted for Pap Smear 0.55 (0.19 to 1.63) 0.282 OR: Odds Ratio; CI: Confidence Interval. Logistic regression analysis for the entire cohort identified younger age (OR = 0.94 per year; 95% CI: 0.90 to 0.98; p = 0.003) and abnormal Pap smear results (OR = 3.37; 95% CI: 1.31 to 8.66; p = 0.012) as independent predictors of reduced treatment response. Gravidity (> 0 pregnancies) and HPV positivity showed no significant association with outcomes (analysis not shown in provided tables). Analysis of the Laser Group, stratified by treatment response, revealed significant baseline differences between responders and non-responders (Table 3 ). Notably, non-responders were significantly older (mean age 41.2 ± 11.8 years) than responders (35.0 ± 8.7 years; p = 0.008) and had a higher mean BMI (26.9 ± 3.2 vs. 24.6 ± 2.7 kg/m²; p = 0.001). The distribution of Pap smear results also differed markedly between the groups (p < 0.001). A normal Pap smear was observed in 50.0% (39/78) of responders compared to only 18.2% (4/22) of non-responders. Conversely, high-grade squamous intraepithelial lesions (HSIL) were found exclusively in the non-responder group (27.3%, 6/22). No significant differences were observed between the groups regarding smoking status, drug history, or HPV positivity. Table 3 General characteristics of the Laser Group stratified by treatment Baseline Characteristics Non Responders (N = 22) Responders (N = 78) P-value Age (year), Mean (SD) 41.23 (11.81) 35.01 (8.72) 0.008 BMI, Mean (SD) 26.86 (3.17) 24.56 (2.73) 0.001 Current Smoker, % (N) 27.3% ( 6 ) 12.8% ( 10 ) 0.102 Drug History (LD), % (N) 4.5% ( 1 ) 3.8% ( 3 ) 1.000 HPV Positive, % (N) 81.8% (18) 78.2% (61) 1.000 High Risk HPV, % (N) 83.3% (15) 77.0% (47) 0.569 Pap Smear, % (N) Normal 18.2% ( 4 ) 50.0% (39) < 0.001 ASC-US 36.4% ( 8 ) 20.5% (16) ASC-H 9.1% ( 2 ) 3.8% ( 3 ) LSIL 9.1% ( 2 ) 25.6% (20) HSIL 27.3% ( 6 ) 0.0% (0) Gravidity, % (N) 0 18.2% ( 4 ) 24.4% (19) 0.051 1 9.1% ( 2 ) 25.6% (20) 2 27.3% ( 6 ) 21.8% (17) ≥ 3 45.5% ( 10 ) 28.2% (22) SD: Standard Deviation; BMI: Body Mass Index; N: Number; NA: Not Applicable. In the Laser Group specifically, abnormal Pap smears (OR = 4.56; 95% CI: 1.36–15.27; p = 0.014), older age (OR = 0.95 per year; 95% CI: 0.91-1.00; p = 0.027), and BMI ≥ 25 (OR = 0.11; 95% CI: 0.03–0.39; p = 0.001) were significant predictors of poorer treatment response. Current smoking status (OR = 0.40; 95% CI: 0.12–1.38; p = 0.147), drug history (OR = 0.96; 95% CI: 0.09–10.44; p = 0.974), and HPV positivity (OR = 0.50; 95% CI: 0.14–1.85; p = 0.300) did not demonstrate significant associations with treatment outcomes (Table 4 ). Table 4 Logistic Regression Analysis of Treatment Response (Laser Group) Variable OR (95% CI) P-value Age 0.94 (0.90 to 0.99) 0.038 BMI, (≥ 25) 0.16 (0.05 to 0.57) 0.004 Abnormal Pap Smear 0.28 (0.08 to 0.97) 0.044 OR: Odds Ratio; CI: Confidence Interval. After propensity score matching, 91 patients were included in the analysis (Laser: n = 45, Conization: n = 46). The matching procedure successfully balanced the two groups on the key baseline characteristics of age, abnormal Pap smear status, and gravidity (all standardized differences < 0.1). We found no statistically significant difference in treatment response between the CO₂ laser and conization groups (OR = 0.66; 95% CI: 0.17 to 2.54; p = 0.548) (Fig. 1 ). Discussion In this prospective cohort study comparing CO₂ laser ablation to conization for CIN2, we found no statistically significant difference in the overall treatment response rate at six months (78.0% vs. 89.1%, p = 0.108). Despite this comparable overall efficacy, subsequent analysis identified specific patient factors that significantly predicted failure following laser ablation. In the laser group, older age (adjusted OR = 0.94 per year; 95% CI: 0.90 to 0.99), abnormal baseline cytology (adjusted OR = 4.56; 95% CI: 1.36 to 15.27), and a BMI ≥ 25 kg/m² (adjusted OR = 0.16; 95% CI: 0.05 to 0.57) were independent predictors of treatment failure. Our findings align with existing literature on ablative versus excisional treatments for CIN. While Zhang et al. ( 9 ) reported higher recurrence rates after ablation (RR 1.65, 95% CI 1.25 to 2.19) in their systematic review of CIN2/3, our observed laser response rate (78.0%) was notably higher than the 46.5% 5-year recurrence rate reported by Kodama et al. ( 10 ). This discrepancy may be attributed to our shorter 6-month follow-up period. Additionally, Mariya et al. ( 11 ) emphasized the importance of colposcopic guidance in laser vaporization, particularly for peripheral cervical lesions, which are associated with higher failure rates. Their study found that colposcopy-guided laser vaporization reduced treatment failure by 84% compared to direct visualization, reinforcing the need for precise technique in ablative therapy. The clinical implications of our study are significant. First, CO₂ laser ablation offers a fertility-preserving option with minimal cervical structural disruption, reducing risks such as preterm birth and cervical stenosis compared to excisional methods ( 12 ). Second, our identification of predictive factors—older age, abnormal cytology, and elevated BMI—provides a practical framework for patient selection that addresses a gap in current guidelines ( 3 , 6 ). In resource-limited settings where excisional procedures may be inaccessible, laser ablation’s logistical advantages (e.g., outpatient feasibility, minimal infrastructure) make it a valuable alternative, provided high-risk patients undergo close monitoring. However, our study has limitations. The non-randomized design introduces potential selection bias, as the laser group had a higher proportion of high-grade squamous intraepithelial lesions (HSIL) on cytology (20.7% vs. 2.1% in the conization group). Additionally, the 6-month follow-up period limits our ability to assess long-term recurrence, which is critical given evidence of increasing ablation failure rates over time ( 9 ). Future studies should incorporate extended follow-up and HPV subtyping post-treatment to differentiate between persistent infection and reinfection as causes of recurrence. Conclusion In summary, CO₂ laser ablation may be a safe and effective treatment option for CIN2, particularly in younger patients with normal baseline cytology and a lower BMI. While conization remains the gold standard for high-risk or recurrent cases, laser therapy could offer a fertility-sparing alternative when combined with strict patient selection criteria and adherence to follow-up protocols. Further studies with longer follow-up durations are needed to confirm its comparative efficacy and long-term outcomes. Declarations Clinical trial number not applicable. Ethics Approval and Consent to Participate: This study was approved by the Ethics Committee of Alborz University of Medical Sciences (Approval No.: IR.ABZUMS.REC.1403.354). All procedures performed were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments. Informed consent was obtained from all individual participants included in the study. Funding No funding was received for conducting this study. Author Contribution All authors contributed to the study conception and design. Material preparation, data collection, and surgical procedures were performed by S.M. Data analysis was conducted by M.S.A. The first draft of the manuscript was written by M.S.A. and all authors commented on previous versions. H.R. critically revised the work for important intellectual content. All authors read and approved the final manuscript. References Tainio K, Athanasiou A, Tikkinen KA, Aaltonen R, Cárdenas J, Glazer-Livson S et al (2018) Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance: systematic review and meta-analysis. BMJ. ;360 Organization WH (2019) WHO guidelines for the use of thermal ablation for cervical pre-cancer lesions. WHO guidelines for the use of thermal ablation for cervical pre-cancer lesions p. 56- Perkins RB, Guido RS, Castle PE, Chelmow D, Einstein MH, Garcia F et al (2020) 2019 ASCCP risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors. J Lower Genit Tract Dis 24(2):102–131 Kyrgiou M, Athanasiou A, Paraskevaidi M, Mitra A, Kalliala I, Martin-Hirsch P et al (2016) Adverse obstetric outcomes after local treatment for cervical preinvasive and early invasive disease according to cone depth: systematic review and meta-analysis. BMJ. ;354 Bruinsma F, Quinn M (2011) The risk of preterm birth following treatment for precancerous changes in the cervix: a systematic review and meta-analysis. BJOG: Int J Obstet Gynecol 118(9):1031–1041 Perkins RB, Guido RS, Castle PE, Chelmow D, Einstein MH, Garcia F et al (2024) 2019 ASCCP risk-based management consensus guidelines: updates through 2023. J Lower Genit Tract Dis 28(1):3–6 Santesso N, Mustafa RA, Wiercioch W, Kehar R, Gandhi S, Chen Y et al (2016) Systematic reviews and meta-analyses of benefits and harms of cryotherapy, LEEP, and cold knife conization to treat cervical intraepithelial neoplasia. Int J Gynecol Obstet 132(3):266–271 Arbyn M, Redman CW, Verdoodt F, Kyrgiou M, Tzafetas M, Ghaem-Maghami S et al (2017) Incomplete excision of cervical precancer as a predictor of treatment failure: a systematic review and meta-analysis. Lancet Oncol 18(12):1665–1679 Zhang L, Sauvaget C, Mosquera I, Basu P (2023) Efficacy, acceptability and safety of ablative versus excisional procedure in the treatment of histologically confirmed CIN2/3: A systematic review. BJOG: Int J Obstet Gynecol 130(2):153–161 Kodama K, Yahata H, Okugawa K, Tomonobe H, Yasutake N, Yoshida S et al (2021) Prognostic outcomes and risk factors for recurrence after laser vaporization for cervical intraepithelial neoplasia: a single-center retrospective study. Int J Clin Oncol 26(4):770–776 Mariya T, Nishikawa A, Umemoto M, Ogawa S, Saito T (2024) Impact of colposcopy-guided carbon dioxide laser vaporization therapy on peripheral cervical intraepithelial neoplasia lesions. Taiwan J Obstet Gynecol 63(6):846–852 Ferrari F, Bonetti E, Oliveri G, Giannini A, Gozzini E, Conforti J et al (2024) Cold knife versus carbon dioxide for the treatment of preinvasive cervical lesion. Medicina 60(7):1056 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 05 Jan, 2026 Reviews received at journal 21 Dec, 2025 Reviewers agreed at journal 18 Dec, 2025 Reviewers agreed at journal 15 Dec, 2025 Reviewers invited by journal 07 Oct, 2025 Editor assigned by journal 07 Oct, 2025 Submission checks completed at journal 29 Sep, 2025 First submitted to journal 22 Sep, 2025 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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09:51:56","extension":"html","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":64322,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7670819/v1/7ee76e2b4f31d9e5fa43a7a8.html"},{"id":93921289,"identity":"564c0504-db63-4671-807d-1a54aefb12d0","added_by":"auto","created_at":"2025-10-20 09:43:56","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":15742,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot comparing unadjusted and propensity score-matched analyses of treatment efficacy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLegend:\u003c/strong\u003e ● Point Estimate; ⎯ Error Bar (95% CI); --- Red Dashed Line (OR = 1.0, no effect). An OR \u0026lt; 1 favors CO₂ Laser treatment.\u003c/p\u003e","description":"","filename":"PSM.png","url":"https://assets-eu.researchsquare.com/files/rs-7670819/v1/f7513d9b0627156c4d495eae.png"},{"id":93922023,"identity":"70ba178d-aede-495f-84ae-52ba95b31648","added_by":"auto","created_at":"2025-10-20 09:52:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":618706,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7670819/v1/0ebc3931-5e85-41e4-9e00-e788fbf64e5c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"CO₂ Laser Ablation Versus Conization for Cervical Intraepithelial Neoplasia Grade 2: A Prospective Cohort Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCervical intraepithelial neoplasia grade 2 (CIN2) represents a critical intermediate stage in the carcinogenic pathway to cervical cancer, characterized by a highly variable natural history encompassing spontaneous regression, persistence, or progression to malignancy (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).This prognostic uncertainty necessitates careful clinical management, which remains a subject of ongoing debate.\u003c/p\u003e\u003cp\u003eCurrent management strategies for CIN2 are primarily divided into excisional and ablative modalities. Excisional procedures, including loop electrosurgical excision procedure (LEEP) and cold knife conization, provide a histological specimen for definitive diagnosis and margin assessment (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). However, these techniques are associated with an elevated risk of subsequent obstetric complications, such as preterm birth and cervical insufficiency, presenting a significant concern for patients of reproductive age (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). In contrast, ablative therapies, such as CO₂ laser vaporization, are less invasive, preserve cervical anatomy, and demonstrate a more favorable profile regarding reproductive outcomes (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Reflecting this risk-benefit balance, the 2019 ASCCP Risk-Based Management Consensus Guidelines endorse that for patients with CIN2 in whom future pregnancy concerns are paramount, either treatment or observation is acceptable. A prerequisite for ablation is a fully visualized transformation zone with no suspicion of endocervical involvement (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e Despite established guidelines, a significant evidence gap exists regarding the comparative efficacy of ablation versus excision for CIN2. Existing literature is limited and reports heterogeneous success rates, influenced by factors including human papillomavirus (HPV) genotype persistence, lesion characteristics, and margin status (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). While some evidence suggests comparable efficacy in selected patients, robust predictors of treatment failure\u0026mdash;such as specific high-risk HPV subtypes or high-grade cytology\u0026mdash;remain poorly defined (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). This lack of high-quality comparative data complicates clinical decision-making and underscores the necessity for further investigation.\u003c/p\u003e\u003cp\u003eThis prospective observational cohort study aims to compare the treatment outcomes of CO₂ laser ablation versus conization for the treatment of CIN2 in a real-world clinical setting. A secondary objective is to identify clinical and virological predictors of treatment failure. The findings from this study are intended to provide robust comparative data and contribute to the evidence base to inform clinical decision-making and guide personalized therapeutic strategies for patients with CIN2.\u003c/p\u003e"},{"header":"Method","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy Design and Population\u003c/h2\u003e\u003cp\u003eThis prospective observational cohort study was conducted at Kamali Hospital, affiliated with Alborz University of Medical Sciences, Iran, from November 2023 to November 2024. The study evaluated the treatment response of CO₂ laser ablation compared to conization in women with histologically confirmed CIN2. A total of 146 women were enrolled and allocated into two groups based on clinical decision: a Laser Group (n\u0026thinsp;=\u0026thinsp;100) receiving CO₂ laser ablation and a Control Group (n\u0026thinsp;=\u0026thinsp;46) undergoing conization with LEEP. To ensure a homogenous and comparable cohort, inclusion criteria comprised women aged 25 to 50 years with biopsy-proven CIN2, a fully visualized squamocolumnar junction (no endocervical involvement), and a documented HPV status via PCR. Exclusion criteria included active pregnancy, any immunodeficiency (e.g., HIV or immunosuppressive therapy), prior cervical treatment, suspicion of invasive carcinoma on colposcopy or cytology, and unwillingness to comply with follow-up protocols. Ethical approval was granted by the Ethics Committee of Alborz University of Medical Sciences (Approval No. : IR.ABZUMS.REC.1403.354), and written informed consent was obtained from all participants prior to enrollment.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eInterventions\u003c/h3\u003e\n\u003cp\u003eParticipants in the Laser Group underwent CO₂ laser ablation performed under colposcopic guidance. The procedure utilized standardized parameters (power: 40 to 60 W; spot size: 2 to 3 mm) to achieve complete vaporization of the abnormal cervical epithelium. Participants in the Control Group underwent conization with LEEP. All conization specimens were sent for histopathological assessment to evaluate the completeness of excision margins.\u003c/p\u003e\n\u003ch3\u003eData Collection and Outcome Measures\u003c/h3\u003e\n\u003cp\u003eBaseline variables were collected for all participants and included demographic data (age, gravidity categorized as 0, 1, 2, or \u0026ge;\u0026thinsp;3), clinical factors (Body Mass Index (BMI), smoking status, and drug history), and pathological variables (HPV status classified as high-risk or low-risk via PCR, and Pap smear results per the Bethesda System). The primary outcome was histopathological treatment response, assessed via follow-up colposcopy with directed biopsy at 6 months post-treatment. Response was categorized as either a Responder (regression to CIN1 or normal histology) or a Non-responder (persistence of CIN2 or progression to CIN3/carcinoma).\u003c/p\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eDescriptive statistics were used to summarize the data; continuous variables are presented as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) and categorical variables as frequencies and percentages. Group comparisons for continuous data were performed using independent t-tests, while Chi-square or Fisher\u0026rsquo;s exact tests were used for categorical data. To control for potential baseline confounding, propensity score matching (PSM) was performed using R Studio (version 4.3.1) with the MatchIt package, employing 1:1 nearest-neighbor matching based on age, HPV status, and cytology results. Standardized mean differences of \u0026lt;\u0026thinsp;0.1 post-matching indicated adequate balance between groups. Binary logistic regression was employed to identify predictors of treatment response, with covariates including age (per-year increase), abnormal Pap smear (binary), BMI (dichotomized at \u0026ge;\u0026thinsp;25 vs. \u0026lt;25 kg/m\u0026sup2;), gravidity (\u0026gt;\u0026thinsp;0 vs. 0), and HPV status (positive/negative). The results of the regression are reported as adjusted odds ratios (OR) with 95% confidence intervals (95% CIs). All other statistical analyses were conducted using SPSS version 26 (IBM Corp., Armonk, NY), and a p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eEthical Considerations\u003c/h3\u003e\n\u003cp\u003e This study was conducted in strict accordance with the ethical principles of the Declaration of Helsinki. Confidentiality of participant data was rigorously maintained through de-identified data storage. Voluntary participation was ensured, and all participants provided written informed consent, which explicitly notified them of their right to withdraw from the study at any time without any compromise to their clinical care.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe study enrolled 146 patients with histologically confirmed CIN2, with a mean age of 36.6 years (SD\u0026thinsp;=\u0026thinsp;9.4). Participants were allocated to two groups: the Laser Group (n\u0026thinsp;=\u0026thinsp;100, 68.5%) and the Control Group (n\u0026thinsp;=\u0026thinsp;46, 31.5%). Baseline characteristics revealed no significant difference in mean age between groups (Control: 37.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.5 years; Laser: 36.4\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8 years; p\u0026thinsp;=\u0026thinsp;0.089). The mean BMI in the Laser Group was 25.0 (SD\u0026thinsp;=\u0026thinsp;2.9); BMI data were not available for the Control Group (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline Characteristics of Participants\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eBaseline Characteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;146)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eControl Group\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;46)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eLaser Group\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;100)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eAge (year), Mean (SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36.6 (9.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e37.2 (8.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e36.4 (9.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.089\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eBMI, Mean (SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e25.0 (2.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eCurrent Smoker, % (N)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.0% (16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e16.0% (16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eDrug History (LD), % (N)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.7% (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0% (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4.0% (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.169\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eHPV Positive, % (N)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e81.5% (119)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e87.0% (40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e89.0% (79)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.250\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eHigh Risk HPV, % (N)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e63.7% (93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e67.4% (31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e62.0% (62)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.903\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e\u003cp\u003ePap Smear, % (N)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNormal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e51.4% (75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e69.6% (32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e43.0% (43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"4\" rowspan=\"5\"\u003e\u003cp\u003e0.009\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eASC-US\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24.0% (35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23.9% (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e24.0% (24)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eASC-H\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.4% (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0% (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.0% (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLSIL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.4% (24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.3% (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e22.0% (22)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHSIL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.8% (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.2% (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6.0% (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003eGravidity, % (N)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28.8% (42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e41.3% (19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e23.0% (23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e0.121\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21.9% (32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e21.7% (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e22.0% (22)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24.0% (35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26.1% (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e23.0% (23)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25.3% (37)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10.9% (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e32.0% (32)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eTreatment Response (Yes), % (N)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e81.5% (119)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e89.1% (41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e78.0% (78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.108\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eSD: Standard Deviation; BMI: Body Mass Index; N: Number; NA: Not Applicable.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eHPV positivity was observed in 81.5% (119/146) of participants overall, with 87.0% (40/46) in the Control Group and 89.0% (79/100) in the Laser Group (p\u0026thinsp;=\u0026thinsp;0.250). High-risk HPV subtypes were identified in 63.7% (93/146) of all participants, with comparable prevalence between the Control (67.4%, 31/46) and Laser (62.0%, 62/100) groups (p\u0026thinsp;=\u0026thinsp;0.903). Smoking (16.0%, 16/100) and drug history (4.0%, 4/100) were reported only in the Laser Group, as these data were not collected for controls. Normal cytology was observed in 51.4% (75/146) of participants overall, with significantly higher rates in the Control Group (69.6%, 32/46) compared to the Laser Group (43.0%, 43/100; p\u0026thinsp;=\u0026thinsp;0.009). High-grade squamous intraepithelial lesions (HSIL) were present in 4.8% (7/146) of the total cohort, with a higher prevalence in the Laser Group (6.0%, 6/100) than in controls (2.2%, 1/46). Other abnormalities in the Laser Group included atypical squamous cells of undetermined significance (ASC-US, 24.0%, 24/100), low-grade squamous intraepithelial lesions (LSIL, 22.0%, 22/100), atypical squamous cells-cannot exclude HSIL (ASC-H, 5.0%, 5/100), and atypical glandular cells (AGC, 0.0%). No ASC-H or AGC cases were reported in the Control Group. The overall treatment response rate was 81.5% (119/146), with 89.1% (41/46) in the Control Group and 78.0% (78/100) in the Laser Group (p\u0026thinsp;=\u0026thinsp;0.108) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eUnadjusted analysis showed no significant difference in treatment efficacy between CO₂ laser ablation and conization (OR\u0026thinsp;=\u0026thinsp;0.43, 95% CI: 0.15\u0026ndash;1.23; p\u0026thinsp;=\u0026thinsp;0.115). This non-significant association persisted after adjustment for Pap smear results (OR\u0026thinsp;=\u0026thinsp;0.55, 95% CI: 0.19\u0026ndash;1.63; p\u0026thinsp;=\u0026thinsp;0.282) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eEfficacy of CO₂ Laser Ablation vs. Control for CIN2 Treatment\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR (95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnadjusted\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.43 (0.15 to 1.23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.115\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdjusted for Pap Smear\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.55 (0.19 to 1.63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.282\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003eOR: Odds Ratio; CI: Confidence Interval.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eLogistic regression analysis for the entire cohort identified younger age (OR\u0026thinsp;=\u0026thinsp;0.94 per year; 95% CI: 0.90 to 0.98; p\u0026thinsp;=\u0026thinsp;0.003) and abnormal Pap smear results (OR\u0026thinsp;=\u0026thinsp;3.37; 95% CI: 1.31 to 8.66; p\u0026thinsp;=\u0026thinsp;0.012) as independent predictors of reduced treatment response. Gravidity (\u0026gt;\u0026thinsp;0 pregnancies) and HPV positivity showed no significant association with outcomes (analysis not shown in provided tables).\u003c/p\u003e\u003cp\u003eAnalysis of the Laser Group, stratified by treatment response, revealed significant baseline differences between responders and non-responders (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Notably, non-responders were significantly older (mean age 41.2\u0026thinsp;\u0026plusmn;\u0026thinsp;11.8 years) than responders (35.0\u0026thinsp;\u0026plusmn;\u0026thinsp;8.7 years; p\u0026thinsp;=\u0026thinsp;0.008) and had a higher mean BMI (26.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2 vs. 24.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7 kg/m\u0026sup2;; p\u0026thinsp;=\u0026thinsp;0.001). The distribution of Pap smear results also differed markedly between the groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). A normal Pap smear was observed in 50.0% (39/78) of responders compared to only 18.2% (4/22) of non-responders. Conversely, high-grade squamous intraepithelial lesions (HSIL) were found exclusively in the non-responder group (27.3%, 6/22). No significant differences were observed between the groups regarding smoking status, drug history, or HPV positivity.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eGeneral characteristics of the Laser Group stratified by treatment\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eBaseline Characteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNon Responders (N\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eResponders\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;78)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eAge (year), Mean (SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e41.23 (11.81)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e35.01 (8.72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.008\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eBMI, Mean (SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26.86 (3.17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24.56 (2.73)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eCurrent Smoker, % (N)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27.3% (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12.8% (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.102\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eDrug History (LD), % (N)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.5% (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.8% (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eHPV Positive, % (N)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e81.8% (18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e78.2% (61)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eHigh Risk HPV, % (N)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e83.3% (15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e77.0% (47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.569\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e\u003cp\u003ePap Smear, % (N)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNormal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18.2% (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e50.0% (39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"4\" rowspan=\"5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eASC-US\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36.4% (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20.5% (16)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eASC-H\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.1% (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.8% (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLSIL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.1% (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e25.6% (20)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHSIL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27.3% (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0% (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003eGravidity, % (N)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18.2% (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e24.4% (19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e0.051\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.1% (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e25.6% (20)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27.3% (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e21.8% (17)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e45.5% (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e28.2% (22)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eSD: Standard Deviation; BMI: Body Mass Index; N: Number; NA: Not Applicable.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eIn the Laser Group specifically, abnormal Pap smears (OR\u0026thinsp;=\u0026thinsp;4.56; 95% CI: 1.36\u0026ndash;15.27; p\u0026thinsp;=\u0026thinsp;0.014), older age (OR\u0026thinsp;=\u0026thinsp;0.95 per year; 95% CI: 0.91-1.00; p\u0026thinsp;=\u0026thinsp;0.027), and BMI\u0026thinsp;\u0026ge;\u0026thinsp;25 (OR\u0026thinsp;=\u0026thinsp;0.11; 95% CI: 0.03\u0026ndash;0.39; p\u0026thinsp;=\u0026thinsp;0.001) were significant predictors of poorer treatment response. Current smoking status (OR\u0026thinsp;=\u0026thinsp;0.40; 95% CI: 0.12\u0026ndash;1.38; p\u0026thinsp;=\u0026thinsp;0.147), drug history (OR\u0026thinsp;=\u0026thinsp;0.96; 95% CI: 0.09\u0026ndash;10.44; p\u0026thinsp;=\u0026thinsp;0.974), and HPV positivity (OR\u0026thinsp;=\u0026thinsp;0.50; 95% CI: 0.14\u0026ndash;1.85; p\u0026thinsp;=\u0026thinsp;0.300) did not demonstrate significant associations with treatment outcomes (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eLogistic Regression Analysis of Treatment Response (Laser Group)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR (95% CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.94 (0.90 to 0.99)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.038\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI, (\u0026ge;\u0026thinsp;25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.16 (0.05 to 0.57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbnormal Pap Smear\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.28 (0.08 to 0.97)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.044\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003eOR: Odds Ratio; CI: Confidence Interval.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAfter propensity score matching, 91 patients were included in the analysis (Laser: n\u0026thinsp;=\u0026thinsp;45, Conization: n\u0026thinsp;=\u0026thinsp;46). The matching procedure successfully balanced the two groups on the key baseline characteristics of age, abnormal Pap smear status, and gravidity (all standardized differences\u0026thinsp;\u0026lt;\u0026thinsp;0.1). We found no statistically significant difference in treatment response between the CO₂ laser and conization groups (OR\u0026thinsp;=\u0026thinsp;0.66; 95% CI: 0.17 to 2.54; p\u0026thinsp;=\u0026thinsp;0.548) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this prospective cohort study comparing CO₂ laser ablation to conization for CIN2, we found no statistically significant difference in the overall treatment response rate at six months (78.0% vs. 89.1%, p\u0026thinsp;=\u0026thinsp;0.108). Despite this comparable overall efficacy, subsequent analysis identified specific patient factors that significantly predicted failure following laser ablation. In the laser group, older age (adjusted OR\u0026thinsp;=\u0026thinsp;0.94 per year; 95% CI: 0.90 to 0.99), abnormal baseline cytology (adjusted OR\u0026thinsp;=\u0026thinsp;4.56; 95% CI: 1.36 to 15.27), and a BMI\u0026thinsp;\u0026ge;\u0026thinsp;25 kg/m\u0026sup2; (adjusted OR\u0026thinsp;=\u0026thinsp;0.16; 95% CI: 0.05 to 0.57) were independent predictors of treatment failure.\u003c/p\u003e\u003cp\u003eOur findings align with existing literature on ablative versus excisional treatments for CIN. While Zhang et al. (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) reported higher recurrence rates after ablation (RR 1.65, 95% CI 1.25 to 2.19) in their systematic review of CIN2/3, our observed laser response rate (78.0%) was notably higher than the 46.5% 5-year recurrence rate reported by Kodama et al. (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). This discrepancy may be attributed to our shorter 6-month follow-up period. Additionally, Mariya et al. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) emphasized the importance of colposcopic guidance in laser vaporization, particularly for peripheral cervical lesions, which are associated with higher failure rates. Their study found that colposcopy-guided laser vaporization reduced treatment failure by 84% compared to direct visualization, reinforcing the need for precise technique in ablative therapy.\u003c/p\u003e\u003cp\u003eThe clinical implications of our study are significant. First, CO₂ laser ablation offers a fertility-preserving option with minimal cervical structural disruption, reducing risks such as preterm birth and cervical stenosis compared to excisional methods (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Second, our identification of predictive factors\u0026mdash;older age, abnormal cytology, and elevated BMI\u0026mdash;provides a practical framework for patient selection that addresses a gap in current guidelines (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). In resource-limited settings where excisional procedures may be inaccessible, laser ablation\u0026rsquo;s logistical advantages (e.g., outpatient feasibility, minimal infrastructure) make it a valuable alternative, provided high-risk patients undergo close monitoring.\u003c/p\u003e\u003cp\u003eHowever, our study has limitations. The non-randomized design introduces potential selection bias, as the laser group had a higher proportion of high-grade squamous intraepithelial lesions (HSIL) on cytology (20.7% vs. 2.1% in the conization group). Additionally, the 6-month follow-up period limits our ability to assess long-term recurrence, which is critical given evidence of increasing ablation failure rates over time (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Future studies should incorporate extended follow-up and HPV subtyping post-treatment to differentiate between persistent infection and reinfection as causes of recurrence.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, CO₂ laser ablation may be a safe and effective treatment option for CIN2, particularly in younger patients with normal baseline cytology and a lower BMI. While conization remains the gold standard for high-risk or recurrent cases, laser therapy could offer a fertility-sparing alternative when combined with strict patient selection criteria and adherence to follow-up protocols. Further studies with longer follow-up durations are needed to confirm its comparative efficacy and long-term outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003cp\u003enot applicable.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eEthics Approval and Consent to Participate:\u003c/h2\u003e\u003cp\u003eThis study was approved by the Ethics Committee of Alborz University of Medical Sciences (Approval No.: IR.ABZUMS.REC.1403.354). All procedures performed were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments. Informed consent was obtained from all individual participants included in the study.\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eNo funding was received for conducting this study.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection, and surgical procedures were performed by S.M. Data analysis was conducted by M.S.A. The first draft of the manuscript was written by M.S.A. and all authors commented on previous versions. H.R. critically revised the work for important intellectual content. All authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTainio K, Athanasiou A, Tikkinen KA, Aaltonen R, C\u0026aacute;rdenas J, Glazer-Livson S et al (2018) Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance: systematic review and meta-analysis. BMJ. ;360\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOrganization WH (2019) WHO guidelines for the use of thermal ablation for cervical pre-cancer lesions. WHO guidelines for the use of thermal ablation for cervical pre-cancer lesions p. 56-\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePerkins RB, Guido RS, Castle PE, Chelmow D, Einstein MH, Garcia F et al (2020) 2019 ASCCP risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors. J Lower Genit Tract Dis 24(2):102\u0026ndash;131\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKyrgiou M, Athanasiou A, Paraskevaidi M, Mitra A, Kalliala I, Martin-Hirsch P et al (2016) Adverse obstetric outcomes after local treatment for cervical preinvasive and early invasive disease according to cone depth: systematic review and meta-analysis. BMJ. ;354\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBruinsma F, Quinn M (2011) The risk of preterm birth following treatment for precancerous changes in the cervix: a systematic review and meta-analysis. BJOG: Int J Obstet Gynecol 118(9):1031\u0026ndash;1041\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePerkins RB, Guido RS, Castle PE, Chelmow D, Einstein MH, Garcia F et al (2024) 2019 ASCCP risk-based management consensus guidelines: updates through 2023. J Lower Genit Tract Dis 28(1):3\u0026ndash;6\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSantesso N, Mustafa RA, Wiercioch W, Kehar R, Gandhi S, Chen Y et al (2016) Systematic reviews and meta-analyses of benefits and harms of cryotherapy, LEEP, and cold knife conization to treat cervical intraepithelial neoplasia. Int J Gynecol Obstet 132(3):266\u0026ndash;271\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eArbyn M, Redman CW, Verdoodt F, Kyrgiou M, Tzafetas M, Ghaem-Maghami S et al (2017) Incomplete excision of cervical precancer as a predictor of treatment failure: a systematic review and meta-analysis. Lancet Oncol 18(12):1665\u0026ndash;1679\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang L, Sauvaget C, Mosquera I, Basu P (2023) Efficacy, acceptability and safety of ablative versus excisional procedure in the treatment of histologically confirmed CIN2/3: A systematic review. BJOG: Int J Obstet Gynecol 130(2):153\u0026ndash;161\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKodama K, Yahata H, Okugawa K, Tomonobe H, Yasutake N, Yoshida S et al (2021) Prognostic outcomes and risk factors for recurrence after laser vaporization for cervical intraepithelial neoplasia: a single-center retrospective study. Int J Clin Oncol 26(4):770\u0026ndash;776\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMariya T, Nishikawa A, Umemoto M, Ogawa S, Saito T (2024) Impact of colposcopy-guided carbon dioxide laser vaporization therapy on peripheral cervical intraepithelial neoplasia lesions. Taiwan J Obstet Gynecol 63(6):846\u0026ndash;852\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFerrari F, Bonetti E, Oliveri G, Giannini A, Gozzini E, Conforti J et al (2024) Cold knife versus carbon dioxide for the treatment of preinvasive cervical lesion. Medicina 60(7):1056\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"lasers-in-medical-science","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"lims","sideBox":"Learn more about [Lasers in Medical Science](https://link.springer.com/journal/10103)","snPcode":"10103","submissionUrl":"https://submission.springernature.com/new-submission/10103/3","title":"Lasers in Medical Science","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Cervical Intraepithelial Neoplasia Grade 2, CO₂ Laser Ablation, Loop electrosurgical excision procedure","lastPublishedDoi":"10.21203/rs.3.rs-7670819/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7670819/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eThis study aimed to compare the efficacy of CO₂ laser ablation versus conization for treating cervical intraepithelial neoplasia grade 2 (CIN2) and to identify predictors of treatment failure.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA prospective observational cohort study was conducted on 146 women with histologically confirmed CIN2. Participants were allocated to either CO₂ laser ablation (n\u0026thinsp;=\u0026thinsp;100) or Loop electrosurgical excision procedure (LEEP, n\u0026thinsp;=\u0026thinsp;46) based on clinical decision. The primary outcome was histopathological treatment response (regression to CIN1/normal) at a 6-month follow-up. Propensity score matching was used to control for baseline confounders.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe overall treatment response rate was 81.5%, with no statistically significant difference between the conization (89.1%) and laser ablation (78.0%) groups (p\u0026thinsp;=\u0026thinsp;0.108). This non-significant difference persisted after propensity score matching (OR\u0026thinsp;=\u0026thinsp;0.66; 95% CI: 0.17 to 2.54; p\u0026thinsp;=\u0026thinsp;0.548). For the entire cohort, younger age and normal cytology were independent predictors of treatment success. In the laser group specifically, abnormal cytology, older age, and a BMI\u0026thinsp;\u0026ge;\u0026thinsp;25 were significant predictors of treatment failure.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eCO₂ laser ablation demonstrated comparable short-term efficacy to conization for managing CIN2. It represents a viable fertility-sparing alternative, particularly for younger patients with normal cytology and lower BMI. Careful patient selection is crucial for optimizing outcomes.\u003c/p\u003e","manuscriptTitle":"CO₂ Laser Ablation Versus Conization for Cervical Intraepithelial Neoplasia Grade 2: A Prospective Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-20 09:43:51","doi":"10.21203/rs.3.rs-7670819/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-05T22:04:34+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-21T08:29:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"53855120706946625642250881959095016721","date":"2025-12-18T19:57:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"186184378769590057321076168565853021325","date":"2025-12-15T23:01:17+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-08T00:39:25+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-08T00:38:45+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-29T07:11:25+00:00","index":"","fulltext":""},{"type":"submitted","content":"Lasers in Medical Science","date":"2025-09-22T09:11:21+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"lasers-in-medical-science","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"lims","sideBox":"Learn more about [Lasers in Medical Science](https://link.springer.com/journal/10103)","snPcode":"10103","submissionUrl":"https://submission.springernature.com/new-submission/10103/3","title":"Lasers in Medical Science","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"c7a1ec89-82f5-402b-8a1b-6435267018e3","owner":[],"postedDate":"October 20th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-03-25T02:24:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-20 09:43:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7670819","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7670819","identity":"rs-7670819","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}