Gastric-type adenocarcinoma of the uterine cervix from 2013 to 2023: Clinical characteristics and outcomes

Gastric-type adenocarcinoma of the uterine cervix from 2013 to 2023: Clinical characteristics and outcomes | 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 Gastric-type adenocarcinoma of the uterine cervix from 2013 to 2023: Clinical characteristics and outcomes Junwei Zhao, Zenghui Li, Haifeng Qiu, Jing Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5691976/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose To summarise our experience with gastric-type adenocarcinoma of the uterine cervix (GAS) at multiple cancer centres. Methods This retrospective study included patients diagnosed with GAS (from 1 June 2013 to 1 July 2023) from three collaborating institutions. Kaplan–Meier survival analysis was used to determine progression-free survival (PFS) and overall survival (OS). Results Among the 116 patients with GAS, 71 had negative human papillomavirus (HPV) genotyping results: ThinPrep cytologic test negative for intraepithelial lesion or malignancy in 45; atypical squamous cells of undetermined significance in 8; atypical squamous cells, which cannot exclude a high-grade squamous intraepithelial lesion, in 2; low-grade squamous intraepithelial lesion in 2; high-grade squamous intraepithelial lesion in 5; atypical glandular cell in 19; and adenocarcinoma in 3 patients. Most patients with GAS had advanced stage disease, with only 32.8% having stage I disease. The International Federation of Gynecology and Obstetrics stages were IB, II, III, and IV in 38, 11, 40, and 18 patients, respectively. The median PFS times for stage I and II–IV diseases were 74.9 and 61.3 months, respectively. The median OS times for patients with stage I and II–IV GAS were 109.7 and 87.6 months, respectively. The median PFS times were 74.9, 75.7, 60.3, and 12.8 months for stages I, II, III, and IV, respectively. Conclusion GAS is an aggressive form of cervical cancer with poor PFS and OS when diagnosed at stage II or higher. Human papillomavirus viruses neoplasm metastasis retrospective study uterine cervical neoplasms Figures Figure 1 Figure 2 Figure 3 Introduction Cervical carcinoma is the fourth most common cancer and the fourth leading cause of cancer death in women, with more than 600,000 cases and 300,000 deaths reported globally in 2020[ 1 ]. The incidence of endocervical adenocarcinoma is increasing continuously, accounting for around 25% of invasive cervical carcinoma cases[ 2 ]. Most cases of cervical cancer are related to human papillomavirus (HPV) infection, whereas only a few are unrelated types[ 3 ], for example, gastric-type adenocarcinoma of the uterine cervix (GAS), clear cell carcinoma, and mesonephric carcinoma. Among these, GAS, which was initially described by Kojima et al.[ 4 ],and constitutes approximately 10% of cervical adenocarcinoma[ 5 ], is the predominant HPV-unrelated subtype. GAS is recognized as a special type of cervical adenocarcinoma, with medical significance due to its lack of association with HPV infection, its invasive behaviour, its poorer clinical outcomes compared to usual endocervical adenocarcinoma (UEA), and its resistance to chemotherapy[ 6 ]. GAS is an aggressive treatment-resistant cancer and exhibits an aggressive nature with a significant level of malignancy. Its prognosis is poor due to its insidious development and tendency to progress towards the cervical canal. Moreover, the absence of specific tumour markers makes the early diagnosis of GAS challenging[ 7 ]. GAS shows aggressive behaviour accompanied by ominous histopathological predictors and a reduced survival rate. In order to comprehend the pathogenesis of GAS and identify potential therapeutic targets, it is imperative to explore the genetic traits and fundamental mechanisms that drive its pathogenicity. In this study, we characterised the clinical results of individuals with GAS from three cancer centres by placing emphasis not only on overall survival (OS) but also on additional clinical factors such as sites of metastasis and recurrence. Material and methods This study was approved by the institutional ethics committee of Yantai Yuhuangding Hospital (2022 − 414). Written informed consent was obtained from each patient or their authorized signatory. Patients diagnosed with GAS (from 1 June 2013 to 1 July 2023) from three collaborating institutions (The First Affiliated Hospital of Zhengzhou University, Henan Province, China; Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Henan Province, China; and Yantai Yuhuangding Hospital, Shandong Province, China) were included in this study. All patients with a pathological diagnosis of GAS were included. Exclusion criteria: 1) patients with a diagnosis of lobular endocervical glandular hyperplasia with the absence of invasive lesions; 2) for the sub-cohort analysis of progression-free survival (PFS) and OS, patients who were first diagnosed at the point of disease recurrence; and 3) complete clinical information unavailable. Demographic, pathological, and clinical information were collected and analysed. The staging of tumours was based on the International Federation of Gynecology and Obstetrics (FIGO) 2018 cervical cancer staging system. 8 If there was no primary surgical treatment, staging was determined by clinical manifestation and imaging diagnosis. The initial treatment was classified as surgery alone, ancillary therapy after surgery, simultaneous chemoradiotherapy (CCRT) with or without systematic chemotherapy, chemotherapy alone, CCRT with hysterectomy with or without ancillary chemotherapy, or palliative treatment. Information was also gathered with the respect of the recurrence of the disease, the site of recurrence, and the subsequent management. The Kaplan–Meier method was employed to analyse survival and log-rank tests were used for comparison. If the patients experienced no recurrence, PFS was defined as the interval from the diagnosis date to the last follow-up date, and the recurrence or progression of disease, or death were all defined as events. OS was censored from the date of diagnosis to the date of death or last follow-up if death had not occurred. Events were defined as mortality resulting from any cause. The final date of follow-up for the survival analysis was 1 July 2023. The comparison of survival curves was conducted using the log-rank test. Statistical analyses were performed with the Statistical Package for the Social Sciences software. Results Clinical and demographic characteristics A total of 116 patients (First Affiliated Hospital of Zhengzhou University, 88 patients; Affiliated Cancer Hospital of Zhengzhou University, 23 patients; and Yantai Yuhuangding Hospital, 5 patients) were initially identified for inclusion in this study. Follow-up information was only collected for 69 patients, as 47 patients were lost to follow-up. The stage at presentation was recorded in all but nine patients. All patients were diagnosed and evaluated based on cervical sampling (biopsy, curettage, loop electrocautery excision, hysterectomy, trachelectomy, exenteration). The demographic and tumour characteristics are presented in Table 1 . Table 1 Demographic and tumor characteristics of patients with gastric-type adenocarcinoma of the cervix at diagnosis (n = 116) n(%) Age, years , median(range) 50 (30–80) BMI , median(range) 24.12 (16–35) Tumor size <2cm 26(22) ≥ 2cm-<4cm 37(32) ≥ 4cm 25(22) Unknown 28(24) Lymphovascular space invasion Positive 30(26) Negative 30(26) Unknown 56(48) Lymph node metastasis Negative 62(53) pelvic 47(40) Abdominal 5(4) Unknown 2(2) Stage Stage I 38(33) Stage II 11(9) Stage III 40(34) Stage IV 18(16) Unknown 9(8) HPV Positive 11(10) Negative 71(61) Unknown 34(29) TCT NILM 45(39) ASCUS 8(7) ASC-H 2(2) LSIL 2(2) HSIL 5(4) AGC 19(16) AC 3(3) Unknow 33(28) The mean age at GAS diagnosis was 50 (range, 30–80) years, while the mean BMI was 24.12 (range, 16–35) kg/m 2 . The clinical manifestations included vaginal discharge (watery or bloody); pelvic pain; heavy bleeding (postcoital or irregular vaginal); and postmenopausal bleeding. Among the 116 patients with GAS, 71 (61.2%) had negative HPV genotyping results: ThinPrep cytologic test negative for intraepithelial lesion or malignancy in 45 patients (38.8%); atypical squamous cells of undetermined significance in 8 patients (6.9%); atypical squamous cells, which cannot exclude a high-grade squamous intraepithelial lesion, in 2 patients (1.7%); low-grade squamous intraepithelial lesion in 2 patients (1.7%); high-grade squamous intraepithelial lesion in 5 patients (4.3%); atypical glandular cell in 19 patients (16.4%); and adenocarcinoma in 3 patients (2.6%). Most patients with GAS presented at an advanced stage (II–IV [59.5%]), with only 32.8% presenting at stage I. The FIGO stages were IB, II, III, and IV in 38 (32.8%), 11 (9.5%), 40 (34.5%), and 18 (15.5%) patients, respectively. Other routinely evaluated pathological variables included lymphovascular invasion, regional and remote lymph node involvement, ovarian and fallopian tube metastases, pelvic and abdominal spread, and distant extraperitoneal spread. Notably, approximately 25.8% of patients had lymphovascular invasion, 40.5% had positive pelvic lymph nodes, and 4.3% had abdominal diseases. A total of 111 (95.7%) patients received the initial treatment. Treatments varied widely as patients presented with a range of disease stages (Table 2 ). Table 2 Treatment and outcomes for patients diagnosed with gastric-type adenocarcinoma N/total % Treatment Surgery alone 24/116 20.7 Surgery chemotherapy, radiation 30/116 25.9 Surgery, chemotherapy 30/116 25.9 Surgery, radiation 2/116 1.7 Chemotherapy, radiation 11116 9.5 Chemotherapy 7/116 6 None 12/116 10.3 Outcome Overall survival (months) 41(4-127) Progression-free survival (months) 30(2–98) Death 18 26.1 Recurrence 8 11.6 Living 43 62.3 In total, 38 (32.8%) patients presented with stage I disease. All but five patients underwent surgical resection and were treated with CCRT alone or chemotherapy. Fifteen patients underwent surgery followed by chemotherapy, and eight patients received CCRT. Eleven (9.5%) patients had stage II disease at presentation, of whom six underwent surgical treatment. Of these, two underwent surgery alone as their primary management. In total, 40 (34.5%) patients presented with stage III disease. Of these, 17 underwent surgical resection with CCRT. Eighteen (15.5%) patients presented with stage IV disease. Most patients (n = 9) received systemic therapy, including four who underwent additional surgical resection and received radiation. A total of 43 out of 69 (62.3%) patients showed no evidence of disease, 8/69 (11.6%) were alive with the disease, and 18/69 (26.1%) died of the disease. Survival outcomes The median follow-up time of the cohort was 59 (range, 13–1357) months. The median PFS and OS times were 69.2 (95% confidence interval [CI], 59.2–79.2) months, and 98.3 (95% CI, 86.5–110.1) months, respectively (Fig. 1 ). The median PFS times were 74.9 (95% CI, 64.0–89.7) months and 61.3 (95% CI, 49.0–73.6; p = 0.054) months for stage I and stage II–IV disease, respectively (Fig. 2 ). The median OS times for patients with stage I and II–IV GAS were 109.7 (95% CI, 95.8–123.6) and 87.6 (95% CI, 71.3–103.9) months (p = 0.044), respectively. According to the disease stage (Fig. 3 ), the median PFS times were 74.9 (95% CI, 64.0–89.7), 75.7 (95% CI, 62.1–89.3), 60.3 (95% CI, 44.0–76.7), and 12.8 (95% CI, 8.8–16.8) months for stages I, II, III, and IV, respectively (p = 0.001). According to the disease stage, the median OS times were 109.7 (95% CI, 95.8–123.6), 74.8 (95% CI, 60.2–89.4), 76.0 (95% CI, 57.9–94.0), and 103.1 (95% CI, 78.1–128.2) months for stages I, II, III, and IV, respectively (p = 0.143, Fig. 3 ). Discussion Adenocarcinomas of the cervix account for approximately 20–25% of cervical carcinomas, of which, 80–90% are associated with HPV infection, and the remaining cases are non-HPV-associated[ 1 ]. GAS is a rare form of cervical cancer which is not related to HPV infection[ 8 ]. It is an invasive type of cervical cancer with a poor survival rate beyond stage I. The current study showed that more than half of the patients were diagnosed with stage II cervical cancer or higher. The median PFS and OS times for patients with stage I GAS were 107 (95% CI, 14.8–199.2) and 111 (95% CI, 17–205.1) months, respectively, whereas those for patients with stages II–IV were 17 (95% CI, 5.6–28.4) and 33 (95% CI, 28.2–37.8) months. These results aligns with those of a previous retrospective study[ 9 ]. The median age of patients diagnosed with GAS in our study was 50 years, similar to the findings of Stolnicu et al, who reported a median age of 55 years at GAS diagnosis[ 5 ]. Our data confirm that only 38% of patients were diagnosed at stage I, which aligns closely with the 41% reported by Karamurzin et al[ 10 ]. The use of cytology to diagnose late-stage GAS can present challenges, frequently leading to misdiagnosis; the identification of these lesions relies solely on high-risk HPV testing. GAS is usually diagnosed at a more advanced stage than HPV-associated UEA, thus indicating that the former remains more aggressive than the latter.[ 7 ] In this study, the proportion of patients diagnosed with GAS markedly increased as the disease progressed. This finding suggests that GAS may be associated with poorer outcomes in patients with early-stage cancer. A previous study reported a notably poorer five-year disease-specific survival for GAS than for non-gastric-type adenocarcinomas (30% vs. 77%)[ 11 ]. Similarly, Karamurzin et al found the five-year disease-specific survival rates for GAS and HPV-related adenocarcinomas were 42% and 91%, respectively[ 12 ]. Irrespective of the degree of differentiation and nuclear atypia, all GAS cases exhibit aggressive behaviour; usually present at a later stage compared to HPV-associated adenocarcinoma; and tend to spread to unusual sites, including the peritoneum, omentum, adnexa, liver, brain, and bone[ 13 ]. In recurrent patients (11.6%), the majority experienced pelvic local recurrence. The recurrence rate was consistently at 40%, with 50–60% of cases involving pelvic recurrence[ 14 ]; furthermore, most of these cases occurred in the first year after the completion of prior treatment. The treatment of local recurrence is challenging because GAS may be less sensitive to radioactivity than other types of cancer. A retrospective study showed that patients with GAS were less sensitive to radiotherapy than patients with UEA[ 2 ]. In a phase II study, the pathological response rate of GAS to neoadjuvant chemotherapy with carboplatin and docetaxel was significantly lower than that of UEA, and the survival outcomes were also worse[ 15 ]. The response to chemotherapy in advanced or recurrent GAS has not been systematically evaluated, and further studies are required to improve the treatment of this rare tumour. Given the low sensitivity of GAS to chemotherapy and radiotherapy, the identification of potential molecular targets may provide new therapeutic approaches for treating patients with GAS. GAS is usually diagnosed at an advanced stage and generally has poor outcomes. The poor prognosis may be associated with the high ovarian metastasis rate of patients with GAS. Given the widespread adoption of HPV vaccination, GAS may account for a greater proportion of newly diagnosed cases of cervical cancers in the future. Owing to the genomic and histological similarities between GAS and gastrointestinal malignancies, further research should be conducted on the optimal treatment of GAS, including surgery, chemotherapy, and radiotherapy. Finally, cancer registration for these rare tumours may lead to the development of reliable practice guidelines. Declarations Ethics approval and consent to participate Individual informed consent had been collected from all study participants. This study received ethical approval from the Institutional Review Board of our hospital(2022 − 414). All experiments were performed in accordance with relevant guidelines and regulations. Conflict of interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Abbreviations HPV, human papillomavirus; TCT, ThinPrep cytologic test; NILM, negative for intraepithelial lesion or malignancy; ASCUS, atypical squamous cells of undetermined significance; ASC-H, atypical squamous cells, cannot exclude a high-grade squamous intraepithelial lesion; LSIL, low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion; AGC, atypical glandular cell; AC, adenocarcinoma. Funding This study was supported by the Yantai Science and Technology Plan (2022YD011) and the Natural Foundation of Shandong Province (ZR2021QH124). Author Contribution Jing Wang designed this study. Haifeng Qiu collected and analyzed the data. Junwei Zhao participated in writing the original draft. Zenghui Li and Jing Wang reviewed and revised the manuscript. All authors contributed to the article and approved the submitted version.Funding This study was supported by the Yantai Science and Technology Plan (2022YD011) and the Natural Foundation of Shandong Province (ZR2021QH124). AcknowledgementsNone acknowledged. Acknowledgement None acknowledged. Availability of Data and Materials All data generated in this published article and supplementary information files for further data are available from the corresponding author. References Radomska A, Lee D, Neufeld H, Korte N, Torlakovic E, Agrawal A, et al. A retrospective study on incidence, diagnosis, and clinical outcome of gastric-type endocervical adenocarcinoma in a single institution. Diagn Pathol. 2021;16:68. Park E, Kim SW, Kim S, Kim HS, Lee JY, Kim YT, et al. Genetic characteristics of gastric-type mucinous carcinoma of the uterine cervix. Mod Pathol. 2021;34:637–46. Kuruma A, Kodama M, Hori Y, Sato K, Fujii M, Isohashi F et al. Gastric-Type Adenocarcinoma of the Uterine Cervix Associated with Poor Response to Definitive Radiotherapy. Cancers (Basel). 2022; 15. Kojima A, Mikami Y, Sudo T, Yamaguchi S, Kusanagi Y, Ito M, et al. Gastric morphology and immunophenotype predict poor outcome in mucinous adenocarcinoma of the uterine cervix. Am J Surg Pathol. 2007;31:664–72. Stolnicu S, Barsan I, Hoang L, Patel P, Terinte C, Pesci A, et al. International Endocervical Adenocarcinoma Criteria and Classification (IECC): A New Pathogenetic Classification for Invasive Adenocarcinomas of the Endocervix. Am J Surg Pathol. 2018;42:214–26. Park KJ. Cervical adenocarcinoma: integration of HPV status, pattern of invasion, morphology and molecular markers into classification. Histopathology. 2020;76:112–27. Nishio S, Mikami Y, Tokunaga H, Yaegashi N, Satoh T, Saito M, et al. Analysis of gastric-type mucinous carcinoma of the uterine cervix - An aggressive tumor with a poor prognosis: A multi-institutional study. Gynecol Oncol. 2019;153:13–9. Gordhandas SB, Kahn R, Sassine D, Aviki EM, Baltich Nelson B, Catchings A, et al. Gastric-type adenocarcinoma of the cervix in patients with Peutz-Jeghers syndrome: a systematic review of the literature with proposed screening guidelines. Int J Gynecol Cancer. 2022;32:79–88. Ehmann S, Sassine D, Straubhar AM, Praiss AM, Aghajanian C, Alektiar KM, et al. Gastric-type adenocarcinoma of the cervix: Clinical outcomes and genomic drivers. Gynecol Oncol. 2022;167:458–66. Karamurzin YS, Kiyokawa T, Parkash V, Jotwani AR, Patel P, Pike MC, et al. Gastric-type Endocervical Adenocarcinoma: An Aggressive Tumor With Unusual Metastatic Patterns and Poor Prognosis. Am J Surg Pathol. 2015;39:1449–57. Nara M, Hashi A, Murata S, Kondo T, Yuminamochi T, Nakazawa K, et al. Lobular endocervical glandular hyperplasia as a presumed precursor of cervical adenocarcinoma independent of human papillomavirus infection. Gynecol Oncol. 2007;106:289–98. Greenland NY, Wolsky RJ, Darragh TM, Vohra P. Gastric-type endocervical adenocarcinoma and cervical cytology: Experience at a general hospital and review of the literature. Cytopathology. 2021;32:75–83. Mikami Y, McCluggage WG. Endocervical glandular lesions exhibiting gastric differentiation: an emerging spectrum of benign, premalignant, and malignant lesions. Adv Anat Pathol. 2013;20:227–37. Nishio S, Matsuo K, Nasu H, Murotani K, Mikami Y, Yaegashi N, et al. Analysis of postoperative adjuvant therapy in 102 patients with gastric-type mucinous carcinoma of the uterine cervix: A multi-institutional study. Eur J Surg Oncol. 2022;48:2039–44. Kojima A, Shimada M, Mikami Y, Nagao S, Takeshima N, Sugiyama T, et al. Chemoresistance of Gastric-Type Mucinous Carcinoma of the Uterine Cervix: A Study of the Sankai Gynecology Study Group. Int J Gynecol Cancer. 2018;28:99–106. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-5691976","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":395830257,"identity":"248518b2-7615-4b33-bc7b-df48118942b5","order_by":0,"name":"Junwei Zhao","email":"","orcid":"","institution":"Yantai Yuhuangding Hospital Affiliated to Medical College of Qingdao University","correspondingAuthor":false,"prefix":"","firstName":"Junwei","middleName":"","lastName":"Zhao","suffix":""},{"id":395830258,"identity":"b8433adb-4ce4-4acb-ac48-d62ffb96775d","order_by":1,"name":"Zenghui Li","email":"","orcid":"","institution":"Yantai Yuhuangding 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Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwElEQVRIiWNgGAWjYBACfvnHBw5IVPyX4ydai2RDWuIDizPMxpINxGoxOJBjbFDZwpy44QDxtpwxk7jZwGZsfDx5A8OPim2EtfAztpVJztzBI2d25lkBY8+Z20TY0sy8TVryjISx2Y0cA2bGNiK0GBxjMJP+22aQuHkG0VrOsBgbSLYlJG6QIFaL5Ay2xAcSZw4YSwD9cpAov/BLMIOi8oAcf3vyxgc/KojQggQSDA6QpB6shVQdo2AUjIJRMEIAAJWzQEHkuFnRAAAAAElFTkSuQmCC","orcid":"","institution":"Yantai Yuhuangding Hospital Affiliated to Medical College of Qingdao University","correspondingAuthor":true,"prefix":"","firstName":"Jing","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2024-12-22 04:08:05","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5691976/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5691976/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":72755982,"identity":"d05e0095-40b4-4462-96d7-0c84f1935969","added_by":"auto","created_at":"2025-01-01 17:01:27","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":21818,"visible":true,"origin":"","legend":"\u003cp\u003e(A) overall survival (OS) and (B) progression-free survival (PFS) for patients with gastric-type adenocarcinoma of the uterine cervix.\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5691976/v1/3b510c3458edb2e6eb838431.jpg"},{"id":72755069,"identity":"cd09c65f-818c-447d-b2b6-0cca2a9243ae","added_by":"auto","created_at":"2025-01-01 16:53:24","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":24705,"visible":true,"origin":"","legend":"\u003cp\u003e(A) overall survival (OS) and (B) progression-free survival (PFS) for stage I vs. stage II–IV gastric-type adenocarcinoma of the uterine cervix.\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5691976/v1/d62c0a532dced918afa2de4c.jpg"},{"id":72755983,"identity":"4e5e5803-854a-4ffa-8939-e047e2ec5bc1","added_by":"auto","created_at":"2025-01-01 17:01:27","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":41209,"visible":true,"origin":"","legend":"\u003cp\u003e(A) overall survival (OS) and progression-free survival (PFS) for patients with gastric-type adenocarcinoma of the uterine cervix according to stage.\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5691976/v1/2c43dfe14e9ea86846f087b1.jpg"},{"id":77917749,"identity":"03ed7011-1856-405c-a9cc-513ed5eee21b","added_by":"auto","created_at":"2025-03-06 20:31:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":612679,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5691976/v1/83cdfa4e-2abd-46e5-bd7a-3b787f2d7159.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Gastric-type adenocarcinoma of the uterine cervix from 2013 to 2023: Clinical characteristics and outcomes","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCervical carcinoma is the fourth most common cancer and the fourth leading cause of cancer death in women, with more than 600,000 cases and 300,000 deaths reported globally in 2020[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The incidence of endocervical adenocarcinoma is increasing continuously, accounting for around 25% of invasive cervical carcinoma cases[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Most cases of cervical cancer are related to human papillomavirus (HPV) infection, whereas only a few are unrelated types[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], for example, gastric-type adenocarcinoma of the uterine cervix (GAS), clear cell carcinoma, and mesonephric carcinoma. Among these, GAS, which was initially described by Kojima et al.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e],and constitutes approximately 10% of cervical adenocarcinoma[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], is the predominant HPV-unrelated subtype. GAS is recognized as a special type of cervical adenocarcinoma, with medical significance due to its lack of association with HPV infection, its invasive behaviour, its poorer clinical outcomes compared to usual endocervical adenocarcinoma (UEA), and its resistance to chemotherapy[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. GAS is an aggressive treatment-resistant cancer and exhibits an aggressive nature with a significant level of malignancy. Its prognosis is poor due to its insidious development and tendency to progress towards the cervical canal. Moreover, the absence of specific tumour markers makes the early diagnosis of GAS challenging[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGAS shows aggressive behaviour accompanied by ominous histopathological predictors and a reduced survival rate. In order to comprehend the pathogenesis of GAS and identify potential therapeutic targets, it is imperative to explore the genetic traits and fundamental mechanisms that drive its pathogenicity. In this study, we characterised the clinical results of individuals with GAS from three cancer centres by placing emphasis not only on overall survival (OS) but also on additional clinical factors such as sites of metastasis and recurrence.\u003c/p\u003e"},{"header":"Material and methods","content":"\u003cp\u003e This study was approved by the institutional ethics committee of Yantai Yuhuangding Hospital (2022\u0026thinsp;\u0026minus;\u0026thinsp;414). Written informed consent was obtained from each patient or their authorized signatory. Patients diagnosed with GAS (from 1 June 2013 to 1 July 2023) from three collaborating institutions (The First Affiliated Hospital of Zhengzhou University, Henan Province, China; Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Henan Province, China; and Yantai Yuhuangding Hospital, Shandong Province, China) were included in this study. All patients with a pathological diagnosis of GAS were included. Exclusion criteria: 1) patients with a diagnosis of lobular endocervical glandular hyperplasia with the absence of invasive lesions; 2) for the sub-cohort analysis of progression-free survival (PFS) and OS, patients who were first diagnosed at the point of disease recurrence; and 3) complete clinical information unavailable.\u003c/p\u003e \u003cp\u003eDemographic, pathological, and clinical information were collected and analysed. The staging of tumours was based on the International Federation of Gynecology and Obstetrics (FIGO) 2018 cervical cancer staging system.\u003csup\u003e8\u003c/sup\u003e If there was no primary surgical treatment, staging was determined by clinical manifestation and imaging diagnosis. The initial treatment was classified as surgery alone, ancillary therapy after surgery, simultaneous chemoradiotherapy (CCRT) with or without systematic chemotherapy, chemotherapy alone, CCRT with hysterectomy with or without ancillary chemotherapy, or palliative treatment. Information was also gathered with the respect of the recurrence of the disease, the site of recurrence, and the subsequent management.\u003c/p\u003e \u003cp\u003eThe Kaplan\u0026ndash;Meier method was employed to analyse survival and log-rank tests were used for comparison. If the patients experienced no recurrence, PFS was defined as the interval from the diagnosis date to the last follow-up date, and the recurrence or progression of disease, or death were all defined as events. OS was censored from the date of diagnosis to the date of death or last follow-up if death had not occurred. Events were defined as mortality resulting from any cause. The final date of follow-up for the survival analysis was 1 July 2023. The comparison of survival curves was conducted using the log-rank test. Statistical analyses were performed with the Statistical Package for the Social Sciences software.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eClinical and demographic characteristics\u003c/h2\u003e \u003cp\u003eA total of 116 patients (First Affiliated Hospital of Zhengzhou University, 88 patients; Affiliated Cancer Hospital of Zhengzhou University, 23 patients; and Yantai Yuhuangding Hospital, 5 patients) were initially identified for inclusion in this study. Follow-up information was only collected for 69 patients, as 47 patients were lost to follow-up. The stage at presentation was recorded in all but nine patients. All patients were diagnosed and evaluated based on cervical sampling (biopsy, curettage, loop electrocautery excision, hysterectomy, trachelectomy, exenteration). The demographic and tumour characteristics are presented in 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\u003eDemographic and tumor characteristics of patients with gastric-type adenocarcinoma of the cervix at diagnosis (n\u0026thinsp;=\u0026thinsp;116)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en(%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge, years\u003c/b\u003e, median(range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50\u003c/p\u003e \u003cp\u003e(30\u0026ndash;80)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI\u003c/b\u003e, median(range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.12\u003c/p\u003e \u003cp\u003e(16\u0026ndash;35)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTumor size\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;2cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26(22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;2cm-\u0026lt;4cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37(32)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;4cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25(22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28(24)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLymphovascular space invasion\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30(26)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30(26)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56(48)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLymph node metastasis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62(53)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epelvic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47(40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbdominal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38(33)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40(34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18(16)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHPV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71(61)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34(29)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNILM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45(39)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASCUS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASC-H\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAGC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19(16)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33(28)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe mean age at GAS diagnosis was 50 (range, 30\u0026ndash;80) years, while the mean BMI was 24.12 (range, 16\u0026ndash;35) kg/m\u003csup\u003e2\u003c/sup\u003e. The clinical manifestations included vaginal discharge (watery or bloody); pelvic pain; heavy bleeding (postcoital or irregular vaginal); and postmenopausal bleeding. Among the 116 patients with GAS, 71 (61.2%) had negative HPV genotyping results: ThinPrep cytologic test negative for intraepithelial lesion or malignancy in 45 patients (38.8%); atypical squamous cells of undetermined significance in 8 patients (6.9%); atypical squamous cells, which cannot exclude a high-grade squamous intraepithelial lesion, in 2 patients (1.7%); low-grade squamous intraepithelial lesion in 2 patients (1.7%); high-grade squamous intraepithelial lesion in 5 patients (4.3%); atypical glandular cell in 19 patients (16.4%); and adenocarcinoma in 3 patients (2.6%). Most patients with GAS presented at an advanced stage (II\u0026ndash;IV [59.5%]), with only 32.8% presenting at stage I. The FIGO stages were IB, II, III, and IV in 38 (32.8%), 11 (9.5%), 40 (34.5%), and 18 (15.5%) patients, respectively. Other routinely evaluated pathological variables included lymphovascular invasion, regional and remote lymph node involvement, ovarian and fallopian tube metastases, pelvic and abdominal spread, and distant extraperitoneal spread. Notably, approximately 25.8% of patients had lymphovascular invasion, 40.5% had positive pelvic lymph nodes, and 4.3% had abdominal diseases. A total of 111 (95.7%) patients received the initial treatment. Treatments varied widely as patients presented with a range of disease stages (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\u003eTreatment and outcomes for patients diagnosed with gastric-type adenocarcinoma\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\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN/total\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTreatment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery alone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24/116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery chemotherapy, radiation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30/116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery, chemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30/116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery, radiation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy, radiation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7/116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12/116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOutcome\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOverall survival (months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41(4-127)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProgression-free survival (months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30(2\u0026ndash;98)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecurrence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiving\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn total, 38 (32.8%) patients presented with stage I disease. All but five patients underwent surgical resection and were treated with CCRT alone or chemotherapy. Fifteen patients underwent surgery followed by chemotherapy, and eight patients received CCRT. Eleven (9.5%) patients had stage II disease at presentation, of whom six underwent surgical treatment. Of these, two underwent surgery alone as their primary management. In total, 40 (34.5%) patients presented with stage III disease. Of these, 17 underwent surgical resection with CCRT. Eighteen (15.5%) patients presented with stage IV disease. Most patients (n\u0026thinsp;=\u0026thinsp;9) received systemic therapy, including four who underwent additional surgical resection and received radiation. A total of 43 out of 69 (62.3%) patients showed no evidence of disease, 8/69 (11.6%) were alive with the disease, and 18/69 (26.1%) died of the disease.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSurvival outcomes\u003c/h3\u003e\n\u003cp\u003eThe median follow-up time of the cohort was 59 (range, 13\u0026ndash;1357) months. The median PFS and OS times were 69.2 (95% confidence interval [CI], 59.2\u0026ndash;79.2) months, and 98.3 (95% CI, 86.5\u0026ndash;110.1) months, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The median PFS times were 74.9 (95% CI, 64.0\u0026ndash;89.7) months and 61.3 (95% CI, 49.0\u0026ndash;73.6; p\u0026thinsp;=\u0026thinsp;0.054) months for stage I and stage II\u0026ndash;IV disease, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The median OS times for patients with stage I and II\u0026ndash;IV GAS were 109.7 (95% CI, 95.8\u0026ndash;123.6) and 87.6 (95% CI, 71.3\u0026ndash;103.9) months (p\u0026thinsp;=\u0026thinsp;0.044), respectively. According to the disease stage (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), the median PFS times were 74.9 (95% CI, 64.0\u0026ndash;89.7), 75.7 (95% CI, 62.1\u0026ndash;89.3), 60.3 (95% CI, 44.0\u0026ndash;76.7), and 12.8 (95% CI, 8.8\u0026ndash;16.8) months for stages I, II, III, and IV, respectively (p\u0026thinsp;=\u0026thinsp;0.001). According to the disease stage, the median OS times were 109.7 (95% CI, 95.8\u0026ndash;123.6), 74.8 (95% CI, 60.2\u0026ndash;89.4), 76.0 (95% CI, 57.9\u0026ndash;94.0), and 103.1 (95% CI, 78.1\u0026ndash;128.2) months for stages I, II, III, and IV, respectively (p\u0026thinsp;=\u0026thinsp;0.143, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAdenocarcinomas of the cervix account for approximately 20\u0026ndash;25% of cervical carcinomas, of which, 80\u0026ndash;90% are associated with HPV infection, and the remaining cases are non-HPV-associated[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. GAS is a rare form of cervical cancer which is not related to HPV infection[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. It is an invasive type of cervical cancer with a poor survival rate beyond stage I. The current study showed that more than half of the patients were diagnosed with stage II cervical cancer or higher. The median PFS and OS times for patients with stage I GAS were 107 (95% CI, 14.8\u0026ndash;199.2) and 111 (95% CI, 17\u0026ndash;205.1) months, respectively, whereas those for patients with stages II\u0026ndash;IV were 17 (95% CI, 5.6\u0026ndash;28.4) and 33 (95% CI, 28.2\u0026ndash;37.8) months. These results aligns with those of a previous retrospective study[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The median age of patients diagnosed with GAS in our study was 50 years, similar to the findings of Stolnicu et al, who reported a median age of 55 years at GAS diagnosis[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Our data confirm that only 38% of patients were diagnosed at stage I, which aligns closely with the 41% reported by Karamurzin et al[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The use of cytology to diagnose late-stage GAS can present challenges, frequently leading to misdiagnosis; the identification of these lesions relies solely on high-risk HPV testing. GAS is usually diagnosed at a more advanced stage than HPV-associated UEA, thus indicating that the former remains more aggressive than the latter.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] In this study, the proportion of patients diagnosed with GAS markedly increased as the disease progressed. This finding suggests that GAS may be associated with poorer outcomes in patients with early-stage cancer.\u003c/p\u003e \u003cp\u003eA previous study reported a notably poorer five-year disease-specific survival for GAS than for non-gastric-type adenocarcinomas (30% vs. 77%)[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Similarly, Karamurzin et al found the five-year disease-specific survival rates for GAS and HPV-related adenocarcinomas were 42% and 91%, respectively[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Irrespective of the degree of differentiation and nuclear atypia, all GAS cases exhibit aggressive behaviour; usually present at a later stage compared to HPV-associated adenocarcinoma; and tend to spread to unusual sites, including the peritoneum, omentum, adnexa, liver, brain, and bone[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In recurrent patients (11.6%), the majority experienced pelvic local recurrence. The recurrence rate was consistently at 40%, with 50\u0026ndash;60% of cases involving pelvic recurrence[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]; furthermore, most of these cases occurred in the first year after the completion of prior treatment. The treatment of local recurrence is challenging because GAS may be less sensitive to radioactivity than other types of cancer. A retrospective study showed that patients with GAS were less sensitive to radiotherapy than patients with UEA[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In a phase II study, the pathological response rate of GAS to neoadjuvant chemotherapy with carboplatin and docetaxel was significantly lower than that of UEA, and the survival outcomes were also worse[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The response to chemotherapy in advanced or recurrent GAS has not been systematically evaluated, and further studies are required to improve the treatment of this rare tumour. Given the low sensitivity of GAS to chemotherapy and radiotherapy, the identification of potential molecular targets may provide new therapeutic approaches for treating patients with GAS.\u003c/p\u003e \u003cp\u003eGAS is usually diagnosed at an advanced stage and generally has poor outcomes. The poor prognosis may be associated with the high ovarian metastasis rate of patients with GAS. Given the widespread adoption of HPV vaccination, GAS may account for a greater proportion of newly diagnosed cases of cervical cancers in the future. Owing to the genomic and histological similarities between GAS and gastrointestinal malignancies, further research should be conducted on the optimal treatment of GAS, including surgery, chemotherapy, and radiotherapy. Finally, cancer registration for these rare tumours may lead to the development of reliable practice guidelines.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e \u003cp\u003e Individual informed consent had been collected from all study participants. This study received ethical approval from the Institutional Review Board of our hospital(2022\u0026thinsp;\u0026minus;\u0026thinsp;414). All experiments were performed in accordance with relevant guidelines and regulations.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eConflict of interest\u003c/h2\u003e \u003cp\u003eThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eAbbreviations\u003c/h2\u003e \u003cp\u003eHPV, human papillomavirus; TCT, ThinPrep cytologic test; NILM, negative for intraepithelial lesion or malignancy; ASCUS, atypical squamous cells of undetermined significance; ASC-H, atypical squamous cells, cannot exclude a high-grade squamous intraepithelial lesion; LSIL, low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion; AGC, atypical glandular cell; AC, adenocarcinoma.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis study was supported by the Yantai Science and Technology Plan (2022YD011) and the Natural Foundation of Shandong Province (ZR2021QH124).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eJing Wang designed this study. Haifeng Qiu collected and analyzed the data. Junwei Zhao participated in writing the original draft. Zenghui Li and Jing Wang reviewed and revised the manuscript. All authors contributed to the article and approved the submitted version.Funding This study was supported by the Yantai Science and Technology Plan (2022YD011) and the Natural Foundation of Shandong Province (ZR2021QH124). AcknowledgementsNone acknowledged.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eNone acknowledged.\u003c/p\u003e\u003ch2\u003eAvailability of Data and Materials\u003c/h2\u003e \u003cp\u003eAll data generated in this published article and supplementary information files for further data are available from the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRadomska A, Lee D, Neufeld H, Korte N, Torlakovic E, Agrawal A, et al. A retrospective study on incidence, diagnosis, and clinical outcome of gastric-type endocervical adenocarcinoma in a single institution. Diagn Pathol. 2021;16:68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark E, Kim SW, Kim S, Kim HS, Lee JY, Kim YT, et al. Genetic characteristics of gastric-type mucinous carcinoma of the uterine cervix. Mod Pathol. 2021;34:637\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKuruma A, Kodama M, Hori Y, Sato K, Fujii M, Isohashi F et al. Gastric-Type Adenocarcinoma of the Uterine Cervix Associated with Poor Response to Definitive Radiotherapy. Cancers (Basel). 2022; 15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKojima A, Mikami Y, Sudo T, Yamaguchi S, Kusanagi Y, Ito M, et al. Gastric morphology and immunophenotype predict poor outcome in mucinous adenocarcinoma of the uterine cervix. Am J Surg Pathol. 2007;31:664\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStolnicu S, Barsan I, Hoang L, Patel P, Terinte C, Pesci A, et al. International Endocervical Adenocarcinoma Criteria and Classification (IECC): A New Pathogenetic Classification for Invasive Adenocarcinomas of the Endocervix. Am J Surg Pathol. 2018;42:214\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark KJ. Cervical adenocarcinoma: integration of HPV status, pattern of invasion, morphology and molecular markers into classification. Histopathology. 2020;76:112\u0026ndash;27.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNishio S, Mikami Y, Tokunaga H, Yaegashi N, Satoh T, Saito M, et al. Analysis of gastric-type mucinous carcinoma of the uterine cervix - An aggressive tumor with a poor prognosis: A multi-institutional study. Gynecol Oncol. 2019;153:13\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGordhandas SB, Kahn R, Sassine D, Aviki EM, Baltich Nelson B, Catchings A, et al. Gastric-type adenocarcinoma of the cervix in patients with Peutz-Jeghers syndrome: a systematic review of the literature with proposed screening guidelines. Int J Gynecol Cancer. 2022;32:79\u0026ndash;88.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEhmann S, Sassine D, Straubhar AM, Praiss AM, Aghajanian C, Alektiar KM, et al. Gastric-type adenocarcinoma of the cervix: Clinical outcomes and genomic drivers. Gynecol Oncol. 2022;167:458\u0026ndash;66.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaramurzin YS, Kiyokawa T, Parkash V, Jotwani AR, Patel P, Pike MC, et al. Gastric-type Endocervical Adenocarcinoma: An Aggressive Tumor With Unusual Metastatic Patterns and Poor Prognosis. Am J Surg Pathol. 2015;39:1449\u0026ndash;57.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNara M, Hashi A, Murata S, Kondo T, Yuminamochi T, Nakazawa K, et al. Lobular endocervical glandular hyperplasia as a presumed precursor of cervical adenocarcinoma independent of human papillomavirus infection. Gynecol Oncol. 2007;106:289\u0026ndash;98.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGreenland NY, Wolsky RJ, Darragh TM, Vohra P. Gastric-type endocervical adenocarcinoma and cervical cytology: Experience at a general hospital and review of the literature. Cytopathology. 2021;32:75\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMikami Y, McCluggage WG. Endocervical glandular lesions exhibiting gastric differentiation: an emerging spectrum of benign, premalignant, and malignant lesions. Adv Anat Pathol. 2013;20:227\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNishio S, Matsuo K, Nasu H, Murotani K, Mikami Y, Yaegashi N, et al. Analysis of postoperative adjuvant therapy in 102 patients with gastric-type mucinous carcinoma of the uterine cervix: A multi-institutional study. Eur J Surg Oncol. 2022;48:2039\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKojima A, Shimada M, Mikami Y, Nagao S, Takeshima N, Sugiyama T, et al. Chemoresistance of Gastric-Type Mucinous Carcinoma of the Uterine Cervix: A Study of the Sankai Gynecology Study Group. Int J Gynecol Cancer. 2018;28:99\u0026ndash;106.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Human papillomavirus viruses, neoplasm metastasis, retrospective study, uterine cervical neoplasms","lastPublishedDoi":"10.21203/rs.3.rs-5691976/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5691976/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTo summarise our experience with gastric-type adenocarcinoma of the uterine cervix (GAS) at multiple cancer centres.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective study included patients diagnosed with GAS (from 1 June 2013 to 1 July 2023) from three collaborating institutions. Kaplan\u0026ndash;Meier survival analysis was used to determine progression-free survival (PFS) and overall survival (OS).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong the 116 patients with GAS, 71 had negative human papillomavirus (HPV) genotyping results: ThinPrep cytologic test negative for intraepithelial lesion or malignancy in 45; atypical squamous cells of undetermined significance in 8; atypical squamous cells, which cannot exclude a high-grade squamous intraepithelial lesion, in 2; low-grade squamous intraepithelial lesion in 2; high-grade squamous intraepithelial lesion in 5; atypical glandular cell in 19; and adenocarcinoma in 3 patients. Most patients with GAS had advanced stage disease, with only 32.8% having stage I disease. The International Federation of Gynecology and Obstetrics stages were IB, II, III, and IV in 38, 11, 40, and 18 patients, respectively. The median PFS times for stage I and II\u0026ndash;IV diseases were 74.9 and 61.3 months, respectively. The median OS times for patients with stage I and II\u0026ndash;IV GAS were 109.7 and 87.6 months, respectively. The median PFS times were 74.9, 75.7, 60.3, and 12.8 months for stages I, II, III, and IV, respectively.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eGAS is an aggressive form of cervical cancer with poor PFS and OS when diagnosed at stage II or higher.\u003c/p\u003e","manuscriptTitle":"Gastric-type adenocarcinoma of the uterine cervix from 2013 to 2023: Clinical characteristics and outcomes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-01 16:53:14","doi":"10.21203/rs.3.rs-5691976/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"641b5240-d3f4-420a-b747-15dcd3b281db","owner":[],"postedDate":"January 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-03-06T20:23:17+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-01 16:53:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5691976","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5691976","identity":"rs-5691976","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}