Surgical resection outperforms chemoradiation in HPV-associated mucinous adenocarcinoma of the cervix: a SEER-based survival analysis

Objective: Given the rarity of human papillomavirus-associated mucinous adenocarcinoma (HPVAM) of the cervix and the lack of established clinical treatment guidelines, there is uncertainty regarding optimal clinical management. This study utilized population-based cancer registry data to investigate the clinical characteristics, treatment patterns, and prognostic factors of HPVAM. Methods: Patients diagnosed with HPVAM and usual-type endocervical adenocarcinoma (UEA) between 2000 and 2021 were identified from the Surveillance, Epidemiology, and End Results (SEER)database. Comparisons utilized Chi-square tests, log-rank tests, Kaplan-Meier survival analysis, Cox regression analyses, competing risks analysis, Gray’s tests and subgroup analyses. Propensity score matching (PSM) (1:4) was performed to reduce confounding bias using variables with significant pre-matching differences (P<0.05) and an optimal matching algorithm. Results: The retrospective cohort included 6459 UEA and 590 HPVAM patients. Compared to UEA patients, HPVAM patients exhibited larger tumors (>4 cm), more advanced stages, and higher rates of lymph node metastasis and distant metastasis. The1-, 3-, and 5-year cumulative overall survival (OS) rates for HPVAM patients were 89.60% (95%CI: 87.14-92.13%), 74.81% (95%CI: 71.29-78.51%), and 66.10% (95%CI: 62.20-70.25%). These rates were significantly lower than those for UEA patients, which were 92.71% (95%CI: 92.06-93.36%), 82.62% (95%CI: 81.65-83.61%), and 77.41% (95%CI: 76.29-78.55%) (P< 0.001). Inverse trends were observed for cumulative of cancer-specific mortality (CSM). Post-PSM analysis revealed that OS and CSM disparities between HPVAM and UEA patients were restricted to early-stage (IA1-IB2) and locally advanced (IB3-IVA) disease (P<0.05). Multivariable Cox regression analysis indicated that HPVAM patients exhibited poor responsiveness to chemoradiotherapy, whereas surgery significantly improved prognosis, even for locally advanced patients. Specifically, Kaplan-Meier and competing risks analysis for locally advanced HPVAM patients demonstrated that radical surgery provided superior prognosis compared to primary chemoradiotherapy. Concurrently, patients who underwent surgery following primary chemoradiotherapy showed significantly better OS and less CSM than those receiving chemoradiotherapy alone. Conclusion: HPVAM represents a distinct subtype with poor prognosis. Surgical intervention confers a significant survival benefit, even in locally advanced disease, while tumor responsiveness to chemoradiotherapy appears limited. Therefore, Surgery should be prioritized for locally advanced patients with HPVAM.