HPV Genotypes and Survival Outcomes in Invasive Cervical Cancer: A Retrospective Molecular Analysis of FFPE Clinical Samples in an Iranian Cohort

Background: High-risk human papillomavirus (HPV) genotypes differ in carcinogenic potential and may be associated with distinct clinical and survival outcomes in invasive cervical cancer. Methods: Tumor DNA was extracted from formalin-fixed paraffin-embedded (FFPE) cervical cancer samples (N = 120). HPV genotyping was then performed using a type-specific molecular assay (SENMURV HPV Genotyping Kit, Stem Cell Technology Co., Iran). The identified genotypes were subsequently grouped for survival analysis (HPV16 alone, HPV16 co-infection, HPV18-containing, and mixed infections with ≥3 types). Clinicopathologic and follow-up data were obtained from medical records, and overall survival was analyzed using Kaplan-Meier estimates and Cox proportional hazards models. Results: Single HPV16 infection was the predominant genotype pattern across the histologic subtypes, whereas HPV18-containing and multiple-genotype infections were less frequent and showed a non-significant trend toward poorer early survival. In multivariable Cox regression analysis, age remained the only independent predictor of overall survival (HR = 1.035; 95% CI: 1.005-1.065; p = 0.020), while histologic subtype and HPV genotype were not statistically significant. Overall, 33 deaths were observed during follow-up in the study cohort. Conclusion: Although no statistically significant associations were observed, HPV genotype-specific patterns suggested potential differences in survival, particularly for HPV18-containing infections. As exploratory, hypothesis-generating findings, these results highlight the need for larger, multicenter cohorts to clarify the independent prognostic role of HPV genotypes alongside established clinical factors.