Human papillomavirus prevalence, genotype distribution, and prognostic factors of vaginal cancer

We aimed to investigate human papillomavirus (HPV) prevalence and genotype distribution and prognostic factors in vaginal cancer (VC). VC patients who received treatment between 1989 and 2020 were retrospectively reviewed. L1 general polymerase chain reaction (PCR) followed by HPV Blot (King Car, I‐Lan, Taiwan) and E6 type‐specific‐PCR were performed for genotyping firstly. P16 and p53 immunohistochemistry staining was performed. Univariate and multivariate analyses identified predictors of clinical outcomes.79 VC patients were eligible for analysis. 73 patients (92.4%) were squamous cell carcinoma (SCC) and 6 (7.6%) as non‐SCC. The median follow‐up time was 134.3 months (range 0.9–273.4). Among nine initially HPV‐negative cases, seven were identified as being positive through HPV16/18/45/52/58 whole‐genome amplification followed by Sanger sequencing (WGASS). HPV DNA sequences were detected in 98.6% of SCC and 83.3% of non‐SCC, respectively, with HPV16 (49.4%), HPV52 (15.2%) and HPV58 (8.9%) being predominant. Patients with paraaortic lymph node (LN) metastasis had a 5‐year cancer‐specific survival (CSS) rate of 0%. Multivariate analysis revealed that only p16 and stage were significantly correlated with prognosis. Variables with strong correlations (p16‐ and HPV‐positivity, LN metastasis and stage), were included in models 2–5 alternatively. Stage III/IV (hazard ratio [HR] = 3.64–4.56) and LN metastasis (HR = 2.81–3.44) were significant negative predictors of CSS, whereas p16‐positivity (HR = 0.29–0.32) and HPV‐positivity (HR = 0.14) were related to better prognosis. In conclusion, 97.5% of VCs were HPV‐positive with WGASS. Stage III/IV and LN metastasis were significant negative predictors, whereas p16‐ and HPV‐positivity were significantly associated with better prognosis. What's new? Human papillomavirus (HPV) infection is a leading risk factor for squamous cell carcinoma (SCC) vaginal cancer (VC). Associations between HPV and prognosis of the SCC subtype of VC, however, remain unclear. In this study, HPV prevalence and genotype distribution were investigated in the context of VC prognosis. HPV DNA sequences were detected in 98.6% of SCC and 83.3% of non‐SCC cases. HPV types 16, 52, and 58 were the most commonly detected sequences. Advanced stage disease and lymph node metastasis were associated with poor prognosis, while prognosis was better among those with p16‐ or HPV‐positivity.