Objective: The objective of the study was to evaluate the association between human papillomavirus (HPV) infection and clinical-pathological parameters in primary squamous cell carcinoma of the vagina and assess the value of HPV infection as a prognostic parameter.

Methods: In our retrospective study, we identified 37 consecutive patients with primary invasive squamous cell carcinoma of the vagina; 35 patients were eligible for further investigations. Human papillomavirus detection was assessed by in situ hybridization assays from paraffin-embedded tissue blocks. Human papillomavirus detection was correlated with clinical-pathological parameters by χ² and Fisher exact tests. Univariate log-rank tests and multivariate Cox regression models were used to evaluate the association between HPV infection and patient survival.

Results: Human papillomavirus DNA was detected in 18 (51.4%) of 35 cases. Human papillomavirus status did no influence clinical-pathological parameters, such as clinical stage (P = 0.9), grade (P = 0.9), and tumor size (P = 0.18). Prognosis did not significantly differ between HPV-positive and HPV-negative tumors in the entire cohort; however, patients with unfavorable tumor stage (International Federation of Gynecology and Obstetrics stage ≥III) and HPV positivity had improved disease-free (P = 0.004) and overall survival (P = 0.023).

Conclusions: Human papillomavirus infection was frequently detected in squamous cell carcinoma of the vagina, and its presence may serve as a prognostic indicator in advanced stages.