Presenter(s)
S. Pani1, C. D. S. Smith2, and A. N. Viswanathan3; 1Johns Hopkins University School of Medicine, Baltimore, MD, 2Johns Hopkins University, Baltimore, MD, 3Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine, Baltimore, MD
Purpose/Objective(s): Although prior studies have suggested that HPV may be associated with improved survival in squamous cell carcinoma (SCC) of the vulva, the independent prognostic value of HPV has not been fully established. We aimed to evaluate the association between HPV status and overall survival in patients with vulvar SCC using a large, nationally representative cohort.
Materials/Methods: Using the National Cancer Database (NCDB), we identified women diagnosed with histologically confirmed vulvar SCC between 2020 and 2022 with known HPV status and available survival data. HPV subtype is not reported by the NCDB. Overall survival (OS) was estimated using Kaplan–Meier methods. To account for baseline differences between HPV-positive and HPV-negative groups, inverse probability weighting (IPW) propensity scores were applied. Weighted Cox proportional hazards models were used to estimate hazard ratios (HRs) for OS according to HPV status, with analyses stratified by surgery alone vs radiotherapy (RT). Multivariable models were adjusted for age and stage to provide double-robust estimation. All statistical tests were two-sided, with p<0.05 considered statistically significant.
Results: Of the 573 patients diagnosed with vulvar SCC, 398 had available HPV status and were included, 272 (68%) of whom were HPV positive. The overall cohort had a median age of 65 (range 32 to 90), and patients were mostly early-stage (75% Stage 1, 7% Stage 2, 15% Stage 3, and 3% Stage 4). HPV-positive patients were more likely to be younger than 60 (37.1% vs 18.3%, p < 0.001), be on Medicaid or uninsured (17.6% vs 5.6%, p = 0.002), and be of Black race (7% vs 1.6%, p = 0.025). Twelve-month OS was higher in HPV-positive versus HPV-negative patients (94.6% vs 87.4%; log-rank p<0.001). IPW achieved good overall balance. In the surgery-only cohort (n = 291, HPV 69%), HPV-positive status was associated with significantly improved OS (IPW univariate HR 0.34, 95% CI 0.16-0.75, p = 0.007, adjusted HR 0.32, 95% CI 0.14–0.71, p = 0.005). The RT cohort (n = 107, HPV 66%) consisted of both postoperative RT patients (n = 59, HPV 64%) and definitive chemoradiation (n = 48, HPV 69%). In this cohort, HPV-positive status was also independently associated with improved OS (IPW univariate HR 0.42, 95% CI 0.19-0.91, p = 0.028, adjusted HR 0.37, 95% CI 0.18–0.79, p = 0.01).
Conclusion: HPV-positive vulvar SCC was associated with improved OS, remaining independently associated with reduced mortality in IPW Cox models across treatment strata. These findings support HPV status as a clinically relevant prognostic biomarker and underscore the importance of HPV assessment for vulvar cancer patients, while also highlighting the public health importance of HPV prevention. Prospective studies are needed to validate prognostic validity and refine risk stratification.