Prognostic importance of human papillomavirus (HPV) and p16 positivity in squamous cell carcinoma of the vulva treated with radiotherapy

Larissa J. Lee, Brooke Howitt, Paul Catalano, Cynthia Tanaka, Rita Murphy, Nicole Cimbak, Rebecca DeMaria, Paula Bu, Christopher Crum, Neil Horowitz, Ursula Matulonis, Akila N. Viswanathan

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Objective HPV status is an important prognostic factor for patients with oropharyngeal, anal and cervical cancers treated with radiotherapy. This study evaluates the association between HPV and p16 status and outcome in a radiation-treated cohort with vulvar squamous cell carcinoma (SCC). Methods Patients with vulvar SCC who received radiotherapy with or without surgical resection between 1985 and 2011 were identified retrospectively. Immunostaining for p16 and multiplex PCR for HPV genotyping were performed using archival tumor tissue from 57 patients. Actuarial estimates of PFS, OS and in-field recurrence were calculated using the Kaplan-Meier method. Cox proportional hazards models were used for multivariable analysis. Median follow-up was 58 months among the 57 patients with an available tumor specimen. Results HPV prevalence was implied in 37% by (diffuse linear) p16 immunostaining and confirmed in 27% by HPV PCR with good agreement (κ = 0.7). HPV-16 was identified in 80% of HPV-positive tumors. Women with p16-positive tumors had significantly higher 5-year PFS (65% vs. 16%, p < 0.01) and OS (65% vs. 22%, p = 0.01) rates, as well as lower in-field relapse rates (19% vs. 75%, p < 0.01) compared to those with p16-negative disease. On multivariable analysis adjusted for age and stage, p16 positivity was significantly associated with better PFS (HR 0.4, 95% CI 0.2–0.9) and lower rates of in-field relapse (HR 0.2, 95% CI 0.06–0.6). Results were similar when analyzed by HPV DNA status. Conclusion In this study, the presence of HPV or its surrogate of p16 immunostaining was an independent prognostic factor for in-field relapse and survival in women with vulvar SCC treated with radiotherapy. This finding warrants validation in larger cohorts or the prospective setting.

Original languageEnglish (US)
Pages (from-to)293-298
Number of pages6
JournalGynecologic oncology
Issue number2
StatePublished - Aug 1 2016
Externally publishedYes


  • Human papillomavirus
  • Radiotherapy
  • Vulvar cancer
  • p16

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology


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