Prognostic significance of human papillomavirus DNA in vulvar carcinoma

Objective: To determine the histopathologic, epidemiologic, and prognostic significance of human papillomavirus (HPV) DNA in primary invasive vulvar cancer. Methods: From December 1981 through October 1992, primary tumor tissue from 55 newly diagnosed vulvar cancers was evaluated for the presence of HPV DNA. The DNA was extracted from tumor tissue and subjected to the polymerase chain reaction (PCR) using highly conserved consensus Ll primers that detect 25 different HPV genotypes and primers specific for HPV type 6/E6, type 16/E7, and type 18/E6 gene sequences. All PCR products were hybridized to type-specific radiolabeled probes. The association between the presence of HPV DNA and histologic, epidemiologic, and clinical characteristics was analyzed. Results: Thirty-three (60%) tumors contained HPV DNA. Patients younger than 70 years of age or who smoked were more likely to have HPV-positive vulvar cancers. Twenty-one (95%) of 22 tumors classified as basaloid, warty, or verrucous contained HPV DNA, whereas 12 (39%) of 31 typical squamous tumors contained HPV (P < .001). Two adenocarcinomas were negative for HPV. Tumors with or without HPV DNA did not differ with respect to International Federation of Obstetricians and Gynecologists stage (size and nodal status), tumor grade, or therapy. Using life-table analysis, the absence of HPV DNA and the presence of regional nodal metastasis were predictive of recurrence and death from vulvar cancer. When controlling for lesion size, age, tumor grade, and nodal metastasis using the Cox proportional hazards model, only HPV status remained an independent prognostic factor. Conclusion: Human papillomavirus DNA is more common in vulvar cancers of young women who smoke than in older nonsmokers. Patients with HPV-negative tumors are at an increased risk of recurrence and death from vulvar cancer.