Prognostic significance of lymph node variables and human papillomavirus DNA in invasive vulvar carcinoma

Abstract

Objective. The present study investigates the influence of lymph node pathological features and HPV DNA status on the prognosis of vulvar invasive tumors. Methods. This study includes 184 consecutive cases of primary invasive squamous cell carcinoma of the vulva treated by radical surgery from 1975 to 1992, in São Paulo, Brazil. Clinical follow-up data was collected from patient files and hematoxilin–eosin sections were reviewed. HPV detection and typing was done by polymerase chain reaction (PCR), using specific and generic primers, followed by dot blot hybridization (DBH) with type-specific oligonucleotide probes for 19 HPV types. Age-adjusted Kaplan–Meier survival curves and Cox proportional hazards models were used to analyze the cancer risk associations for all DNA and pathology-related variables. Results. Among 161 cases tested by PCR, 38 (23.6%) were positive for high-risk HPV types. Regional lymph nodes of 43 cases, including all those of HPV-positive tumors and a sample of the ones removed from patients with HPV negative tumors, were evaluated by the same method. HPV DNA was found in the lymph nodes of 10 cases. In every case, at least one lymph node was metastatic and the HPV detected in the lymph nodes were of the same type as those found in the primary tumor in all cases. Multivariate analysis including age, race, pattern of invasion, tumor thickness, inflammatory reaction, surgical margins, number of node metastases, presence of extracapsular growth, depth of invasion, and presence of high-risk HPV DNA was performed. Following automated selections of this model, node variables important for prognosis that remained were number of node metastases and presence of extracapsular growth. Conclusions. Patients with four or more node metastases associated with extracapsular spread were 5.6 (95%CI: 2.3–13.1) times more likely to die from cancer and 10.0 (95%CI: 4.0–24.9) times more likely to have a recurrence than patients without metastases. The HPV status in the tumor was not important as a prognostic factor.