Does HPV status influence survival after vulvar cancer?

Abstract

High-risk human papillomavirus (HPV) infection is essential in the carcinogenesis of a substantial part of anogenital and oropharyngeal cancers and has additionally been shown to be a possible predictive marker for survival, especially in oropharyngeal cancer. Studies examining the influence of HPV status on survival after vulvar cancer have been conflicting and limited by small study populations. Therefore, the aim of this review and meta-analysis was to examine whether HPV status influences survival after vulvar cancer, which, to our knowledge, has not been done before. We conducted a systematic search of PubMed, Cochrane Library and Embase to identify studies examining survival after histologically verified and HPV tested vulvar cancer. A total of 18 studies were eligible for inclusion. Study-specific and pooled HRs of the 5-year OS and DFS were calculated using a fixed effects model. The I statistic was used to describe heterogeneity. The studies included a total of 1,638 women with HPV tested vulvar cancers of which 541 and 1,097 were HPV-positive and HPV-negative, respectively. Fifteen studies included only squamous cell carcinomas. We found a pooled HR of 0.61 (95% CI: 0.48-0.77) and 0.75 (95% CI: 0.57-1.00) for 5-year OS and DFS, respectively. Across study heterogeneity was moderate to high (OS: I = 51%; DFS: I = 73%). In conclusion, women with HPV-positive vulvar cancers have a superior survival compared to women with HPV-negative, which could be of great clinical interest and provides insight into the differences in the natural history of HPV-positive and negative vulvar cancers.

Prognostic Significance of HPV and p16 Status in Men Diagnosed with Penile Cancer: A Systematic Review and Meta-analysis

“…Our results support the hypothesis that HPV-positive and HPVnegative penile cancers differ in relation to survival outcome, which has also been found in other HPV-associated cancers including vulvar and oropharyngeal SCC (12,15). However, the explanation for the prognostic significance of HPV status is still unclear.…”

“…HPV status has been identified as a possible prognostic marker in some HPV-associated cancers; specifically, HPV-positive oropharyngeal squamous cell carcinomas (SCC) have a more favorable clinical outcome compared with HPV-negative (8)(9)(10)(11). In addition, in a recent meta-analysis we found that women with HPV-positive vulvar cancer have a superior overall survival (OS) and disease-free survival (DFS) compared with women with HPV-negative vulvar cancer (12). Penile cancer displays many similarities to vulvar cancer including histology, risk factors, and natural history (13); however, studies examining the association between HPV status and survival in penile cancer are often inconclusive because of small study populations.…”

Inflammation as a Driver of Vulvar Squamous Cell Carcinoma Progression.

“…A similar approach was previously con rmed by Sandberg et al [22] while detecting protein alterations related to HPV infection in a set of VSCC tumors. An increasing evidence suggests that HPVharboring VSCC tumors are less aggressive, though some ambiguities remain regarding the prognostic value of HPV status because of the different HPV testing methods applied, and the low numbers of cases examined in some studies [23][24][25]. In our study, we analyzed a cohort of early-stage VSCC patients with a long-term follow-up after surgery, which enabled strati cation of cases according to treatment outcomes.…”

Vaginal Dysplasia and HIV: An African American and Caribbean American Cohort Study

“…It was not possible to fully assess HPV positivity, nor the true rate of VaIN recurrence in this cohort, but two interesting findings in the literature regarding HPV and VaIN recurrence are worth noting here. First, while HPV positivity is a known precursor to anogenital dysplasia and cancer, a recent meta-analysis demonstrated that HPV positivity in vulvar cancer and other cancers, head and neck cancer, for example, predicted significantly longer survival [25]. Second, studies that reported on factors associated with VaIN and its recurrence posttreatment suggested that among the general, non-HIV population the correlation may be due to closer monitoring that occurs after hysterectomy [15].…”