The impact of p16ink4a positivity in invasive vulvar cancer on disease-free and disease-specific survival, a retrospective study

Abstract

Purpose To evaluate HPV and p16 ink4a status as prognostic factors in patients with invasive vulvar cancer. Methods Retrospective analysis of disease-free (DFS) and disease-specific survival (DSS) of patients with invasive vulvar cancer at a single tertiary care center. Histology, HPV and p16 ink4a status were evaluated in the context of a global multicenter trial. Logistic regression models were performed to identify the impact of p16 ink4a positivity. Results 135 patients were included in the analysis. 32 (23.7%) showed a p16 ink4a expression of over 25%. Disease-free and disease-specific survival was longer in p16 ink4a positive patients (23 vs. 10 months, p = 0.004, respectively, 29 vs. 21 months, p = 0.016). In multivariate analysis, p16 ink4a positivity was an independent parameter for DFS (p = 0.025, HR: 2.120 (1.100-4.085)), but not for DSS (p = 0.926, HR: 1.029 (0.558-1.901), in contrast to age and tumor stage. Conclusions Age and tumor stage negatively affect survival. However, disease-free survival is significantly longer in patients with p16 ink4a positive invasive vulvar cancer.

Time trends in prevalence of p16 positivity and combined HPV/p16 positivity in a large cohort of Danish vulvar cancer patients

“…Furthermore, the nearly three decades long study period gave us the opportunity to investigate changes in prevalence over time, adding new knowledge of the patterns of HPV and p16 positivity over time. The fact that we tested for both hrHPV and p16 overexpression is also an important strength, because detection of hrHPV in a tumor sample without simultaneous detection of p16 positivity could indicate the presence of a transient bystander HPV infection 36 . Therefore, the proportion of HPV‐driven tumors could be overestimated by only testing for HPV DNA.…”

“…The fact that we tested for both hrHPV and p16 overexpression is also an important strength, because detection of hrHPV in a tumor sample without simultaneous detection of p16 positivity could indicate the presence of a transient bystander HPV infection. 36 Therefore, the proportion of HPV-driven tumors could be overestimated by only testing for HPV DNA. Furthermore, we applied centralized and standardized methods for HPV testing and p16 staining, which reduced the risk of inconsistencies in the data and ensured high validity of the results.…”

Cold Atmospheric Pressure Plasma (CAP) as a New Tool for the Management of Vulva Cancer and Vulvar Premalignant Lesions in Gynaecological Oncology

“…The dVIN is the precursor lesion of keratinising SCC, which is the most common subtype of invasive SCC, accounting for 63-86% of all cases of VSCC [118]. The second pathway is caused by a persistent human papillomavirus (HPV) infection (mostly HPV type 16, 33, and 18), with HSIL/uVIN as the associated precursor of warty and basaloid invasive SCC [116], but with better prognosis, longer disease-free survival [123] and better response to radiotherapy [124] than HPV-negative ones, and this is the same for the invasive form of vulvar cancer [103].…”