The overexpression of p16 is not a surrogate marker for high-risk human papilloma virus genotypes and predicts clinical outcomes for vulvar cancer

Abstract

Background

We aimed to evaluate the correlation between p16 ^ink4a-overexpression and high risk (hr)HPV-DNA in vulvar squamous cell carcinoma (vSCC) tumors as well as the impact of both biomarkers on the prognosis of vSCC patients.

Methods

PCR-detection of (hr)HPV-DNA and immunohistochemical staining for p16 ^ink4a were conducted in 85 vSCC tumors. Survival analyses included the Kaplan–Meier method, log-rank test and Cox proportional hazards model.

Results

p16 ^ink4a-overexpression and (hr)HPV-DNA were detected in 35 and 37 of the 85 tumors, respectively. Among the 35 p16 ^ink4a-positive tumors, 10 lacked (hr)HPV-DNA (29 %). Among the 50 p16 ^ink4a-negative tumors, (hr)HPV-DNA was detected in 12 cases (24 %). The median follow-up was 89.20 months (range 1.7–189.5 months). P16 ^ink4a-overexpression, but not (hr)HPV-DNA positivity of the primary tumor, was correlated with prolonged overall survival (OS) ( p = 0.009). P16 ^ink4a-overexpression predicted a better response to radiotherapy ( p < 0.001). Univariate analysis has demonstrated that age ( p = 0.025), tumor grade ( p = 0.001), lymph node metastasis ( p < 0.001), FIGO stage ( p < 0.001), p16 ^ink4a-overexpression ( p = 0.022), and adjuvant RTX ( p < 0.001) were prognostic factors for OS. Multivariate analysis has demonstrated that lymph node metastasis (HR 1–2.74, 95 % CI 1.50–5.02, p = 0.019), tumor grade (HR 1–2.80, 95 % CI 1.33–5.90, p = 0.007) and p16 ^ink4a-overexpression (HR 1–2.11, 95 % CI 1.13–3.95, p = 0.001) are independent prognostic factors.

Conclusion

The discovered overlap suggests the use of p16 ^ink4a in combination with HPV-DNA detection as an ancillary test for future research and clinical studies in vSCC. The prognostic and predictive value of p16 ^ink4a-overexpression should be tested in larger cohort studies.

Electronic supplementary material

The online version of this article (doi:10.1186/s12885-016-2503-y) contains supplementary material, which is available to authorized users.