Active HPV infection and its influence on survival in head and neck squamous-cell cancer

Abstract

Purpose: HPV is involved in the development of some head and neck squamous-cell carcinomas (HNSCC). It was suggested that only transcriptionally active virus can induce carcinogenesis, therefore, the aim of our study was to analyze the frequency of active HPV infection, virus type, and its prognostic role in HNSCC patients.

Methods: Status of active HPV infection was assessed for 155 HNSCC patients based on p16 expression and HPV DNA presence. Univariate and multivariate analyses with Cox proportional regression model were performed to select independent prognostic factors.

Results: Active HPV infection was detected in 20.65% of patients. We identified 16.0, 40.9 and 1.7% of HPV positive oral cavity, oropharyngeal, and laryngeal cancer cases, respectively. HPV16 was dominant (81.25%) followed by HPV35 (9.38%) and double infections with HPV16 and 35 (6.25%) or HPV35 and 18 (3.12%). Patients with active HPV infection demonstrated significantly higher survival than HPV negative ones (OS 80.89% vs. 37.08%, p = 0.000; DFS 93.0% vs. 53.35%, p = 0.000, respectively). Longer OS and DFS were maintained for infected patients when oropharyngeal and non-oropharyngeal cases were analyzed separately. Interestingly, all patients infected with other than HPV16 types survived 5 years without cancer progression. In the analyzed group of 155 patients the strongest independent favourable prognostic factor for both OS and DFS was HPV presence.

Conclusions: High prevalence of HPV-driven HNSCC (mostly within oropharynx) was detected, with HPV16 type the most frequent, followed by HPV35 and HPV18. The presence of active HPV infection improved survival of both oropharyngeal and non-oropharyngeal cancer patients and should be taken into account in treatment planning.

Keywords: Active infection; HNSCC; HPV; Nested PCR; Survival; p16 overexpression.

Fig. 1

Representative images of p16 negative (a) and positive (b) signal in HNSCC tissue based on immunohistochemical staining using CINtec p16^INK4a Histology Kit (Roche, Germany)

Fig. 2

HPV prevalence in HNSCC patients from South-Central Poland. The results of nested PCR, genotyping experiments and immunohistochemical staining of p16 are presented. After combining the data of all 3 methods tumours with active HPV infection (i.e. nested PCR + /qPCR + /p16 +) were identified. Numbers of HPV positive per all analyzed cases are presented in brackets