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. 2015 Apr 14;112(8):1349-57.
doi: 10.1038/bjc.2015.99. Epub 2015 Mar 17.

Detection of HPV-associated oropharyngeal tumours in a 16-year cohort: more than meets the eye

L J Melchers  1 , M F Mastik  2 , B Samaniego Cameron  2 , B A C van Dijk  3 , G H de Bock  4 , B F A M van der Laan  5 , B van der Vegt  2 , E J M Speel  6 , J L N Roodenburg  7 , M J H Witjes  7 , E Schuuring  2
Affiliations

Detection of HPV-associated oropharyngeal tumours in a 16-year cohort: more than meets the eye

L J Melchers et al. Br J Cancer. .

Abstract

Background: Accurate assessment of the prevalence of the human papilloma virus (HPV) in oropharyngeal tumours (OpSCC) is important because HPV-positive OpSCC are consistently associated with an improved overall survival. Recently, an algorithm has become available that reliably detects clinically relevant HPV in tumour tissue, however, no complete cohorts have been tested. The aim was to determine the prevalence of active high-risk HPV infection in a complete cohort of OpSCC collected over a 16-year period.

Methods: Using a triple algorithm of p16 immunohistochemistry, HPV-BRISH and HPV-PCR, we assessed the prevalence of active HPV infection in all OpSCC diagnosed in our hospital from 1997 to 2012 (n=193) and a random selection of 200 oral tumours (OSCC).

Results: Forty-seven OpSCC (24%) were HPVGP PCR-positive; 42 cases were HPV16+, 1 HPV18+, 3 HPV33+ and 1 HPV35+. Brightfield in situ hybridisation did not identify additional HPV-positive cases. Human papilloma virus-associated tumour proportion increased from 13% (1997-2004) to 30% (2005-2012). Human papilloma virus-positivity was an independent predictor for longer disease-specific survival (HR=0.22; 95%CI:0.10-0.47). Only one OSCC was HPV+.

Conclusions: In our cohort, the incidence of HPV-associated OpSCC is low but increasing rapidly. The strict detection algorithm, analysis of disease-specific survival and the complete cohort, including palliatively treated patients, may influence the reported prevalence and prognostic value of HPV in OpSCC.

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Figures

Figure 1
Figure 1
Case selection, HPV testing algorithm and results. After selection, cases were subsequently tested by p16 immunohistochemistry (p16), HPV-BRISH (only positive cases indicated), high-risk HPVGP5+/6+ PCR (HPV-GP), HPV-16 specific PCR (HPV-16) and sequencing.
Figure 2
Figure 2
Examples of various p16 intensities. (A) negative core; (B) weak intensity; (C) moderate intensity; (D) strong intensity. Only cases with any percentage of moderate or strong expression were considered p16-positive (core C and D).
Figure 3
Figure 3
HPV trends in OpSCC. Percentage of HPV+ OpSCC per 2-year period and the trend line (dashed). Absolute numbers of HPV-positive and HPV-negative cases per period are indicated below the graph.
Figure 4
Figure 4
Kaplan–Meier of disease-specific survival in OpSCC (n=193).
See this image and copyright information in PMC

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