High-risk human papillomavirus in oral cavity squamous cell carcinoma

ABSTRACT Purpose The prevalence of human papillomavirus (HPV) in oral cavity squamous cell carcinoma (OSCC) varies significantly based on assay sensitivity and patient geography. Accurate detection is essential to understand the role of HPV in disease prognosis and management of patients with OSCC. Methods We generated and integrated data from multiple analytes (HPV DNA, HPV RNA, and p16), assays (immunohistochemistry, PCR, qPCR and digital PCR) and molecular changes (somatic mutations and DNA methylation) from 153 OSCC patients to correlate p16 expression, HPV DNA, and HPV RNA with HPV incidence and patient survival. Results High prevalence (33-58%) of HPV16/18 DNA did not correlate with the presence of transcriptionally active viral genomes (15%) in tumors. Eighteen percent of the tumors were p16 positive. and only 6% were both HPV DNA and RNA positive. Most tumors with relatively high-copy HPV DNA, and/or HPV RNA, but not with HPV DNA alone (irrespective of copy number), were wild-type for TP53 and CASP8 genes. In our study, p16 protein, HPV DNA and HPV RNA, either alone or in combinations, did not correlate with patient survival. Nine HPV-associated genes stratified the virus +ve from the –ve tumor group with high confidence (p<0.008) when HPV DNA copy number and/or HPV RNA were considered to define HPV positivity and not HPV DNA alone irrespective of their copy number ( p < 0.2). Conclusions In OSCC, the presence of both HPV RNA and p16 are rare. HPV DNA alone is not an accurate measure of HPV positivity and therefore not informative. Moreover, HPV DNA, RNA or p16 don’t correlate with outcome.