Time to change perspectives on HPV in oropharyngeal cancer. A systematic review of HPV prevalence per oropharyngeal sub-site the last 3 years

Objectives: Human papillomavirus (HPV) as a risk factor in oropharyngeal squamous cell carcinoma (OPSCC) is well established. However, accumulating data imply that the OPSCC concept is too unspecific with regard to HPV prevalence and clinical importance. To further study the role of HPV in OPSCC by sub-site, a systematic review and meta-analysis was performed. Material and method: PubMed was searched and all studies reporting HPV data (p16/HPV DNA/RNA) in both lymphoepithelial associated (i.e. tonsillar and base of tongue cancer; TSCC and BOTSCC respectively) and non-lymphoepithelial (other OPSCC) OPSCC were included. Pooled odds ratios by HPV detection method were analysed using a random effects model. Results: In total, 58 unique patient cohorts were identified. Total HPV prevalence in TSCC/BOTSCC was 56%, 95% CI: 55-57% (59%, 95% CI: 58-60% for TSCC only) as compared to 19%, 95% CI: 17-20%, in other OPSCC. Significant association of HPV to TSCC/BOTSCC vs. other OPSCC was observed no matter HPV detection method used, but statistical homogeneity was only observed when studies using algorithm based HPV detection were pooled. Conclusion: HPV prevalence differs markedly between OPSCC sub-sites and while the role of HPV in TSCC/BOTSCC is strong, the role in other OPSCC is more uncertain and needs further evaluation.