Exploring the roles of HPV16 variants in head and neck squamous cell carcinoma: current challenges and opportunities

The incidence of squamous cell carcinomas of the head and neck (HNSCC) is consistently increasing, in association with human papillomavirus (HPV) infection, especially HPV16. HPV variants show heterogeneity in the pathogenicity of cervical cancer, but little has been established about their relevance on HNSCC. This review addresses the distribution of HPV16 variants in HNSCC and their potential contribution to clinical practice. A search was performed in PubMed using the keywords HNSCC HPV16 variants. Sixty articles were identified between 2000 and 2020 and 9 articles were selected for a systematic analysis. Clinical cohorts comprised 4 to 253 patients aged between 17 and 91 years with confirmed HPV16-positive HNSCC. Samples were collected from fresh biopsies of the tumour, oral rinse or formol fixed/paraffin embedded tissue, from the oral cavity, oropharynx, hypopharynx, larynx and Waldeyer's tonsillar ring. HPV16 variants were identified using Sanger sequencing techniques. Seven studies addressed the HPV16 E6 gene, one studied E6 and E7, another studied L1 and one focused on the long control region. European variants represent 25-95%, Asian-American 5-57% and African 2-4% of the total isolates, suggesting a marked predominance of European strains. No correlations could be drawn with patient prognosis, partly because many studies relied on small patient cohorts. Additional studies are needed, particularly those employing next generation sequencing techniques (NGS), which will allow faster and accurate analysis of large numbers of samples.