HPV16 Intratypic Variants in Head and Neck Cancers: A North American Perspective

• Published in: Viruses Vol. 15; no. 12; p. 2411
• Main Authors: Gameiro, Steven F, Salnikov, Mikhail Y, Zeng, Peter Y F, Barrett, John W, Nichols, Anthony C, Mymryk, Joe S
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.12.2023
• Subjects: Amino acids; Asian Americans; Cancer therapies; Causes of; Cell cycle; Cervical cancer; Clonal selection; Complications and side effects; Ethanol; Female; Genetic aspects; Genetic diversity; Genetic polymorphisms; Genomes; Head & neck cancer; Head and neck cancer; Head and Neck Neoplasms - genetics; head and neck squamous cell carcinoma; Human papillomavirus; Human papillomavirus 16 - genetics; Humans; Immune response; Infections; intratypic variants; Lymphocytes B; Medical prognosis; North America; Oncogene Proteins, Viral - genetics; Ontario; Papillomavirus Infections; Papillomaviruses; Patients; Phylogenetics; Polymorphism, Single Nucleotide; Positive selection; Single-nucleotide polymorphism; Squamous cell carcinoma; Statistical analysis; TCGA; Uterine Cervical Neoplasms; Virus research; North America; Ontario; Canada; Germany; E6; intratypic variants; TCGA; human papillomavirus; head and neck squamous cell carcinoma
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v15122411

Human papillomavirus (HPV) is the major causative agent for cervical and many head and neck cancers (HNCs). HPVs randomly acquire single nucleotide polymorphisms (SNPs) that may become established via positive selection. Within an HPV type, viral isolates differing by <2% in the L1 region are termed "variants" and classified based on combinations of SNPs. Studies in cervical cancer demonstrate clear differences between HPV16 intratypic variants in terms of persistence of infection, tumor histology, cancer risk, and death. Much less is known about the frequency of HPV16 variants in HNC, and their effects on clinical outcomes. We combined HPV16 positive (HPV16 ) HNC samples from a local Southwestern Ontario, Canada cohort with those from the Cancer Genome Atlas to create a larger North American cohort of 149 cases with clinical data and determined the distribution of intratypic variants and their impact on clinical outcomes. Most isolates were lineage A, sublineage A1, or A2, with roughly half exhibiting the T350G polymorphism in . Univariable analysis identified significant differences between 350T and 350G intratypic variants in clinical T, N, and O staging, as well as disease-free survival. Multivariable analysis failed to identify any clinical factor as a statistically significant covariate for disease-free survival differences between 350T and 350G. Significant differences in several measures of B-cell mediated immune response were also observed between 350T and 350G intratypic variants. We suggest that HPV genetic variation may be associated with HNC clinical characteristics and may have prognostic value.