Differences in the viral genome between HPV-positive cervical and oropharyngeal cancer

Abstract

Human papillomavirus (HPV)-driven oropharyngeal cancer incidence in the United States has steadily increased in the past decades and has now become the most frequently diagnosed HPV-associated cancer type, surpassing cervical cancer. Variations in the HPV genome correlate with tumorigenic risk, and the distribution of genetic variants is extensively studied in cervical cancer, but very little is known about new mutations or the distribution of HPV types and variants in oropharyngeal cancer. Here we present an archival tissue cohort study that compares genomic characteristics of HPV associated with cervical versus oropharyngeal tumors using DNA sequence analysis. We found HPV16 to be more prevalent in oropharyngeal samples than in cervical samples (91.2% versus 52.9%), while HPV18 (1.5% versus 18.2%) and HPV45 (0.7% versus 9.9%) were much less prevalent. Differences between cervix and oropharynx in HPV16 variants distribution were more subtle, but the combined European + Asian (EUR+AS) variant group was more prevalent (90.2% versus 71.4%), while the American Asian 1 + American Asian 2 (AA1+AA2) variant group was much less prevalent (4.4% versus 22.5%) in oropharyngeal cancers. HPV prevalence in oropharyngeal cancers showed an increasing trend from 60% in 2003 to 80% in 2016. We also identified over nine times more nonsynonymous mutations in the HPV E6 gene amplified from oropharyngeal samples, but for E7 the difference in mutation rates between the two anatomical locations was not significant. Overall, we showed that HPV genome in oropharyngeal cancer presents important differences when compared to cervical cancer and this may explain the distinct pathomechanisms and susceptibility to treatment of HPV-associated oropharyngeal cancer.

Human papillomavirus infection among head and neck squamous cell carcinomas in southern China

“…This discrepancy probably reflects socio-economic differences between the catchment areas of the two hospitals. In a recent study, HPV type 35 was found as the 2 nd most dominant HPV type in OPC tumours in USA [29], which is different from ours, probably geographic, ethnicity differences that contribute to the discrepancy.…”

Whole-Genome Analysis of Human Papillomavirus Type 16 Prevalent in Japanese Women with or without Cervical Lesions

“…The E7 L28F substitution, which is characteristic for A5 variants, was previously identified in Japanese sex workers [42], and was also reported from Thailand [33] and northeast China [43]. A more recent study also described the same E7 substitution in one oropharyngeal cancer case in the United States [44]. To date, however, the complete genome sequence of a virus harboring the E7 L28F substitution has only been reported for one isolate in Thailand [33].…”

Epidemiology and Burden of Human Papillomavirus and Related Diseases, Molecular Pathogenesis, and Vaccine Evaluation

“…Cervical cancer (CC), the third most prevalent cancer in women ( 7 ), is an HPV-related disease for which the burden is the most blatant, as it leads to high mortality in women after breast cancer ( 8 ). Overall, the epidemiologic distribution of HPV infection and HPV-associated burden vary significantly across the world, and the morbi-mortality–associated factors include geographic, socioeconomic, cultural, and genetic factors related to viral genome variability as well as intrinsic individual factors such as age, gender, anatomic site, and health state ( 9 ). The three types of currently approved HPV vaccines, including bivalent, tetravalent, and 9-valent vaccines, are effective in reducing HPV infection and HPV-related disease incidence, as reported in several world regions.…”