High-Risk HPV Types Affecting People Of African Ancestry Not Covered By 9-Valent Vaccine

The current 9-valent human papillomavirus (HPV) vaccine does not include high-risk HPV (hrHPV) types that are more prevalent in individuals of African ancestry, a pan-hrHPV analysis of squamous-cell carcinomas (SCCs) shows.

The authors urge inclusion in the vaccine of HPV types 35 and 59, which accounted for more than 10% of SCCs in those of African ancestry, but only 2% of SCCs in individuals of other ancestries.

"The current 9-valent vaccine is highly effective, and our findings should not discourage its use," Dr. Erik Williams of the University of California, San Francisco, told Reuters Health by email. "Nevertheless, our data argue for the addition of HPV types 35 and 59. Future studies and vaccine decisions should involve consideration of ancestrally diverse populations."

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"In early-stage samples - i.e., routine non-cancerous cervical swabs and resectable cervical precancer - the distribution of high-risk HPV types was already known to differ by racial/ethnic group, with African-American women showing increased rates of HPV-35 infection compared with other ethnicities," he said.

"Our study shows that these previous findings also apply to advanced, invasive SCCs," he added. "We found that HPV-35 infection is increased in individuals of African ancestry in advanced-stage cervical disease, as well as in other HPV-related invasive carcinomas."

"Genomic ancestry is distinctly different than self-reported race," he noted. "In our study, patient ancestry was determined by classifying specific single-nucleotide variations by genomic profiling based on known variations among populations in the 1000 Genomes Project."

As reported inJAMA Network Open, researchers analyzed Foundation Medicine's archive of more than 290,000 tumor samples from facilities across North America. Genomic profiling for detection of targetable HPV genetic alterations showed hrHPV genomic sequences in 3,793 cervical, anogenital, and head and neck SCCs.

Five hrHPV types were identified, each with 10 or more SCC cases in individuals of African ancestry: HPV-16 (193 cases), HPV-18 (56), HPV-35 (17), HPV-45 (27), and HPV-59 (16).

Compared with non-African populations, individuals of African ancestry showed significant, several-fold enrichments for HPV types 35 (5.3% vs. 1.6%), 45 (8.4% vs. 3.4%), and 59 (5.0% vs. 0.5%); after stratification by site, enrichments were significant for cervical (HPV-35, 5.2% vs. 1.3%; HPV-59, 9.0% vs. 0.9%) and anal (HPV-45, 7.0% vs. 1.0%) cancers.

The two hrHPV types not included in the current vaccine - i.e., HPV-35 and HPV-59 - accounted for 10.3% of all hrHPV-related SCCs in persons of African ancestry, but only 2.1% of cases in individuals of other ancestries, nearly five-fold difference.

Notably, the authors state, "Tumor mutational burden and genomic alterations showed essentially no significant differences based on patient ancestry, suggesting similar tumorigenic mechanisms."

Dr. Nicolas Schlecht, a professor of oncology in the Department of Cancer Prevention and Control at Roswell Park Comprehensive Cancer Center in Rochester, New York, told Reuters Health by email, "It is important to emphasize that while the prevalence of non-vaccine hrHPV types was higher among individuals of African ancestry compared to those of non-African ancestry, the absolute risks, as reflected by the fraction of cancers attributed to non-vaccine hrHPV types, are much lower than what we see with the vaccine types."

Overall, he said, "The study findings support HPV vaccination, which is highly effective at preventing the vast majority of HPV-associated cancers, including among communities of African ancestry."

"Screening by cytology and HPV testing remain important even after vaccination," he added.

The study was funded by and conducted at Foundation Medicine Inc., a wholly owned subsidiary of Roche Holdings Inc. and Roche Finance Ltd. Several coauthors are employees of or consultants to the company.

—Marilynn Larkin

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