Prevalence of high-risk human papilloma virus genotypes and associated risk of cervical precancerous lesions in a large U.S. screening population: Data from the ATHENA trial

•HPV 16 was the most common genotype in all populations and conferred the highest risk for high grade disease.•We found that 50% of the adenocarcinoma in situ and 50% of the invasive cancer cases were attributable to HPV18 infection.•We confirmed the utility of 16/18 genotyping in cervical cancer screening strategies, while pooled detection of non-16/18 genotypes is sufficient.

ObjectiveWe assessed the age-related prevalence of high risk human papillomavirus (HR-HPV) genotypes and the genotype-associated risk for high-grade cervical intraepithelial neoplasia (CIN) in a large U.S. screening population.MethodsA total of 40,901 women aged ≥ 25 years were screened with liquid-based cytology and HPV testing in the ATHENA (Addressing the Need for Advanced HPV Diagnostics) trial. Genotyping was performed using the LINEAR ARRAY HPV Genotyping Test.ResultsHPV16 was the most prevalent genotype in all age groups, ranging from 3.5% to 0.8% in women aged 25-29 and ≥ 50 years, respectively. The next most prevalent genotypes were HPV52, HPV31 and HPV18. In the overall population, HPV16 conferred the greatest absolute risk of ≥ CIN3 both in women aged 25-29 and ≥ 30 years (14.2% and 15.1%, respectively) followed by HPV31 (8.0% and 7.9%), HPV52 (6.7% and 4.4%) and HPV18 (2.7% and 9.0%). Similar trends were seen in women with negative cytology. The percent positivity increased markedly with disease progression for HPV16 and HPV18 which were responsible for 45.6% and 8.4% of ≥ CIN3, respectively. Of note, HPV 18 was responsible for 50% of adenocarcinoma in situ (AIS) and 50% of invasive cancer cases.ConclusionsHPV16 played a major role in the development of ≥ CIN3 irrespective of age, supporting the identification of HPV16 in primary screening for all women. Identification of HPV18 is also warranted, given its significant contribution to AIS and cancer. Identification of non-16/18 genotypes as a pool should provide sufficient information for screening.