There are few large case series describing the HPV genotypes found in women diagnosed with rigorously reviewed cervical intraepithelial neoplasia grade 3 (CIN3), cervical precancer.
The Atypical Squamous Cells of Undetermined Significance (ASCUS) and Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study (ALTS) was a clinical trial to evaluate the best management strategies for women with equivocal (ASCUS) or mildly abnormal (LSIL) Pap tests. During enrollment and the two-year follow-up, 608 women had a histopathologic diagnosis of CIN3 and PCR-based HPV genotyping results. The genotyping results were ranked hierarchically according to cancer risk: HPV16 > other carcinogenic HPV > non-carcinogenic HPV > PCR negative.
Among the 608 women diagnosed with CIN3, 601 (98.8%) cases were positive for any HPV genotype and 95.4% for any carcinogenic HPV. HPV16 (59.9%), HPV31 (18.1%), HPV52 (14.8%), HPV51 (14.0%), and HPV18 (13.2%) were the 5 most common HPV genotypes detected. Younger age, consensus histologic confirmation, smoking, and multi-parity increased the likelihood of testing HPV 16 positive. Specifically, HPV16-positive CIN3 occurred at a younger age than CIN3 positive for other carcinogenic HPV genotypes (median of 23.5 years versus 25 years, respectively, p = 0.0003, Kruskal-Wallis).
HPV16-positive CIN3 was more commonly diagnosed in younger women (vs. older women), with consensus diagnosis (vs. some disagreement between reviewers), and in smokers (vs. non-smokers), and less commonly diagnosed in multi-parous women.
In populations vaccinated against HPV16 (and HPV18), the median age of CIN3 in women with ASC-US and LSIL cytology should shift to older ages, possibly permitting later age at first screening.