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Authors: Schiffman M,  Burk RD,  Boyle S,  Raine-Bennett T,  Katki HA,  Gage JC,  Wentzensen N,  Kornegay JR,  Aldrich C,  Tam T,  Erlich H,  Apple R,  Befano B,  Castle PE
Journal: J Clin Microbiol
Date: 2014 Oct 22
Branches: BB, CGB, HREB
PubMed ID: 25339396
PMC ID: not available
Abstract: Objectives: Effective management of women with HPV-positive, cytology-negative results is critical to the introduction of HPV testing into cervical screening. HPV typing has been recommended for colposcopy triage, but it is not clear which combinations of high-risk HPV types provide clinically useful information. Methods: The study included 18,810 HC2-positive, cytology-negative women aged 30 and older from Kaiser Permanente Northern California. Median follow-up was 475 days (IQR 0-1077, maximum 2217). Baseline specimens from 482 cases of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) and 3,517 random HC2-positive non-cases were genotyped using 2 PCR-based methods. Using the case-control sampling fractions, 3-year cumulative risks of CIN3+ for each individual high-risk HPV type were calculated. Results: The 3-year cumulative risk of CIN3+ among all HC2-positive, cytology-negative women was 4.7%. Knowing HPV16 status conferred the greatest type-specific risk stratification; HC2-positive/HPV16-positive women had a 10.6% risk of CIN3+ while HC-2 positive/HPV16-negative women had a much lower risk of 2.4%. The next most informative HPV types and their risks in HPV-positive women were: HPV33 (5.9%) and HPV18 (5.9%). With regard to etiologic fraction, 20 of 71 cases of cervical AIS and adenocarcinoma in the cohort were positive for HPV18. Conclusion: HPV16 genotyping provides risk stratification useful to guide management; the risk among HPV16-positive women clearly exceeds the US consensus "risk threshold" for immediate colposcopy referral. HPV18 is of particular interest because of its association with difficult-to-detect glandular lesions. There is less clear clinical value to distinguishing the other high-risk HPV types.