Cervical Cancer Screening (PDQ®): Screening - Health Professional Information [NCI] - Description of the Evidence
HPV DNA testing is generally not appropriate or clinically useful following cytology results of LSIL, which is more severe than ASCUS, and most of these women (84%–96%) are carcinogenic HPV DNA positive. One exception may be to clarify the risk for postmenopausal women with cytologic LSIL, which is an interpretation that can be falsely positive, presumably due to atrophic changes.
Testing for HPV DNA as a primary screening test has been FDA approved only in conjunction with cervical cytology and only in women aged 30 years and older. Women who are negative by cytology and HPV testing are at extremely low risk of CIN 3+ and therefore may be screened less often. A prospective cohort study of nearly 332,000 U.S. women aged 30 years and older undergoing HPV DNA and cervical cytology co-testing every 3 years found that the cumulative incidence of CIN 3+ in women negative for both tests at baseline was 0.047% at 3 years and 0.16% at 5 years. Screening more frequently than every 3 years would not improve sensitivity significantly but would increase costs and overtreatment.[51,52]
Numerous studies have demonstrated that, compared with cytology, HPV DNA testing is more sensitive for identifying women who have CIN 2+ (range of sensitivities 84%–97%).[32,53,54,55,56,57,58] In one randomized trial using both Pap and HPV testing in random order among women aged 30 to 69 years, sensitivity of HPV was 95% compared with 55% for Pap cytology. The combination of HPV and cytology had 100% sensitivity and a referral rate of 7.9%.
The lower specificity of HPV DNA testing compared with cytology is a consideration. Among women older than 30 years, cytology had a specificity of 97% compared with 94% for HPV testing. The specificity of HPV DNA testing would likely be even lower among women younger than 30 years, who have more transient HPV infection that is of little consequence. Thus, detecting such women would potentially increase the number of follow-up diagnostic workups. Potential approaches to minimize over-referral with HPV DNA testing and improve specificity include: (1) triage HPV-positive results with cytology  or another more specific molecular assay; and (2) trigger further workup only after two sequential positive HPV test results because it is the persistence of carcinogenic HPV that confers the greatest risk of CIN 2–3.[60,61]