Clinical Question: Should cervical cytology results showing atypical squamous cells of undetermined significance (ASC-US) be followed by human papillomavirus (HPV) triage as a diagnostic testing strategy?

Setting: Outpatient (any)

Study Design: Randomized controlled trial (nonblinded)

Synopsis: Annually, an estimated 3 million women in the United States have Papanicolaou (Pap) test results that reveal the presence of low-grade squamous intraepithelial lesion (LSIL) or ASC-US. The ASCUS-LSIL Triage Study was a large, federally funded trial of alternative strategies for the initial management of mildly abnormal cytology results. Women with ASCUS or LSIL results obtained by traditional spatula and brush technique were referred to the study from community practice (n = 5,060; 3,488 women with ASC-US, 1,572 with LSIL).

All of the patients had ThinPrep cytology, HPV testing, and two cervigrams at the time of enrollment and at six, 12, and 18 months. The women were randomized into one of the following three study arms: (1) immediate colposcopy at the time of enrollment; (2) HPV triage with colposcopy only if enrollment cytology showed high-grade intraepithelial lesion (HSIL) or LSIL–ASC-US with a high-risk HPV subtype; or (3) conservative management with blinding to HPV results and colposcopy only if semiannual cytology showed HSIL.

Follow-up visits were conducted at six, 12, and 18 months in all arms with specimens obtained as they were at enrollment. Women were referred to colposcopy for HSIL cytology results. Women with cervical intraepithelial neoplasia (CIN) grades II or III diagnosed during the study were offered loop electrosurgical excision procedure (LEEP). A final assessment that included colposcopy was performed 24 months after enrollment, with the study care provider aware of all previous test results. The final assessment was used as the diagnostic gold standard. At the conclusion of the study, all of the women with CIN grades II or III underwent LEEP; those with CIN grade I and cytology results of LSIL or HPV plus ASC-US within the previous year also were offered LEEP.

The HPV triage strategy referred 55 percent of women for colposcopy and was 72 percent sensitive for diagnosing CIN grade III. A single HPV test at enrollment identified 92 percent of women diagnosed with CIN grade III at any time during the two-year study period. Serial cytology required two visits to achieve similar sensitivity (95 percent), with 67 percent of women referred for colposcopy. The immediate colposcopy group was only 54 percent sensitive, and 100 percent of the women were referred for colposcopy. In women who were referred with ASC-US, the enrollment cytology, which was obtained an average of two months later, showed ASC-US again in only 32 percent of the women. No cases of invasive carcinoma were diagnosed during the study.

Bottom Line: In women whose cervical cytology results reveal ASC-US and who test positive for high-risk types of HPV, colposcopy should be performed. If HPV testing is not positive for high-risk types, colposcopy is not necessary. (Level of Evidence: 1b)