The low risk of precancer after a screening result of human papillomavirus-negative/atypical squamous cells of undetermined significance papanicolaou and implications for clinical management

BACKGROUND Different US practice guidelines have conflicting recommendations for when women should return after a screening result of human papillomavirus (HPV)-negative with an equivocal Papanicolaou (Pap) result of atypical squamous cells of undetermined significance (ASC-US) (ie, return in either 3 or 5 years). One way to determine management is to compare the risk of precancer/cancer after an HPV-negative/ASC-US result with the risks after other negative screening results. For example, if the risk after an HPV-negative/ASC-US result was similar to the risk after a negative Pap test, a 3-year return would be preferred because guidelines agree that women with negative Pap test results should return in 3 years. Alternatively, if the risk after an HPV-negative/ASC-US result is similar to that after a cotest-negative result (HPV negative/Pap test negative), a 5-year return would be preferred because guidelines agree that women testing cotest negative should return in 5 years. METHODS The authors compared risks of cervical intraepithelial neoplasia of grade 3 or higher (CIN3+) and cervical cancer among women aged 30 years to 64 years at Kaiser Permanente Northern California with the following test results from 2003 through 2012: 17,191 women testing HPV negative/ASC-US; 980,268 women testing Pap test negative (regardless of HPV result); and 892,882 women testing cotest negative. RESULTS The 5-year CIN3+ and cancer risks after an HPV-negative/ASC-US result were closer to the risks after a negative Pap test result (CIN3+: 0.48% vs 0.31% [P =.0019]; and cancer: 0.043% vs 0.031% [P =.4]) than after a negative cotest (CIN3+: 0.48% vs 0.11% [P<.0001]; and cancer: 0.043% vs 0.014% [P =.016]). CONCLUSIONS Women testing HPV negative/ASC-US were found to have precancer/cancer risks that were more closely aligned with women with negative Pap test results, suggesting that women testing HPV negative/ASC-US should be managed similarly to women testing negative on Pap tests with a 3-year return for screening.