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

<jats:sec><jats:title>BACKGROUND</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>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% [<jats:italic>P =</jats:italic>.0019]; and cancer: 0.043% vs 0.031% [<jats:italic>P =</jats:italic>.4]) than after a negative cotest (CIN3+: 0.48% vs 0.11% [<jats:italic>P</jats:italic><.0001]; and cancer: 0.043% vs 0.014% [<jats:italic>P =</jats:italic>.016]).</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS</jats:title><jats:p>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.<jats:bold><jats:italic>Cancer (Cancer Cytopathol)</jats:italic>2014;122:842–850</jats:bold>. ©<jats:italic>2014 American Cancer Society</jats:italic>.</jats:p></jats:sec>