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BACKGROUND  In the United States, human papillomavirus (HPV) and Papanicolaou (Pap) testing ( cotesting ) for cervical screening in women ages 30 to 65 years is the preferred strategy, and cytology alone is acceptable. Recently, a proprietary automated test for identifying high‐risk HPV types for primary cervical screening was approved by the US Food and Drug Administration. The objective of the current study was to document extensive cervical screening among these screening options.    METHODS  To investigate the sensitivity of various testing options for biopsy‐proven cervical intraepithelial neoplasia grade 3 or worse (≥CIN3) and cancer, the authors reviewed 256,648 deidentified results from women ages 30 to 65 years at the time of cotest who had a cervical biopsy specimen obtained within 1 year of the cotest.    RESULTS  A positive cotest result was more sensitive (98.8%; 4040 of 4090 cotests) for diagnosing ≥CIN3 than either a positive HPV‐only test (94%; 3845 of 4090 HPV‐only tests) or a positive Pap‐only test (91.3%; 3734 of 4090 Pap‐only tests;  P  < .0001). A positive Pap‐only result was more specific (26.3%; 66,145 of 251,715 Pap‐only tests) for diagnosing ≥CIN3 than a positive HPV‐only test (25.6%; 64,625 of 252,556 HPV‐only tests) or a positive cotest (10.9%; 27,578 of 252,558 cotests;  P  < .0001). Of 526 cervical cancers, 98 (18.6%) were HPV‐only negative, 64 (12.2%) were Pap‐only negative, and 29 (5.5%) were cotest negative.    CONCLUSIONS  Compared with HPV‐only testing, cotesting was more sensitive for the detection of ≥CIN3 in women ages 30 to 65 years. The current data suggest that approximately 19% of women with cervical cancer may be misdiagnosed by an HPV‐only cervical screen. It is important to consider these data as the guidelines for cervical cancer screening undergo revision.   Cancer (Cancer Cytopathol)  2015;123:282–8 . © 2015 The Authors.  Cancer Cytopathology  published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

Comparison of cervical cancer screening results among 256,648 women in multiple clinical practices