Chengquan Zhao1, Zaibo Li, Ritu Nayar, Angelique W Levi, Barbara A Winkler, Ann T Moriarty, Güliz A Barkan, Jianyu Rao, Fern Miller, Fang Fan, Zhongren Zhou, Qiusheng Si, Andrew H Fischer, Charles D Sturgis, Xin Jing, Carrie B Marshall, Benjamin L Witt, George G Birdsong, Barbara A Crothers. 1. From the Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (Drs Zhao and Li); the Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (Dr Nayar); the Department of Pathology, Yale School of Medicine, New Haven, Connecticut (Dr Levi); the Department of Pathology, Mount Kisco Medical Group PC, Mount Kisco, New York (Dr Winkler); the Department of Esoteric Testing, AmeriPath, Indianapolis, Indiana (Dr Moriarty); the Department of Pathology, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois (Dr Barkan); the Department of Pathology & Laboratory Medicine, University of California, Los Angeles (Dr Rao); the Department of Pathology, Metropolitan Pathologists PC, Lakewood, Colorado (Ms Miller); the Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City (Dr Fan); the Department of Pathology and Laboratory Medicine, University Rochester Medical Center, Rochester, New York (Dr Zhou); the Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York (Dr Si); the Department of Pathology, University of Massachusetts Memorial Medical Center, Inc, Worcester (Dr Fischer); Providence Regional Medical Center, Everett, Washington (Dr Sturgis); the Department of Pathology, University of Michigan, Ann Arbor (Dr Jing); the Department of Pathology, University of Colorado, Anschutz Medical Campus, Aurora (Dr Marshall); the Department of Pathology, University of Utah, Salt Lake City (Dr Witt); the Department of Pathology & Laboratory Medicine, Emory University School Medicine, Atlanta, Georgia (Dr Birdsong); and the Department of Pathology, Walter Reed National Military Medical Center, Bethesda, Maryland (Dr Crothers).
Abstract
CONTEXT: Persistent high-risk human papillomavirus (hrHPV) infection is essential for the development of cervical cancer and its precursor lesions. High-risk HPV testing has a higher sensitivity than cytology does for detecting cervical epithelial lesions. However, a large study from a single institution showed 31% of patients with invasive cervical cancer had negative baseline hrHPV testing within 5 years preceding the diagnosis. OBJECTIVE: To investigate the limitation of hrHPV testing in detecting invasive cervical cancer. DESIGN: Cases from 2012 with a histologic diagnosis of invasive cervical carcinoma were retrieved from multiple institutions. From those records, prior hrHPV testing and Papanicolaou test results in the 5 years before the cancer diagnosis were recorded. RESULTS: Seventy patients with cervical carcinoma were included in the study. Negative HPV test result rates were 9% (5 of 53), 23% (6 of 26), and 25% (2 of 8) during the periods of less than 1 year, 1 to 3 years, and 3 to 5 years before the histologic diagnoses, respectively. Negative Papanicolaou testing results in the same time intervals were 3.4% (2 of 59), 33% (10 of 30), and 40% (6 of 15). Although the HPV(-) rate seemed to be different among different HPV test methods, no statistical significance was detected because of small sample size. Negative hrHPV rates in patients with adenocarcinoma were similar to those in patients with squamous cell carcinoma. CONCLUSIONS: These data expose limitations for the potential use of primary HPV testing. In addition, current screening guidelines recommending cotesting at 5-year intervals should be evaluated further with additional historic data collection because there are women with negative results for both Papanicolaou tests and hrHPV testing within the period of 3 to 5 years before an invasive carcinoma diagnosis.
CONTEXT: Persistent high-risk human papillomavirus (hrHPV) infection is essential for the development of cervical cancer and its precursor lesions. High-risk HPV testing has a higher sensitivity than cytology does for detecting cervical epithelial lesions. However, a large study from a single institution showed 31% of patients with invasive cervical cancer had negative baseline hrHPV testing within 5 years preceding the diagnosis. OBJECTIVE: To investigate the limitation of hrHPV testing in detecting invasive cervical cancer. DESIGN: Cases from 2012 with a histologic diagnosis of invasive cervical carcinoma were retrieved from multiple institutions. From those records, prior hrHPV testing and Papanicolaou test results in the 5 years before the cancer diagnosis were recorded. RESULTS: Seventy patients with cervical carcinoma were included in the study. Negative HPV test result rates were 9% (5 of 53), 23% (6 of 26), and 25% (2 of 8) during the periods of less than 1 year, 1 to 3 years, and 3 to 5 years before the histologic diagnoses, respectively. Negative Papanicolaou testing results in the same time intervals were 3.4% (2 of 59), 33% (10 of 30), and 40% (6 of 15). Although the HPV(-) rate seemed to be different among different HPV test methods, no statistical significance was detected because of small sample size. Negative hrHPV rates in patients with adenocarcinoma were similar to those in patients with squamous cell carcinoma. CONCLUSIONS: These data expose limitations for the potential use of primary HPV testing. In addition, current screening guidelines recommending cotesting at 5-year intervals should be evaluated further with additional historic data collection because there are women with negative results for both Papanicolaou tests and hrHPV testing within the period of 3 to 5 years before an invasive carcinoma diagnosis.
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