Cotesting Detects Cervical Cancers Missed by Human Papillomavirus–Only Testing in Clinical Practice [144

Abstract

INTRODUCTION: Current American College of Obstetricians and Gynecologists and American Society for Colposcopy and Cervical Pathology guidelines support the use of Pap and human papillomavirus (HPV) cotesting for cervical cancer screening in women 30 years of age and older. The U.S. Food and Drug Administration approval of an HPV test for primary cervical cancer screening in women 25 years of age and older differs from these guidelines. This Quest Diagnostics Health Trends report describes how often primary HPV screening might miss an actionable lesion. METHODS: We reviewed deidentified cotesting and cervical biopsy results from January 2005 to September 2011 in women 21 years and older who had undergone cervical biopsy within 1 year of cotesting. Pap test results of atypical squamous cells of undetermined significance or more severe were considered abnormal. RESULTS: Of the 455,945 women, 6,515 had cervical intraepithelial neoplasia (CIN) type 3 or more severe lesions, including 587 cancers. As expected, cotesting was positive (ie, HPV-positive or abnormal Pap test results) in most women with CIN 3+ lesions (6,469 of 6,515 [99.3%]), including those with cancer (558 of 587 [95.1%]). However, HPV was negative in 295 of 6,515 (4.5%) women with CIN 3+ and 109 of 587 (18.6%) women with cancer. In HPV-negative women, Pap testing showed abnormal results in 249 of 295 (84%) with CIN 3+ lesions, including 80 of 109 (73%) with cancer. CONCLUSION: This retrospective, longitudinal analysis suggests that primary HPV testing alone would have missed detection of 4.5% of CIN 3+ lesions identified by cotesting (including 18.6% of cancers). Pap test results would have prompted further evaluation in a significant proportion of women with HPV-negative CIN 3+ pathology. These findings, supporting cotesting, may have implications for an individual woman's choice, guideline development, and legal risk.