What Would We Miss if HR-HPV Testing Was Used for Primary Cervical Cancer Screening

Introduction: The US Food and Drug Administration (FDA) recently approved use of the Cobas HPV test (Roche Molecular System, Pleasanton CA) for primary cervical cancer screening in women 25 years or older. False-negative high risk (HR) human papillomavirus (HPV) results can become clinically relevant when used independent of cytology for primary screening. This study investigates the occurrence and significance of abnormal cytology and negative HR HPV testing with the Cobas HPV system in ThinPrep (Hologic, Bedford MA) and SurePath (BD, Burlington NC) preparations. Materials and Methods: All liquid-based Pap tests with negative HR HPV co-testing performed using the Cobas HPV system in women 25 years or older between August 2012 and July 2013 were retrieved. Pathologic follow-up was evaluated when available. Results: A total of 24,384 liquid-based Pap tests with negative HR HPV co-testing from women 25 years or older were evaluated. Overall, abnormal cytology (ASCUS or above) was noted in 1,015 cases (4.2%) as outlined in Table 1. Follow-up was available in 603 (59.4%) women: 150 (24.9%) were found to have significant uterine lesions (CIN 1+), including 9 (1.5%) with CIN 2+ squamous lesions, 3 endometrial simple hyperplasias, 4 (0.6%) endometrial adenocarcinomas, and 1 fallopian tube adenocarcinoma. All 5 women who on follow up were found to have uterine adenocarcinoma were asymptomatic. In addition, of 838 (5.1%) women aged 40 or older with endometrial cells noted by cytology, 4 (0.5%) were diagnosed with endometrial adenocarcinoma on subsequent follow-up. Conclusions: Using CIN 2+ as the cutoff, 1.5% of women would have a significant HPV-related uterine lesion that would have gone undetected if HR HPV testing was used alone as the primary screening test. Therefore, while HR HPV testing is sensitive in detecting HPV-related precancerous and cancerous lesions, a small percentage of non-HPV related uterine malignancies would go undetected.