Toward Objective Cervical Cancer Screening

Abstract

Several years ago, I wrote an editorial for the Journal entitled, “Toward Objective Quality Assurance: The Eyes Don’t Have It.”1 The point of that commentary was to clarify some of the confusion over the relative utility of visual rescreening methods for quality control in the cytopathology laboratory that are often highly subjective and limited by issues of selection bias. In contrast, what was advocated in that editorial was the use of human papillomavirus (HPV) testing as an independent and objective quality assurance metric for assessing diagnostic interpretations. In the last decade, HPV testing has become the standard care for clinical triage of equivocally abnormal Papanicolaou (Pap) smears. Implicit in its use is the fact that in any population, HPV testing has a significantly higher sensitivity than a single Pap smear for the detection of prevalent cervical intraepithelial neoplasia (CIN) grade 3. Multiple retrospective or cross-sectional studies, authoritative meta-analyses, and, now, randomized control trials have confirmed this fact.2 However, one of the main criticisms of HPV testing is that despite its CIN 3 sensitivity, which drives the entire clinical decision-making process, HPV tests are often criticized for somewhat lower specificity when compared with cytology. Of course it is almost impossible for a test to have terrific sensitivity and spectacular specificity at the same time. Thus, while a single high-risk HPV test will identify approximately 95% of prevalent CIN 3, it still refers at least twice as many people to colposcopy as may truly have clinically significant disease detectable within any reasonable period of follow-up. The reasons for the superior sensitivity of HPV testing have been widely speculated. The arguments usually include the fact that …