The Changing Face of Cervical Cancer Screening in the United States

Abstract

With the introduction of widespread Pap smear screening starting in the 1940s, the United States has seen at least a 50% reduction in the incidence and mortality of invasive cervical cancer. In light of the ease of sampling, the long pre-malignant phase of cervical cancer, and well-tolerated treatment options for pre-invasive disease, cervical cancer screening has served as a model for screening for other malignancies. For some women, it also serves as the cornerstone for annual routine visits with gynecologists. Both patients and gynecologists have been taught that a yearly Pap test is important, and it can serve as the backbone of care. Unfortunately, however, access to screening and treatment for cervical cancer continues to be an issue for some women in the United States. Approximately 60% of women with invasive cancer had not undergone a Pap test in the 5 years preceding their diagnosis or have never undergone a Pap test. 1 The long history of Pap tests has also taught us a number of lessons. We have learned that cytologic screening is hardly perfect. In a study by Nanda et al. 2 the sensitivity of a single test was 51%, and this was subsequently confirmed in a pooled analysis of European and Canadian studies by Cuzick et al. 3 One way to compensate for this poor sensitivity is by using serial screening; the sensitivity of cytology increases to 76% with 2 consecutive annual Pap tests and 88% with 3 consecutive tests. Just adding tests and procedures, however, is not always the answer, and most recently the pendulum has swung in the other direction. We now understand the risk of overtreating pre-invasive disease and the potential impact of overtreatment on preterm labor and neonatal morbidity and mortality. In many adolescents and young women, abnormal Pap tests and underlying disease will resolve spontaneously. Therefore, in 2009, the American College of Obstetricians and Gynecologists recommended that screening for cervical cancer start at age 21. 4 Another lesson learned is the role of human papillomavirus (HPV) in cervical cancer. High-risk (HR) HPV DNA testing has become a mainstay of cervical cancer screening over the past 10 years. Experts now recognize that more than 99% of all invasive cervical cancers are associated with 14 different HR HPV types. Currently, HR HPV testing is recommended for women with equivocal Pap tests (ASC-US) and atypical glandular Pap tests (AGC). Most importantly, it is also widely recommended in conjunction with Pap testing in women older than 30 years of age. In keeping with the lesson of not overtreating and overscreening, after negative Pap and HPV test results, an individual woman can increase her screening interval to every 3 years. Another benefit of HR HPV testing is its much higher sensitivity than Pap testing (96% vs. 53% in pooled estimates). Since 2005, 7 randomized controlled trials 5–11 have been published that evaluated HPV testing in the screening setting. These studies have largely shown improvements in the detection of pre-invasive lesions either alone or in conjunction with Pap testing. Of particular note, a recently published trial from Finland showed