Trends in cervical intraepithelial neoplasia Grade 2+ after human papillomavirus vaccination: The devil is in the details

In June 2006, the Food and Drug Administration approved the human papillomavirus virus (HPV) quadrivalent vaccine against HPV-6, HPV-11, HPV-16, and HPV-18, the types responsible for 70% of cervical cancers (HPV-16 and HPV18) and 90% of genital warts (HPV-6 and HPV-11). In October 2009, a second bivalent vaccine against HPV-16 and HPV-18 was approved. These 2 vaccines have since been offered as part of adolescent vaccination programs (targeting 9to 12-year-olds) and as part of short-term catch-up vaccination programs targeting older age groups (13to 26-year-olds). Because of the long lead time between HPV infection and the development of invasive cervical cancer, the impact of HPV vaccination on the incidence of cervical cancer will take another decade to ascertain. However, as the vaccinated cohort enters adulthood, 8 years since the introduction of the first vaccine, the impact of these vaccination programs is now being assessed through surrogate markers such as the incidence of high-grade cervical dysplasia (cytology/histology) and the incidence of genital warts. In the current issue of Cancer, using data from the first 5 years of the Human Papillomavirus Vaccine Impact Monitoring Project (HPV-IMPACT), a project initiated in 2008 to monitor the impact of HPV vaccinations on the incidence of CIN21 abnormalities through population-based laboratory surveillance, Hariri et al report on trends in cervical intraepithelial neoplasia grade 21 (CIN21) diagnosis rates in different geographic areas in the United States. The authors are to be congratulated for successfully collecting and analyzing data from a variety of sources. Unfortunately, the analysis of these data is complicated by the fact that cervical cancer screening guidelines have undergone significant changes over the last few years, with progressive increases in both the age of initiating screening and the screening interval itself. This study is significant in that it is the first ecological study to look at trends in CIN21 diagnosis rates in the postvaccination era in the context of changing cervical cancer screening guidelines. The study highlights that although preliminary data demonstrate a drop in CIN21 incidence rates, the results may be confounded by the changes in cervical screening guidelines. Prior to 2012, there were significant differences between the cervical cancer screening guidelines issued by the American Congress of Obstetrics and Gynecologists, the American Cancer Society, and the US Preventive Services Task Force. The most significant differences related to the age of the initiation of Papanicolaou screening, the frequency of screening, and the use of HPV DNA testing. The previous guidelines also allowed Papanicolaou screening to be initiated in patients younger than 21 years if they had been sexually active for more than 3 years. Because of the discordance among the guidelines, there was significant heterogeneity in patient care. A 2002 Centers for Disease Control and Prevention provider survey showed that 50% of providers were screening 18-year-old virgins, and 80% were screening 18-year-olds who had initiated sex within the last month. When asked about cervical cancer screening, 60% of women who had initiated sex less than 3 years ago reported that they had had cervical cancer screening. As data began to accrue about the high prevalence and high clearance rate of HPV infections in young women, the question of when to begin screening was finally addressed at the 2009 Practice Improvement in Cervical Screening and Management (PICSM) symposium. The new recommendations increased the age at which to initiate screening to 21 years. In 2012, the American Cancer Society and the American Society for Colposcopy and Cervical Pathology issued their updated guidelines, and these have been formally endorsed by the American Congress of Obstetrics and Gynecologists and the US Preventive Services Task Force. The new unified guidelines recommend that 1) Papanicolaou screening not be used for women aged< 21 years, regardless of the initiation of sexual activity, and 2) a screening interval of 3 years be maintained for women aged 21 to 30 years. Even though the new