Infection with high-risk human papillomavirus (hrHPV) is an essential step in the development of cervical cancer and its precursors, as well as in several other cancers, including oropharyngeal, vulvar, vaginal, anal, and penile cancers. At least 13 HPV strains, known collectively as hrHPV, have been associated with cervical cancer, in addition to more than 150 low-risk HPV types that have not been associated with cancer (for example, HPV 6 and 11).1 Up to 80% of women (and most men, although men are not tested routinely) will become infected with at least one of the high-risk HPV types throughout their lives, although in most cases these infections will be transient and have no clinical impact for the patient. Patients who test positive consecutively over time for hrHPV, and especially those who test positive for one of the most virulent HPV types (HPV 16 or 18), have a higher risk of developing cervical cancer or precancer. In addition, many patients who acquire HPV at a young age may “clear” the infection, which usually means that the virus becomes inactive; however, often, for unknown reasons, the virus can be reactivated in some women later in life.
This knowledge of the natural history of HPV has led to improved approaches to cervical cancer prevention, which relies on a combined strategy that includes vaccinating as many children and young adults as possible against hrHPV, screening and triaging approaches that use HPV-based tests, and applying risk-based evaluation for abnormal screening results. New guidelines and information address the best approaches to each of these aspects of cervical cancer prevention, which we review here.
HPV vaccination: Recommendations and effect on cervical cancer rates
Meites E, Szilagyi PG, Chesson HW, et al. Human papillomavirus vaccination for adults: updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2019;68:698-702.
Lei J, Ploner A, Elfstrom KM, et al. HPV vaccination and the risk of invasive cervical cancer. N Engl J Med. 2020;383;1340-1348.
Vaccination at ages 27 to 45, although approved by the US Food and Drug Administration, is recommended only in a shared decision-making capacity by ACIP and the American College of Obstetricians and Gynecologists (ACOG) due to the vaccine’s minimal effect on cancer prevention in this age group. The ACIP and ACOG do not recommend catch-up vaccination for adults aged 27 to 45 years, but they recognize that some who are not adequately vaccinated might be at risk for new HPV infection and thus may benefit from vaccination.4
In contrast, the American Cancer Society (ACS) does not endorse the 2019 ACIP recommendation for shared clinical decision making in 27- to 45-year-olds because of the low effectiveness and low cancer prevention potential of vaccination in this age group, the burden of decision making on patients and clinicians, and the lack of sufficient guidance on selecting individuals who might benefit.5
Decline in HPV infections
A study in the United States between 2003 and 2014 showed a 71% decline in vaccine-type HPV infections among girls and women aged 14 to 19 in the post–vaccine available era as compared with the prevaccine era, and a lesser but still reasonable decline among women in the 20- to 24-year-old age group.6 Overall, vaccine-type HPV infections decreased 89% for vaccinated girls and 34% for unvaccinated girls, demonstrating some herd immunity.6 Ideally, the vaccine is given before the onset of skin-to-skin genital sexual activity. Many studies have found the vaccine to be safe and that immunogenicity is maintained for at least 9 years.7-11
Decrease in invasive cervical cancer
Recently, Lei and colleagues published a study in the New England Journal of Medicine that reviewed outcomes for more than 1.6 million girls and women vaccinated against HPV in Sweden between 2006 and 2017.12 Among girls who were vaccinated at younger than 17 years of age, there were only 2 cases of cancer, in contrast to 17 cases among those vaccinated at age 17 to 30 and 538 cases among those not vaccinated.
This is the first study to show definitively the preventive effect of HPV vaccination on the development of invasive cancer and the tremendous advantage of vaccinating at a young age. Nonetheless, the advantage conferred by catch-up vaccination (that is, vaccinating those at ages 17–30) also was significant.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
Despite the well-established benefits of HPV vaccination, only 57% of women and 52% of men in the recommended age groups have received all recommended doses.13 Based on these findings, we need to advocate to our patients to vaccinate all children as early as recommended or possible and to continue catch-up vaccination for those in their 20s, even if they have hrHPV, given the efficacy of the current nonvalent vaccine against at least 7 oncogenic types. It is not at all clear that there is a benefit to vaccinating older women to prevent cancer, and we should currently focus on vaccinating younger people and continue to screen older women as newer research indicates that cervical cancer is increasing among women older than age 65.14
Despite the well-established benefits of HPV vaccination, only 57% of women and 52% of men in the recommended age groups have received all recommended doses.13 Based on these findings, we need to advocate to our patients to vaccinate all children as early as recommended or possible and to continue catch-up vaccination for those in their 20s, even if they have hrHPV, given the efficacy of the current nonvalent vaccine against at least 7 oncogenic types. It is not at all clear that there is a benefit to vaccinating older women to prevent cancer, and we should currently focus on vaccinating younger people and continue to screen older women as newer research indicates that cervical cancer is increasing among women older than age 65.14
Continue to: Updated guidance on cervical cancer screening for average-risk women...