Protecting Women Against Human Papillomavirus

Benefits of HPV Vaccination

4vHPV protects against the non-oncogenic types 6 and 11, which cause 90% of genital warts [10], and the oncogenic types 16 and 18, which cause approximately 66% of cervical cancer [5]. 9vHPV protects against another 5 oncogenic types (31, 33, 45, 52, and 58) that collectively cause approximately 80% of HPV-attributable cervical cancers in the United States [5]. Both 4vHPV and 9vHPV are licensed to prevent vaginal, vulvar, and anal cancers.

The incidence of HPV infection among female adolescents has decreased since the vaccine was introduced. The total US prevalence of the 4vHPV infection types (6, 11, 16, and 18) among female adolescents aged 14–19 years has decreased significantly—from 11.5% in the pre-vaccination era (2003–2006) to 4.3% in the post-vaccination era (2009–2012); among females aged 20–24 years, rates have decreased from 18.5% to 12.1% [11]. Among females aged 14–24 years who received the 4vHPV vaccine, the prevalence rate of the 4 HPV types was only 2.1%, compared with 16.9% among females who did not receive the vaccine [11].

HPV vaccination also prevents precancerous lesions. Pap tests detect cervical intraepithelial neoplasia (CIN) grade 2/3, which is a precancerous lesion of the cervix caused by the HPV infection. If left untreated, these lesions may evolve into cancer. Women who test positive may undergo follow-up tests such as a repeat Pap test, colonoscopy, loop electrosurgical excision procedure (LEEP), and/or conization. These tests can be uncomfortable and can weaken the cervix, potentially leading to later obstetric complications such as premature delivery and low infant birth weight [12]. Pap tests that show false-positive results for CIN 2/3 can cause undue psychological stress, repeat testing, and physical risk on healthy patients.

By preventing cervical cancer, the HPV vaccine is projected to save the United States billions of dollars in annual health care costs related to cervical cancer screening and cancer treatments. Cervical cancer screening and follow-up procedures cost the nation approximately $6.6 billion per year, which accounts for more than 80% of the total costs for preventing and treating HPV-attributable diseases. Comparatively, cancer treatments account for 12% of total HPV-attributed health care costs [13].

Research has demonstrated that the HPV vaccine is highly effective in preventing HPV infections, cancers, and precancerous lesions [14, 15]. Side effects of the vaccine most commonly include injection site reactions such as pain, erythema, and swelling [16]. The vaccine has not been demonstrated to be an attributable cause of neurodegenerative disorders including Guillain-Barré Syndrome [17]. The vaccine is contraindicated in individuals with hypersensitivity, including those who have severe allergic reactions to yeast (a vaccine component) or those who had a severe reaction after a previous dose of HPV vaccine [16].

HPV Vaccination Uptake and Disparities

National estimates suggest that 53,000 lifetime cervical cancer cases will be prevented for girls currently age 12 years and younger if the Healthy People 2020 goal of 80% vaccine coverage is met [18]. While HPV vaccination uptake rose modestly from 2014–2015, it remains low in comparison to other recommended vaccines. In 2015, 60% of females aged 13–17 years had received at least 1 dose of the HPV vaccine, although only 39.7% had received 3 or more doses. Rates for receiving the initial dose (41.7%) and for completing the series (21.6%) were lower among males in the same age group. By comparison, 87.6% of 13–17-year-old adolescents had received the Tdap vaccine, and 79.3% had received 1 or more meningococcal vaccine. North Carolina had a higher rate of HPV vaccination initiation (65.7%) for females than the US average, although rates for receiving 3 or more doses among females and rates for males are on par with the US average [9].

In the United States, Latina (68.4%) and African American (66.9%) females aged 13–17 years have higher HPV vaccination initiation rates than white females (59.2%). However, Latina females (46.2%) are more likely to have 3 or more doses than are African American (40.8%) and white (39.6%) females [9]. In younger children (aged 9–14 years), the immunogenicity of 2 doses separated by 6–12 months is higher than the immunogenicity of 3 doses for 15–26-year-olds.

The National Health and Nutrition Examination Survey found that only 32.6% of females aged 20–24 years and 14.7% of females aged 24–29 years had received 1 or more HPV vaccine doses in the 2009–2012 survey collection period. This compares to 51.4% of females aged 14–19 years who received the vaccine in the same time frame [11]. Females up to age 26 years should receive the vaccine if they did not receive it when they were younger.

Adolescents living in poverty were also more likely to initiate and complete the HPV vaccine [9]. This may be because the vaccination is free for uninsured, underinsured, and other qualifying low-income adolescents up to age 18 years through the Vaccines for Children Program.

Barriers to Uptake

A number of barriers contribute to the low uptake of HPV vaccination (see Table 2). For many parents, concerns about vaccination encouraging adolescents' earlier sexual debut and greater promiscuity are a barrier [20, 21]. Despite these fears, research shows that adolescents who received the vaccine have not had greater numbers of sexual partners than those who did not receive the vaccine [11]. Additional barriers are low perceived risk of HPV infection and lack of knowledge about HPV and the vaccine [22]. Parents also remain concerned about safety [23, 24] and effectiveness [24].

Physician recommendation is one of the most influential factors in vaccine uptake. However, studies have demonstrated that some providers do not consistently or strongly recommend the vaccine to all eligible adolescents at ages 11–12 years [22]. Physician hesitancy may be due to an over-estimation of parental objection, and physicians may not offer a strong recommendation when faced with parental reluctance [25].

Accessibility and missed opportunities are additional barriers to vaccination of adolescents. Adolescents visit physician offices less frequently than do younger children, and they are more likely to come for an acute visit, when the vaccine is less likely to be recommended than during a routine exam. This is a missed opportunity, and HPV vaccination should be offered to all eligible adolescents and young adults at all visits. Cost can also impact vaccination access [20]. However, under the Patient Protection and Affordable Care Act of 2010 and the Vaccines for Children Program, all age-eligible females and males—including those who are uninsured—should have coverage for this vaccine. Some private insurance companies may require copayments.

Evidence-Based Strategies to Increase Vaccine Initiation and Completion

Several evidence-based strategies to increase vaccine initiation and completion have been endorsed by the Centers for Disease Control and Prevention, the National Vaccine Advisory Committee, and the Advisory Committee on Immunization Practices (ACIP). One of these strategies is the Assessment, Feedback, Incentives, and eXchange (AFIX) approach. With AFIX, the state immunization branch or another external source assesses a physician's practice to evaluate vaccination coverage for specific groups and to determine strategies for improvement. Practices are then given feedback about the results of their assessment. Various incentives are used to build morale. Incentives may involve new community partnerships and opportunities for collaboration, which can lead to sharing of information and ideas across practices [26]. This strategy has been successful in North Carolina [27].

Other strategies include immunization information systems, parent recommendation and reinforcement, reminders and recall directed at providers, and reminders and recall directed at patients. Matheson and colleagues found that text-message reminders effectively increased the likelihood of adolescents receiving their second and third doses of vaccine on time [28]. Other studies have found that calls, letters, and e-mails were effective in increasing initiation and completion of HPV vaccination [29]. A combination of patient/parent reminders and physician messaging and reminders has been used to increase adolescent uptake. Notably, physician-directed reminders may be most effective for initiating the vaccine series, while parent/patient reminders can be especially useful for increasing series completion [29].

Current Recommendations

The ACIP recommends that routine HPV vaccination be initiated at age 11 or 12 years in females and males, before most adolescents' sexual debut. The immunogenicity of the vaccine (its ability to mount an immune response) is also greatest in the younger age group [8]. However, the vaccine is recommended beginning at age 9 years for children with any history of sexual abuse or assault who have not initiated or completed the series [15]. Vaccination is also recommended for females aged 13–26 years and for males aged 13–21 years who have not been previously vaccinated or who have not completed the series. Males aged 22–26 years may be vaccinated. For men who have sex with men, ACIP recommends routine HPV vaccination as for all males, and vaccination is recommended through age 26 years for those who were not adequately vaccinated previously.

The vaccine should be given even if the age-eligible young person has engaged in sexual activity, as an individual is unlikely to have contracted all the HPV types in the vaccine. They will receive protection from any types to which they have not been exposed. Vaccination of females is recommended with the 2vHPV, 4vHPV (if available), or 9vHPV vaccine. Vaccination of males is recommended with 4vHPV or 9vHPV. In October 2016, the ACIP changed dosing recommendations from a 3-dose series to a 2-dose series for adolescents initiating the series between ages 9–14 years due to higher immune response to the vaccine in this age group. Doses should be delivered 6–12 months apart. Adolescents initiating the series between ages 15–26 years continue to need the 3-dose series, which can be administered at 0, 1–2, and 6 months [30]. If the vaccine schedule is interrupted, the vaccination series does not need to be restarted [8].