Rates of cancers attributable to human papillomavirus (HPV) are rising. A safe and extremely effective vaccine is available to prevent many of these cancers. Studies have shown that health care providers’ recommendation to immunize is the most important factor in parents’ decision. Parents of all adolescent boys and girls should receive a strong and unequivocal recommendation to vaccinate their child against HPV at the 11- or 12-year-old well child visit. Ideally, adolescents complete their HPV vaccine series by their 13th birthday, leading to greater immune response and protection before most adolescents are exposed to sexually transmitted HPV.
Key points
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Cancers attributable to human papillomavirus (HPV) are on the rise.
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Vaccine against the 7 HPV types that cause 73% of HPV-associated cancers is available, safe, and very effective.
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Vaccine also protects against the 2 HPV types that cause 90% of genital warts.
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The health care provider’s recommendation to vaccinate is among the most important determinants of whether a teen receives the HPV vaccine.
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HPV vaccine should be recommended at the 11- or 12-year-old well-child visit and the series should be completed by the 13th birthday.
Introduction
There are more than 120 different types of human papillomavirus (HPV). Most are responsible for warts found on the skin. Approximately 40 HPV types infect mucosal surfaces and the genital tract, and 13 of these are oncogenic. This article examines the epidemiology and strategies to control the spread of the most common and most serious HPV types for which preventive vaccines are available.
Introduction
There are more than 120 different types of human papillomavirus (HPV). Most are responsible for warts found on the skin. Approximately 40 HPV types infect mucosal surfaces and the genital tract, and 13 of these are oncogenic. This article examines the epidemiology and strategies to control the spread of the most common and most serious HPV types for which preventive vaccines are available.
Epidemiology
Approximately 79 million people in the United States are infected with HPV, and 14 million acquire a new infection each year. In 1 study measuring HPV prevalence just before introduction of a quadrivalent HPV vaccine in 2006, 33% of 14- to 19-year-old female patients and 54% of 20-to 24-year-old female patients were infected with genital HPV.
A systematic review published in 2006 included numerous HPV prevalence studies among men but most studies did not stratify by age. The prevalence in the 8 studies conducted in university or military settings ranged from 10% to 40%. The US cohort of men enrolled into the Human Papillomavirus in Men study had a prevalence of 23% for 15- to 19-year-old, 10% for 25- to 29-year-old, and 37% for 20- to 24-year-old men.
There are differences in race and ethnicity among those who develop HPV-related cancers. For example, Hispanic and black women experience higher rates of cervical cancer than white women, and American Indian or Alaska Native and Asian or Pacific Islander women experience the lowest rates. It is not clear whether these differences are due to access to care and screening issues, innate genetic differences of HPV hosts based on race, or intratypic HPV variants circulating in different community populations. More study is needed.
Pathophysiology and natural history
Most HPV infections have no symptoms and are cleared by the host immune system, usually within 1 to 2 years. However, viral shedding occurs even when no visible lesions are present. Although condoms can prevent transmission of HPV, contact frequently occurs at sites that are not protected by the condom barrier. HPV can also be spread by nonsexual skin-to-skin contact. Therefore, even when partners consistently use condoms, viral transmission can occur.
HPV 6 and 11 are the types that account for approximately 90% of cases of genital warts. Although the HPV types that cause genital warts are nononcogenic, there can still be significant morbidity associated with the development of genital warts, most notably psychological distress as a result of both the appearance and the recurrence of genital warts.
When any of the 13 sexually transmitted oncogenic HPV types persist, precancer and cancer can develop. The time between infection and development of cancer is generally at least 15 years and can be up to 25 years or more. HPV 16 is the type most likely to persist and, therefore, to cause cancer. Immunocompromised individuals, such as those with human immunodeficiency virus (HIV) infection or those who take immunosuppressive medication, are at higher risk for HPV persistence.
Burden of disease
Sexually transmitted HPV-associated cancers include cancers of the cervix, vulva, vagina, penis, oropharynx, anus, and rectum. Oropharyngeal cancers include cancers of the base of the tongue, the pharyngeal tonsils and tonsillar pillars, the anterior surface of the soft palate and uvula, and the lateral and posterior pharyngeal walls.
Analysis of 2008 to 2012 data from the Centers for Disease Control and Prevention’s (CDC’s) National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results program provides estimates of cancers attributable to HPV. Using information from polymerase chain reaction genotyping studies, the investigators calculated the proportion of HPV-associated cancers that were attributable to an oncogenic HPV type. Of the 30,100 cancers attributable to HPV from 2008 to 2012, 18,700 were in female patients and 11,400 were in male patients ( Table 1 ). These data also demonstrated an increase in HPV-related cancers compared with 26,000 diagnoses per year during 2004 to 2008.
| Cancer | Average Number of HPV-Associated Cancers | Average Number of Cancers Attributable to HPV | ||
|---|---|---|---|---|
| Female | Male | Female | Male | |
| Anal | 3260 | 1750 | 3000 | 1600 |
| Cervical | 11,771 | 0 | 10,700 | 0 |
| Oropharyngeal | 3100 | 12,638 | 2000 | 9100 |
| Penile | 0 | 1168 | 0 | 700 |
| Vaginal | 802 | 0 | 600 | 0 |
| Vulvar | 3554 | 0 | 2400 | 0 |
| Total | 22,487 | 15,556 | 18,700 | 11,400 |
The American Cancer Society estimates that 12,990 new cases of invasive cervical cancer will be diagnosed in the United States in 2016 and 4120 women will die from cervical cancer. For vulvar cancer, the estimates are 5950 women will be diagnosed and 1110 women will die. For anal cancer, the estimates are 8080 new cases and 1080 deaths. The CDC estimates that 9000 new cases of oropharyngeal cancer due to HPV occur each year, with 4 times as many of these cancers occurring in men than in women. The 5-year survival rate for oropharyngeal cancer is 85% to 90%.
Data from the early 2000s suggest that the annual incidence of anogenital warts is approximately 225 per 100,000, and equally distributed between men and women. It is estimated that 1.2 per 1000 female patients and 1.1 per 1000 male patients have acquired genital warts, with the peak incidence in women occurring between the ages of 20 to 24 years and the peak incidence in men occurring between 25 to 29 years.
Available vaccines for prevention
Before 2017, there were 3 types of vaccine available to protect against HPV in the United States: bivalent (2vHPV), quadrivalent (4vHPV), and 9-valent (9vHPV) ( Table 2 ). All 3 vaccines protect against HPV types 16 and 18, which cause 63% of HPV-associated cancers in the United States. Although 2vHPV and 4vHPV vaccines are still available outside of the United States, currently only the 9-valent product is used in the Unites States. The 4vHPV and 9vHPV vaccines protect against HPV types 6 and 11, which cause 90% of genital warts. The 9-valent vaccine, licensed in 2015, includes protection against 5 additional oncogenic HPV types that cause an additional 10% of HPV-associated cancers in the United States.
| Bivalent (Ceravix) | Quadrivalent (Gardasil) | 9-Valent (Gardasil-9) | |
|---|---|---|---|
| Manufacturer | GlaxoSmithKline | Merck | Merck |
| HPV types | 16, 18 | 6, 11, 16, 18 | 6, 11, 16, 18, 31, 33, 45, 52, 58 |
| Recommended age a | Female patients 11–26 y | Female patients 11–26 y Male patients 11–21 y b | Female patients 11–26 y Male patients 11–21 y b |
a HPV vaccine may be given as young as age 9 years.
b Immunization through age 26 years is recommended for men who have sex with men; men who are immunocompromised, including infection with HIV; and all men desiring protection against HPV.
The Advisory Committee on Immunization Practices (ACIP) recommends that adolescents begin the HPV vaccination series at age 11 to 12 years (see Table 2 ) and complete the series by their 13th birthday. The vaccine is most effective when administered before initiation of sexual activity because the vaccines are preventive only and do not treat or cure HPV infection that has already occurred nor dysplasia or cancer that has developed in response to HPV infection. The vaccine may be administered as early as 9 years of age. The vaccination series should be administered routinely to young men through the age of 21 years who have not previously received the vaccine. Men having sex with men, men who are immunocompromised, and all men desiring protection from HPV infection should receive the vaccination series through the age of 26 years. All young women through age 26 years who have not previously been vaccinated should receive the vaccination series. For those who initiate the series at age 9 through 14 years of age, a 2-dose series is administered with the second dose 6 to 12 months after the first dose; for those 15 years of age or older at the time of the first dose, a 3-dose series is recommended. When giving the 3-dose series, the second dose should be given 2 months following the first dose, with a minimum interval of 4 weeks between doses 1 and 2. The third dose should be given at least 24 weeks after the first dose and at least 12 weeks after the second dose ( Table 3 ).
