More than 15% of cancers worldwide are due to an infectious agent and approximately one-third of these are caused by the human papillomavirus (HPV).1 HPV is considered the most significant oncogenic virus infecting humans and has been identified as a mediator for anogenital cancers including vulvar, vaginal, cervical, penile, and anal cancers; it is also associated with oropharyngeal cancer and genital warts.2

Despite reassuring safety data from clinical trials involving >15,000 patients,3 the use of the inactivated HPV vaccine in the United States remains low. Recent estimates from the 2018 National Immunization Survey showed that only 53.7% of girls and 48.7% of boys aged 13 to 17 years received all the recommended doses of the vaccine.4 Despite a modest increase in coverage since 2011, these numbers fall well below the Centers for Disease Control and Prevention’s (CDC) Healthy People 2020 target of 80% coverage.5

With recent changes in the US Food and Drug Administration (FDA) approval for 9-valent HPV vaccine (9vHPV, Gardasil 9), as well as the updated recommendations from the CDC’s Advisory Committee on Immunization Practices (ACIP),6 it is vital that healthcare providers feel confident in their encouragement of vaccination in appropriate patient population and their parents.

Human Papillomavirus

Human papillomavirus is a member of the Papillomaviridae family, a group of viruses with a small, double-stranded DNA circular genome.7 These viruses have been discovered in the fossil remains of Actinopterygii dating from more than 420 million years ago.1 Of the 49 genera within the Papillomaviridae family, 5 encompass more than 200 individual subtypes that infect humans, the majority of which cause benign, asymptomatic infections.7 Of the genera, 4 infect cutaneous epithelia and the fifth, the alpha genus, has an affinity for cutaneous and mucosal epithelia and includes the 12 “high-risk” oncogenic HPV subtypes.7 The International Agency for Research on Cancer (IARC) has recently identified an additional subtype that is categorized as either probably, or possibly, carcinogenic.8

The affinity of HPV for infecting cutaneous and mucosal epithelia allows the virus to persist in the host for a long time. The virus infects the basal layer of the epithelium through  microabrasion and infects self-renewing cells. This cycle allows the virus to restrict high levels of viral protein production to differentiated layers of squamous epithelia, which is believed to help it elude detection by the immune system.7 

Most sexually active individuals will acquire at least 1 type of HPV infection at some point during their lives. The 2 most high-risk oncogenic genotypes, HPV16 and HPV18, are also the most common worldwide. Infection with HPV16 and HPV18 have been associated with 72% of all HPV-associated cancers worldwide.9 Table 1 presents the estimated number of cancer cases in the United States attributable to HPV by sex, site of cancer, and HPV type.10 In 2018, the CDC reported that 42,700 new cases of HPV-associated cancers occur in the United States each year; approximately 24,400 in women and 18,300 in men.10 The incidence of HPV-associated cancers varied by cancer type, gender, and race/ethnic group; however, cervical cancer remained the most common in women, with oropharyngeal cancer the most common in men.

Table 1. Estimated Number of HPV-Associated Cancer Cases10

Site of Cancer HPV 16, 18, N HPV 31,33,45,52,58, N HPV other types, N
Cervix 7900 1700 1200
Vagina 500 100
Vulva 1900 600 200
Anus* (f) 3400 500 100
Oropharynx (f) 1700 300 200
Penis 600 100 100
Anus* (m) 1700 100 100
Oropharynx (m) 9400 700 600

* Includes anal and rectal squamous cell carcinomas.

New Vaccination Schedule

The inactivated HPV vaccine (Gardasil®) was first approved by the FDA in 2006 to prevent cancers and infections caused by 4 HPV types; however, it is no longer available in the United States.11 In 2014, the FDA approved 9vHPV for both men and women ≤26 years of age. The vaccination contains 7 oncogenic HPV types (16, 18, 31, 33, 45, 52, and 58) and 2 HPV types that cause most genital warts (6 and 11).12 The target age for vaccination is between 11 and 12 years of age, but the vaccine is approved for use in girls and boys starting at age 9.6

There has been consistent evidence that a 2-dose schedule for adolescents (age 9 to 14 years) evokes a similar immunologic response compared with a 3-dose regimen in women (16 to 26 years).12-15 In 2014, the European medical associations recommended reducing the vaccination schedule for adolescents to 2 doses; the FDA followed suit in 2016.13 Consequently, the recommended timing of the vaccine is 0 (baseline) and 6 to 12 months later. If the interval between doses is <5 months, it is recommended that the patient receive a third dose. If the first dose is given after age 15, a 3-dose schedule is recommended at 0 (baseline), 1 to 2 months, and 6 months after the first dose (Table 2).16

Table 2. Recommended HPV Vaccination Schedule by Age16

Age Dose schedule Interval
9 to 14 years 2-dose 0 (baseline) and 6 to 12 months later (minimum interval: 5 months; repeat dose if administered too soon)
15 to 26+ years 3-dose 0 (baseline), 1 to 2 months, and 6 months later (minimum intervals: dose 1 to dose 2: 4 weeks; dose 2 to dose 3: 12 weeks; dose 1 to dose 3: 5 months; repeat dose if administered too soon)