Optimizing HPV vaccination

Human papillomavirus (HPV) is the most common sexually transmitted infection. Exposure is widespread and most individuals clear the infection without symptoms or development of disease. However, a subset of individuals experience persistent infection, a state which can lead to carcinogenesis of lower genital tract malignancies, particularly cervical cancer.¹

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The presence of an identifiable infectious carcinogen as the etiology for these cancers provides a unique opportunity to prevent these malignancies through vaccination programs. Fortunately, there is a vaccine available that is highly effective. However, in the United States, its benefits are severely hampered by poor rates of vaccination initiation and completion. In this column, we will review some of the important concepts in understanding the HPV vaccine and strategies to maximize the number of women who complete vaccination.
 

Vaccine coverage

Persistent infection with high-risk (oncogenic) HPV is well known to be the cause of cervical cancer. There are two HPV vaccines manufactured for the purposes of cervical cancer, anal cancer, and genital wart prevention (Cervarix and Gardasil). The Cervarix vaccine covers high-risk HPV subtypes 16 and 18 and the Gardasil vaccine prevents both low-risk HPV subtypes 6 and 11, which can cause genital warts, and high-risk HPV subtypes 16, 18, 31, 33, 45, 52 and 58, which cause cervical dysplasia and cancer.

High-risk HPV is also associated with head and neck, vulvar, vaginal, and penile cancers, though the vaccines are not approved by the Food and Drug Administration for prevention of these diseases.²

Vaccination indications

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Females and males aged 9-26 years should be offered and receive vaccination. Ideal timing is ages 9-11 years, with catch-up vaccination until age 26, according to the Centers for Disease Control and Prevention. Although it is ideal to vaccinate children at a young age and prior to sexual activity, there is a benefit to vaccination with the HPV vaccine after the onset of sexual activity and even after an abnormal pap smear result or acquisition of the virus. A history of prior vaccination is effective in reducing the likelihood of recurrence of cervical intraepithelial neoplasia (CIN) 2 or 3 after a loop electrosurgical excision procedure (LEEP).³

Since vaccination prevents multiple subtypes of HPV, an individual who has already been exposed will still benefit from protection from other subtypes of HPV through vaccination. HPV vaccination is not approved during pregnancy but can be initiated in the postpartum period when women are engaged in their health care and receiving other vaccinations, such as varicella or the MMR vaccine.

Recommended schedule

Until October 2016, the vaccination schedule was based on a three-dose series (0, 2, and 6 months). Currently, the CDC recommends that children aged under 15 years at the time of first dose may opt for a two-dose series (0 and 6-12 months). For those aged 15-26 years, the three-dose schedule remains the recommended course.

The benefits of two-dose schedule are convenience, cost, and increased likelihood of completion. Data presented at the 2017 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer showed that rates of cervical dysplasia were equivalent for women who completed a two-dose schedule versus a three-dose schedule.⁴

Efficacy

A recent meta-analysis of clinical trials of the HPV vaccines describe efficacy of 95%-97% in prevention of CIN 1-3.⁵ While its greatest efficacy is in its ability to prevent primary HPV infection, there still is some benefit for individuals who already were exposed to HPV prior to vaccination. As stated previously, women with a history of prior HPV vaccination have lower rates of recurrence of cervical dysplasia after treatment. Additionally, recent research has shown that women who received HPV vaccinations after a LEEP procedure for CIN 2 or 3 experience significantly lower recurrence rates, compared with women who did not receive vaccinations after LEEP (2.5% vs. 8.5%).⁶ This raises the possibility of a therapeutic role for HPV vaccination in women infected with HPV. Prospective studies are currently evaluating this question.

Myths

The most common side effects of the HPV vaccine are pain, redness, or swelling at the injection site. Other known side effects include fever, headache or malaise, nausea, syncope, or muscle/joint pain – similar to other vaccinations. Anaphylaxis is a rare complication.

Some parents and pediatricians report concerns that vaccination could lead to earlier sexual activity. Multiple studies have shown that girls who receive HPV vaccination are no more likely to become pregnant or get a sexually transmitted infection (proxies for intercourse) than are girls who were not vaccinated.^7,8

Maximizing vaccination rates