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

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

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


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.


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

HPV vaccination rates in the United States lag significantly behind rates in countries with national vaccine programs, such as Australia and Denmark.9 Early data from Australia already have shown a decrease in genital warts and CIN 2+ incidence within the 10 years of starting its school-based vaccine program, with approximately 73% of 12- to 15-year-olds having completed the vaccine series.2 In contrast, just 40% and 22% of 13- to 17-year-old girls and boys in the United States, respectively, had completed the vaccine series in 2014, according to the CDC.10

Vaccination gaps between girls and boys are narrowing, and more teens will be able to complete the series with the new two-dose recommendation for those younger than 15 years. However, our current rates of vaccination are significantly lower for HPV than for other routinely recommended adolescent vaccines (such as Tdap and meningococcal) and more must be done to encourage vaccination.

Studies have shown that parents are more likely to vaccinate their children if providers recommend the vaccine.11 As women’s health care providers, we do not always see children during the time period that is ideal for vaccination. However, we take care of many women who are presenting for routine gynecologic care, pregnancy, or with abnormal Pap smear screenings. These are ideal opportunities to educate and offer HPV vaccination to women in the approved age groups, as well as to encourage parents to vaccinate their children.

As with other vaccines, the recommendation should be clear and focused on the cancer prevention benefit. Using methods in which the recommendation is “announced” in a brief statement assuming parents/patients are ready to vaccinate versus open-ended conversations, has been studied as a potentially successful method to increase uptake of HPV vaccination.12 Additionally, documentation of HPV vaccination status should be built into electronic medical record templates to prompt clinicians to ask and offer HPV vaccination at visits, including postpartum visits.

Cervical cancer, caused by HPV, is a preventable disease for which there is a highly effective vaccine. The challenge in the United States is adoption and completion of vaccination. The challenge in the developing world is one of access to the vaccine itself. It is important for ob.gyns. to arm themselves with strategies to identify and capture all individuals who might be eligible for vaccination and to educate them on this life-saving strategy.

Dr. Rahangdale is an associate professor of ob.gyn. at the University of North Carolina, Chapel Hill, and is director of the North Carolina Women’s Hospital Cervical Dysplasia Clinic. Dr. Rossi is an assistant professor in the division of gynecologic oncology at UNC-Chapel Hill. They reported having no relevant financial disclosures.


1. Am J Epidemiol. 2008 Jul 15;168(2):123-37.

2. Int J Cancer. 2012 Nov 1;131(9):1969-82.

3. BMJ. 2012 Mar 27;344:e1401. doi: 10.1136/bmj.e1401.

4. Gynecol Oncol. 2017 Jun. doi. org/10.1016/j.ygyno.2017.03.031.

5. Int J Prev Med. 2017 Jun 1;8:44. doi: 10.4103/ijpvm.IJPVM_413_16.

6. Gynecol Oncol. 2013 Aug;130(2):264-8.

7. Pediatrics. 2012 Nov;130(5):798-805.

8. JAMA Intern Med. 2015 Apr;175(4):617-23.

9. Clin Pediatr (Phila). 2016 Sep;55(10):904-14.

10. MMWR Morb Mortal Wkly Rep. 2015 Jul 31;64(29):784-92.

11. Vaccine. 2016 Feb 24;34(9):1187-92.

12. Pediatrics. 2017 Jan;139(1). pii:e20161764. doi: 10.1542/peds.2016-1764.


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