Human papillomavirus vaccine: Safe, effective, underused
ABSTRACTVaccination against human papillomavirus (HPV) is safe and effective. It is recommended for females age 9 to 26 and for males age 11 to 26, yet vaccination rates are low. We review the host immune response, the data behind the recommendations for HPV vaccination, and the challenges of implementing the vaccination program.
KEY POINTS
- Two HPV vaccines are available: a quadrivalent vaccine against HVP types 6, 11, 16, and 18, and a bivalent vaccine against types 16 and 18.
- HPV causes cervical cancer, genital warts, oropharyngeal cancer, anal cancer, and recurrent respiratory papillomatosis, creating a considerable economic and health burden.
- The host immune response to natural HPV infection is slow and weak. In contrast, HPV vaccine induces a strong and long-lasting immune response.
- The HPV vaccines have greater than 90% efficacy in preventing cervical dysplasia and genital warts that are caused by the HPV types the vaccine contains. They are as safe as other common prophylactic vaccines.
- HPV vaccination has been challenged by public controversy over the vaccine’s safety, teenage sexuality, mandatory legislation, and the cost of the vaccine.
FREQUENTLY ASKED QUESTIONS
What if the patient is late for a shot?
The current recommended vaccination schedule for the bivalent and quadrivalent HPV vaccines is a three-dose series administered at 0, 2, and 6 months, given as an intramuscular injection, preferably in the deltoid muscle. The minimal dosing interval is 4 weeks between the first and second doses and 12 weeks between the second and third doses.
The vaccines use different adjuncts with different specific mechanisms for immunogenicity; therefore, it is recommended that the same vaccine be used for the entire three-dose series. However, if circumstances preclude the completion of a series with the same vaccine, the other HPV vaccine may be used.63 Starting the series over is not recommended.
Long-term studies demonstrated clinical efficacy 8.5 years after vaccination.47 Amnestic response by virtue of activation of pools of memory B cells has been demonstrated, suggesting the vaccine may afford lifelong immunity.88
Is a pregnancy test needed before HPV vaccination?
The ACIP states that pregnancy testing is not required before receiving either of the available HPV vaccines.
A recent retrospective review of phase III efficacy trials and pregnancy registry surveillance data for both vaccines revealed no increase in spontaneous abortions, fetal malformations, or adverse pregnancy outcomes.89 Data are limited on bivalent and quadrivalent HPV vaccine given within 30 days of pregnancy and subsequent pregnancy and fetal outcomes. Both vaccines have been assigned a pregnancy rating of category B; however, the ACIP recommends that neither vaccine be given if the recipient is known to be pregnant. If pregnancy occurs, it is recommended that the remainder of the series be deferred until after delivery.62
It is not known whether the vaccine is excreted in breast milk. The manufacturers of both the bivalent and quadrivalent HPV vaccines recommend caution when vaccinating lactating women.30,31
Can HPV vaccine be given with other vaccines?
In randomized trials, giving the bivalent HPV vaccine with the combined hepatitis A, hepatitis B, meningococcal conjugate and the combined tetanus, diphtheria, and acellular pertussis vaccines did not interfere with the immunogenic response, was safe, and was well tolerated.90,91 Coadministration of the quadrivalent HPV vaccine has been studied only with hepatitis B vaccine, with similar safety and efficacy noted.
The ACIP recommends giving HPV vaccine at the same visit with other age-appropriate immunizations to increase the likelihood of adherence to recommended vaccination schedules.62
Is HPV vaccination cost-effective?
Kim and Goldie86 performed a cost-effectiveness analysis of HPV vaccination of girls at age 12 and catch-up vaccination up to the ages of 18, 21, and 26. For their analysis, they considered prevention of cancers associated with HPV types 16 and 18, of genital warts associated with types 6 and 11, and of recurrent respiratory papillomatosis. They also assumed that immunity would be lifelong, and current screening practices would continue.
They calculated that routine vaccination of 12-year-old girls resulted in an incremental cost-effective ratio of $34,900 per quality-adjusted life-year (QALY) gained. A threshold of less than $50,000 per QALY gained is considered reasonably cost-effective, with an upper limit of $100,000 considered acceptable.92
In the same analysis by Kim and Goldie,86 catch-up vaccination of girls through age 18 resulted in a cost of $50,000 to $100,000 per QALY gained, and catch-up vaccination of females through age 26 was significantly less cost-effective at more then $130,000 per QALY gained. The vaccine was also significantly less cost-effective if 5% of the population was neither screened nor vaccinated, if a 10-year booster was required, and if frequent cervical cancer screening intervals were adopted.
This analysis did not include costs related to the evaluation and treatment of abnormal Pap smears and cross-protection against other HPV-related cancers.
The cost-effectiveness of HPV vaccination depends on reaching more girls at younger ages (ideally before sexual debut) and completing the three-dose schedule to optimize duration of immunity.92 Appropriate modification of the current recommendations for the intervals of cervical cancer screening for vaccinated individuals will further improve the cost-effectiveness of vaccination. The inclusion of male vaccination generally has more favorable cost per QALY in scenarios in which female coverage rates are less than 50%93 and among men who have sex with men.94
TO ERADICATE CERVICAL CANCER
Given the remarkable efficacy and expected long-term immunogenicity of HPV vaccines, we anticipate a decline in HPV-related cervical cancer and other related diseases in the years to come. However, modeling studies predicting the impact of HPV vaccination suggest that although substantial reductions in diseases can be expected, the benefit, assuming high vaccination rates, will not be apparent for at least another decade.95 Furthermore, the current HPV vaccines contain only HPV 16 and 18 L1 protein for cancer protection and, therefore, do not provide optimal protection against all oncogenic HPV-related cancers.
The real hope of eradicating cervical cancer and all HPV-related disease relies on a successful global implementation of multivalent HPV vaccination, effective screening strategies, and successful treatment.
