Human papillomavirus (HPV) is a virus from the papillomavirus family that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes, making it easily transmitted sexually or through other intimate contact. While the majority of the known types of HPV cause no symptoms in most people, some types can cause warts (verrucae). HPV types 16 and 18 cause approximately 70% of cervical cancers, and cause most HPV-induced anal, vulvar, vaginal, and penile cancers. The HPV quadrivalent vaccine, also known as Gardasil (or Silgard in Europe), is marketed by Merck. The vaccine prevents the transmission of certain types of HPV, specifically types 6, 11, 16 and 18.
Although the safety of HPV vaccine has been thoroughly vetted for safety in studies with large cohorts, the long time period (up to decades) from infection to a diagnosis of an HPV-related cancer has left questions about how to maximize effectiveness of the vaccine which required further research.
A recent study published in the Journal of the National Cancer Institute attempted to uncover what might be critical issues in improving the effectiveness of the vaccine to prevent genital warts (GW) and eventual cancers. The researchers looked at a group of females, ages 10-44 years, living in Sweden between 2006 and 2010. Out of that group, they examined GW incidence in relationship to HPV vaccination. Incidence rate (IR) ratios of genital warts were estimated using time-to-event analyses with adjustment for age and parental education level, stratified by age at first vaccination.
The key results in vaccine effectiveness (VE) were:
- VE was 76% among those who received three doses of the vaccine, with their first dose before 20 years of age.
- VE was highest, about 93%, in girls who were vaccinated before 14 years.
- VE was 80% for girls vaccinated at ages 14-16 years.
- VE was 71% for those vaccinated at ages 17-19 years.
- VE was 48% for women vaccinated at ages 20-22 years.
- Unfortunately, there was no measurable effectives in full vaccinated women who received their first dose after the age of 22.
For women over the age of 20, the rates of genital warts incidence decreased among the unvaccinated, which may suggest that women with a high risk of GW favorably used HPV vaccines. However, the authors noted that there were limitations to their data by stating that “interpreting the crude estimates of effectiveness for those aged 20 years or older at first vaccination is difficult because we found evidence suggesting a self-selection bias with women at high risk preferentially seeking vaccination.” Interestingly, the researchers found that girls who had at least one university educated parent were 15 times more likely to be vaccinated for HPV before age 20 years than females whose parents had not completed high school.
In an editorial that accompanied the article, the authors state that “future studies in Sweden—and elsewhere where HPV vaccine coverage rates are high in target populations, such as Australia and Canada—may need to compare vaccinated birth cohorts with older birth cohorts that were previously unvaccinated to evaluate the impact of vaccination on the population level.” The low HPV vaccination coverage prior to the establishment of the national school-based program in Sweden gave the opportunity to compare the incidence of genital warts in vaccinated cohorts with that in unvaccinated cohorts. And clearly the results show that the sooner girls get the vaccine, the higher the effectiveness.
“Young age at first vaccination is imperative for maximizing quadrivalent HPV vaccine effectiveness.”
- Klein NP, Hansen J, Chao C, Velicer C, Emery M, Slezak J, Lewis N, Deosaransingh K, Sy L, Ackerson B, Cheetham TC, Liaw KL, Takhar H, Jacobsen SJ. Safety of quadrivalent human papillomavirus vaccine administered routinely to females. Arch Pediatr Adolesc Med. 2012 Dec;166(12):1140-8. doi: 10.1001/archpediatrics.2012.1451. PubMed PMID: 23027469.
- Leval A, Herweijer E, Ploner A, Eloranta S, Fridman Simard J, Dillner J, Young C, Netterlid E, Sparén P, Arnheim-Dahlström L.Quadrivalent Human Papillomavirus Vaccine Effectiveness: A Swedish National Cohort Study. J Natl Cancer Inst. 2013 Mar 13. [Epub ahead of print] PubMed PMID: 23486550.
- Lowy DR, Schiller JT. Prophylactic human papillomavirus vaccines. J Clin Invest. 2006 May;116(5):1167-73. Review. PubMed PMID: 16670757; PubMed Central PMCID: PMC1451224.
- Markowitz LE, Dunne EF, Saraiya M, Lawson HW, Chesson H, Unger ER; Centers for Disease Control and Prevention (CDC); Advisory Committee on Immunization Practices (ACIP). Quadrivalent Human Papillomavirus Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007 Mar 23;56(RR-2):1-24. PubMed PMID: 17380109.
- Smith JS, Weiderpass E. Real world effectiveness of population-based roll out of human papillomavirus vaccination against rates of genital warts. J Natl Cancer Inst. 2013 March. DOI:10.1093/jnci/djt044. PubMed PMID: