Cervical cancer may be the first human cancer to have a single identifiable cause: high-risk human papillomaviruses (HPVs). Evidence of these oncogenic HPV infections has been noted in virtually all (99.7%) cervical cancers. This is a unique association found in cancer research. Even tobacco use does not have the impact on lung cancer that HPV has on cervical cancer. Smokers have a tenfold risk of lung cancer and, when evaluated with a 40% prevalence rate of smoking, it is found that 80% of lung cancers are attributable to smoking. The 100-fold increased risk of cervical cancer found with HPV when evaluated with a prevalence of 80%, reveals that over 95% of cervical cancers are due to HPV Citation[1]. Furthermore, high-risk HPV also accounts for 50% of vaginal, vulvar and penile cancers and up to 70% of anal cancers.
Although there are over 100 different types of HPV, types 16 and 18 account for 70% of cervical cancer Citation[2]. HPV types 6 and 11 alone account for approximately 10% of cervical intraepithelial neoplasia (CIN) 1 and, when types 16 and 18 are also considered, this rises to 35–50%. HPV types 6 and 11 also account for 90% of genital warts Citation[3,4].
The new quadrivalent HPV-6, -11, -16, -18 vaccine (Gardasil®, Merck & Co., Inc., NJ, USA) is reported to demonstrate 100% protection against persistent HPV-16/18 and HPV-16/18-related CIN 2 and 3. Among 8487 women vaccinated in the Per Protocol group, there were no CIN 2/3 cases, in contrast to 53 cases in the 8460 women who received the placebo. Furthermore, the vaccine is still 97% effective in preventing HPV-16/18-positive CIN 2/3 even when administered to individuals who were already positive for one or more HPV types or who had serological evidence of prior type-specific infection or received fewer than the three recommended doses of vaccine. Gardasil is similarly protective for HPV-6 or -11 genital warts Citation[5,6].
The bivalent HPV-16/18 vaccine has similarly been noted to be 94% effective in preventing 12-month persistent HPV-16 or -18 infection of the cervix and 96% effective in preventing HPV-16/18-associated abnormal cytology. In addition, the bivalent vaccine has shown 100% efficacy against CIN due to HPV-16 or -18. Both of these vaccines are highly immunogenic and well tolerated Citation[7].
This incredible advance was addressed this year in a consensus statement published in the Pediatrics Infectious Disease JournalCitation[8] and in a recent review Citation[7] and bears summarizing:
| • | Cervical cancer is a preventable disease; | ||||
| • | HPV is a significant cause of cervical cancer and is a major healthcare burden; | ||||
| • | The incidence of genital HPV infections and HPV-associated clinical disease is greatest in men and women who have become sexually active recently; | ||||
| • | Most sexually active men and women will acquire genital HPV infection; | ||||
| • | The risk of HPV infection increases substantially with each new partner; | ||||
| • | Condom use decreases the risk of HPV transmission but is not fully protective; | ||||
| • | HPV vaccinations are a safe and efficacious method of preventing genital HPV infection and cervical cancer and are the primary prevention method for cervical cancer; | ||||
| • | Healthcare providers will be responsible for fostering HPV vaccine acceptance among parents and adolescents; | ||||
| • | Preventing HPV infection in both men and women would be expected to reduce HPV-associated morbidity and mortality in both sexes. | ||||
HPV vaccination could be the next major public-health breakthrough, with the potential to prevent the millions of deaths due to cervical cancer and other HPV-related diseases worldwide Citation[9]. To be successful, we will need to expand our knowledge concerning the effectiveness of the vaccine across a wide range of conditions. There is a need to determine the duration of protection, the extent of any crossover viral protection among viral types, the efficacy in HIV and in other immunocompromised individuals, the efficacy in males and also in blocking sexual transmission.
HPV vaccination is a cost-effective public-health measure for disease prevention that will have its maximum impact in developing countries with high cervical cancer rates. Fortunately, the worldwide experience with hepatitis B vaccination serves as a model for anticipating problems in delivery. However, there is a need for surveys to determine and improve vaccine acceptability in culturally diverse settings. The high production costs, need for cold transport and three intramuscular injections for HPV vaccine may be difficulties for developing countries and research to develop a less costly, non-temperature-sensitive vaccine with single dose efficacy will play a significant role in implementation worldwide. Hopefully, the experience of the Global Alliance for Vaccines and Immunization (GAVI) and the WHO may provide insights into innovative funding mechanisms to guarantee long-term availability of vaccines at low cost for developing countries.
In the meantime, we, as individual healthcare providers, can influence the areas in which we practice by educating others regarding HPV and its link to clinical disease and cancer, encouraging vaccination and, thereby, in the words of Franco and coworkers, ‘make the new model of cervical cancer through vaccination one of the most successful stories in modern preventative medicine’ Citation[10].
Disclosure
| • | Barr Pharmaceuticals/Duramed – research | ||||
| • | GlaxoSmithKline: Advisory Board – Consultant | ||||
| • | Merck Pharmaceuticals: Advisory Board – Consultant Speakers Bureau | ||||
| • | Pfizer – research | ||||
References
- Franco EL, Harper DM. Vaccination against human papillomavirus infection: a new paradigm in cervical cancer control. Vaccine23, 2388–2394 (2005).
- Munoz N, Bosch FX, De Sanjose S et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N. Engl. J. Med.348(6), 518–527 (2003).
- Greer CE, Wheeler CM, Ladner MB et al. Human papillomavirus (HPV) type distribution and serologic response to HPV type 6 virus-like particles in patients with genital warts. J. Clin. Microbiol.33(8), 2058–2063 (1995).
- Li HX, Zhu WY, Xia MY. Detection with the polymerase chain reaction of human papillomavirus DNA in condyloma acuminata treated with CO2 laser and microwave. Int. J. Dermatol.34(3), 209–211 (1995).
- Skjeldstad FE, Koutsky LA, for the Merck Phase 3 HPV Vaccine Steering Committee (Future III). Phase II trial of prophylactic quadrivalent HPV 6, 11, 16, 18 L1 virus-like particle (VLP) vaccine: prevention of cervical intraepithelial neoplasia (CIN)2/3 including adeno- and squamous cell carcinoma in situ (CIS). Presented at: Infectious Diseases Society of America. Late Breaker Session 66, LB-8A. San Francisco, CA, USA, October 7, 2005.
- Munoz N. A review of the Phase III clinical data for the quadrivalent human papilloma virus vaccine (Gardasil®). Europ. J. Obstet. Gyn. Rep. Biol. doi:10.1016/j.ejogrb.2006.06.024. (2006).
- Koutsky LA, Harper DM. Chapter 13. Current findings from prophylactic HPV trials. Vaccine24(Suppl. 3), S114–S121 (2006).
- Frazer IH, Cox JT, Mayeaux EJ et al. Advances in prevention of cervical cancer and other human papillomavirus-related diseases. Pediatr. Infect. Dis. J.25(Suppl.), S65–S81 (2006).
- Lentinen M, Herrero R, Mayaud P et al. Chapter 28. Studies to assess the long-term efficacy and effectiveness of HPV vaccination in developed and developing countries. Vaccine24(Suppl. 3), S233–S241 (2006).
- Franco EL, Bosch FX, Cuzick J et al. Chapter 29. Knowledge gaps and priorities for research of HPV infection and cervical cancer. Vaccine24(Suppl. 3), S242–S249 (2006).