by Dr. C.H. Weaver M.D. updated 7/2020
Since the approval of the first human papillomavirus (HPV) vaccine in 2006 doctors believed they were making steady progress toward the eradication of HPV caused cervical cancer and other HPV related diseases.
According to a 2019 study physician optimism may be premature. The results of a recent survey found that more than 70% of U.S. adults are unaware that the HPV causes anal, penile, and oral cancers. Two-thirds of men and one-third of women ages 18-26 did not know that HPV causes cervical cancer. Men are also less likely than women to know that the virus carries a risk of cancer.
To address these short comings the American Cancer Society (ACS) changed their recommendation for routine HPV vaccination to start at 9 years of age. According to the ACS, health care providers should begin offering routine HPV vaccination to both boys and girls as young as age 9 years in order to increase rates of on-time administration. Routinely vaccinating boys and girls between ages 9 and 12 years will likely lead to higher vaccination rates than routinely vaccinating between ages 11 and 12 years. In order to be maximally effective, HPV vaccination should occur before a child becomes sexually active and routine vaccination of boys is recommended. (6)
Regarding catch-up vaccination, the updated guideline endorses the ACIP’s recommendation to remove separate advice for males and females. It specifies that every individual who did not receive full HPV vaccination should have catch-up vaccinations up to age 26 years. The updated guideline also recommends against vaccination after age 26 years, because of its low effectiveness and poor potential to prevent cancer among these adults.
About Human Papilloma viruses
Human papillomaviruses have a wide range of health effects and vaccination programs initiated ~ 15 years ago offered hope for the prevention and perhaps even lead the eradication of HPV related diseases. Currently available vaccines have the potential to prevent an estimated 70 percent of all cervical cancers. The story of HPV does not end there, however. Work continues to understand the full range of HPV’s effects; in addition to contributing to cervical cancer, high-risk types of HPV have been linked with cancers of the vulva, vagina, penis, anus, and some cancers of the head and neck. Researchers also continue to monitor HPV vaccine safety and have extended vaccine recommendations to additional segments of the population, such as boys. The ultimate goal is the eradication of cancers that claim more than 300,000 lives worldwide each year and to reduce the occurrence of other HPV related diseases.
Human papillomaviruses consist of more than 100 different types. Some types of HPV cause warts on the hands or feet; others cause genital warts; and some have been linked with cancer, most notably cervical cancer. The types of HPV that are linked with cervical cancer and genital warts are transmitted sexually. Genital HPV infection is extremely common and generally occurs soon after an individual becomes sexually active. The likelihood that an HPV infection will develop into cancer depends in part on the HPV type and the persistence of the infection. Certain types of HPV have been more strongly linked with cancer than others and are referred to as “high-risk.” HPV types 16 and 18, for example, are high-risk types that are thought to account for roughly 70 percent of all cases of cervical cancer. Among women infected with a high-risk type of HPV, persistent infection is the major risk factor for cervical cancer.Infection with a high-risk type of HPV does not necessarily lead to cancer. Many infections disappear on their own, (2) and others may persist without causing cancer. Infection with a high-risk type of HPV does, however, increase the risk of cancer, and virtually all cases of cervical cancer can be linked to infection with a high-risk type of HPV. Among women infected with HPV, smoking appears to significantly increase the risk of cervical abnormalities, (3) providing yet another reason for women to avoid tobacco.
Gardasil® and Cervarix,® are commercially available HPV vaccines intended to prevent infection with certain types of HPV; these vaccines do not treat existing HPV infections or cervical abnormalities. It’s also important to keep in mind that these vaccines do not protect against all types of HPV; women who are vaccinated should continue to be screened for cervical cancer.
Gardasil protects against HPV types 6 and 11 (which are linked to genital warts) as well as the cancer-associated types 16 and 18. The vaccine was approved in 2006 for use in girls and women between the ages of 9 and 26 years. Because the vaccine is not effective against existing infections, it is likely to have the greatest effect when given before a girl becomes sexually active. The Advisory Committee on Immunization Practices at the U.S. Centers for Disease Control and Prevention (CDC) recommends routine vaccination of girls 11 to 12 years of age.(3)Since its licensure Gardasil has been featured prominently in the media, as scientists, healthcare providers, policy makers, and parents have discussed issues of the effectiveness, safety, and scope of vaccine recommendations. According to John Iskander, MD, MPH, associate director for science in the Immunization Safety Office of the CDC, such attention was not unexpected: “This vaccine was not only new but novel. It was targeting a sexually transmitted disease; it was targeting adolescents, who are not traditionally a major target for vaccines; and it was targeting cancer prevention. When you look at all of those factors together, it’s not surprising that it’s drawn this degree of interest.”
What vaccines are available?
There are currently two FDA-approved vaccines that protect against the types of HPV associated with cervical cancer.
- Gardasil® (quadrivalent human papillomavirus [types 6, 11, 16, 18] recombinant vaccine), which prevents infection with four types of HPV—types 6, 11, 16, and 18.
- Cervarix® (human papillomavirus bivalent [types 16 and 18] recombinant vaccine) , which targets HPV types 16 and 18. HPV types 16 and 18 cause roughly 70% of all cases of cervical cancer, and HPV types 6 and 11 account for roughly 90% of genital warts.
Gardasil® also Likely to Prevent Most Vaginal and Vulvar Cancers
According to results presented at the annual meeting of the American Society of Clinical Oncology, Gardasil® also reduces the risk of high-grade precancerous changes to the vulva and vagina. The analysis combined information from three randomized clinical trials conducted in the U.S., Europe, South America, and Asia. The trials enrolled a total of 18,150 women between the ages of 16 and 26. Study participants were randomly assigned to receive three doses of Gardasil or a placebo. Participants were followed for an average of two years.
- There were no cases of HPV16- or HPV18-related vaginal or vulvar pre cancers among women who received Gardasil.
- Among women who received a placebo, there were 24 cases of HPV16- or HPV18-related vaginal or vulvar pre cancers.
The researchers concluded that Gardasil is highly effective in protecting against HPV16- and HPV18-related vaginal and vulvar precancers. The vaccine is expected to reduce the occurrence of vulvar and vaginal cancer in addition to reducing the occurrence of cervical cancer.
Cervarix® Effective Against Cervical Precancers
A vaccine against two high-risk types of HPV reduced the risk of precancerous cervical changes in young women. These results were published in The Lancet.
The PATRICIA trial (PApilloma TRIal against Cancer In young Adults) is a Phase III clinical trial that evaluated the efficacy of Cervarix against precancerous changes to the cervix (cervical intraepithelial neoplasia 2 or worse). The study enrolled more than 18,000 women between the ages of 15 and 25 years. Roughly half of the women were assigned to receive Cervarix. The vaccine was given in three doses over a six-month period.
Study participants have now been followed for an average of almost three years.
Vaccine efficacy against precancerous cervical changes due to HPV16 or HPV18 was 93%. Vaccine efficacy against precancerous cervical changes due to 12 other high-risk types of HPV (HPV types not included in the vaccine) was estimated to be between 37% and 54%. This was mainly the result of cross-protection against HPV31, HPV33, and HPV45. This study suggests that Cervarix is highly effective at preventing HPV16- and HPV18-related precancerous cervical changes. Cervarix also appears to offer some degree of cross-protection against three other high-risk types of HPV.(9)
Vaccination Remains Effective for Greater Than Six Years
Cervarix®—a vaccine that reduces the risk of cervical cancer by protecting against two high-risk types of human papillomavirus (HPV)—remains effective for more than six years. These results were published in the Lancet. In order to have the greatest impact, these vaccines will need to provide sustained protection against HPV infection. To evaluate the efficacy of Cervarix up to 6.4 years after vaccination, researchers evaluated information from studies conducted in girls and women between the ages of 15 and 25 years.
- Vaccine efficacy against infection with HPV16 or 18 was 95.3%.
- Vaccine efficacy against precancerous or cancerous changes to the cervix (cervical intraepithelial neoplasia 2+) linked with HPV16 or 18 was 100%.
- Vaccine efficacy against all precancerous or cancerous changes to the cervix (regardless of HPV type) was 71.9%.
These results indicate that Cervarix protects against HPV16/18 infections and precancerous or cancerous changes to the cervix for more than six years. (8)
Women Over 40 Don't Benefit From Vaccination
Women over the age of 40 are not likely to benefit from a vaccine designed to prevent HPV, according to the results of a study published in the Journal of the National Cancer Institute.(7)
Currently, there are two vaccines approved for the prevention of HPV; Gardasil® and Cervarix®. study of more than 9,000 Costa Rican women ages 19 to 97 evaluated the patterns of HPV infection as women age. The researchers found that the rate of newly detected infections declined with age—from 35% in women ages 18-25 to 13.5% in women over the age of 42. In both younger and older women, new infections typically cleared up without treatment within two years. They found that new infections typically did not progress to worse disease in older women.
Based on their findings, the researchers concluded that HPV vaccination was not likely to be beneficial for older women. The vaccinations are used to prevent new infections, and older women are not getting many new infections.
- Saslow D, Andrews KS, Manassaram-Baptiste D, et al. Human papillomavirus vaccination 2020 guideline update: American Cancer Society guideline adaptation. Published online July 8, 2020. CA-Cancer J Clin. Doi:10.3322/caac.21616
- Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. New EnglandJournal of Medicine. 1998;338(7):423-28.
- Wang SS, Zuna RE, Wentzensen N, et al. Human papillomavirus cofactors by disease progression and human papillomavirus types in the Study to Understand Cervical Cancer Early Endpoints and Determinants. Cancer Epidemiology, Biomarkers, and Prevention. 2009;18(1):113-20.
- Skjeldestad FE. Prophylactic quadrivalent human papillomavirus (HPV) (Types 6, 11, 16, 18) L1 virus-like particle (VLP) vaccine (Gardasil™) reduces cervical intraepithelial neoplasia (CIN) 2/3 risk. Abstract LB-8a. Presented at the 2005 meeting of the Infectious Diseases Society of America.
- Paavonen J, for the FUTURE II Study Group. Efficacy of a Quadrivalent HPV (Types 6/11/16/18) Virus-like Particle (VLP) Against Vaginal and Vulvar Pre-Cancerous Lesions: A Combined Analysis. Presented at the 2006 ASCO Annual Meeting. Abstract #5011.
- American Academy of Pediatrics, Committee on Infectious Diseases. Policy Statement: Recommended Childhood and Adolescent Immunization Schedules—United States, 2012. Pediatrics. 2012;129:385-386.
- Rodriguez AC, Schiffman M, Herrero R, et al. Longitudinal study of human papillomavirus persistence and cervical intraepithelial neoplasia grade 2/3: Critical role of duration of infection. Journal of the National Cancer Institute. 2010; 102: 315-324.
- Paavonen J, Naud P, Salmeron J et al. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomized study in young women. Lancet [early online publication]. July 7, 2009.
- The GlaxoSmithKline Vaccine HPV-007 Study Group. Sustained efficacy and immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine: analysis of a randomised placebo-controlled trial up to 6.4 years. Lancet. 2009;274:1975-85.