Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide. It affects 80% of individuals, with the initial infection usually occurring between the ages of 15 and 24. Persistent infection with oncogenic HPV genotypes, primarily 16 and 18, is the cause of virtually all cervical and anal cancers, as well as a majority of oropharyngeal, vaginal, vulvar, and penile cancers.1,2 Cervical cancer is the fourth most common cancer in women worldwide, the second or third most common cancer in most low- and middle-income countries, and the leading cancer of sub-Saharan Africa.3
Women are suffering needlessly and dying prematurely from a disease that can be prevented through screening and early detection. Such programs have proven to be widely successful in affluent countries, but they have not been implemented or fully realized in most low- and middle-income countries and in some underserved populations of affluent countries. Without effective prevention and treatment programs, by 2035 cervical cancer deaths are expected to exceed 400,000 worldwide, with over 95% occurring in low- and middle-income countries.4
Epidemic of Oropharyngeal Cancers in Men
Prophylactic HPV vaccines have been available since 2006 and are very effective if given prior to initiation of sexual activity and exposure to HPV.5-7 However, control of cervical cancer in high-income countries had been mostly achieved prior to 2006, owing to significant investments in screening and treatment of premalignant cervical disease (approximately $6.5 billion annually in the United States). For low- and middle-income countries, prophylactic vaccination would be the easiest and most efficient means toward future cervical cancer control and ultimately saving millions of women’s lives.
Recent reports from other countries provide strong evidence that HPV-related disease in the United States will be controlled if HPV vaccination is embraced.— Erich M. Sturgis, MD, MPH
Men, on the other hand, are experiencing an epidemic of oropharyngeal cancers in most affluent regions of the world. In the United States, for instance, the annual incidence of oropharyngeal cancer (tonsils and base of the tongue/lingual tonsil) now outnumbers that of cervical cancer in women, and, among white men it is rising at 10% each year.2,8 Unlike cervical cancer, there is no screening test available for oropharyngeal cancer, and, regrettably, the disease is almost always detected at an advanced stage.
Similarly, the incidence of anal cancer in the United States is increasing significantly in both men and women—approximately 3% per year—and among white women 4% and among black men 6%.1 Screening is not widely available or practiced due to the rarity of the disease and a lack of evidence-based screening guidelines for high-risk groups, such as those with HIV, men who have sex with men, and women with prior cervical cancer or high-grade dysplasia. With broader implementation of HPV testing in women, it is possible that a larger at-risk population will be revealed.
The incidence of vulvar cancer also appears to be significantly increasing and with vaginal cancer accounts for more than 4,000 new cases per year in the United States.1,2 Penile cancer, although rare in developed countries, accounts for up to 10% of cancers in men in some registries in low- and middle-income countries.9 Given that screening is currently unavailable, optimizing HPV vaccination rates in children, adolescents, and young adults is the only currently available cancer prevention option for HPV-related cancers at noncervical sites.
Overcoming Low Vaccination Rates, Especially in Boys
Although proven efficacious and safe, the uptake of HPV vaccines has been variable. In the United States, only 42% of adolescent girls and 28% of boys have completed the vaccination series. Vaccination is not recommended for boys in some countries, and many low- and middle-income countries do not have any HPV vaccination programs. Reasons for low vaccination rates in the United States include inadequate provider recommendations, parent opposition, few state-level mandates requiring HPV vaccination for school enrollment, lack of school-based immunization programs, and misinformation about safety propagated through social media. Greater suffering, loss of life, and increased financial burden will result from further delays in expanding HPV vaccination programs or allowing vaccination rates to lag in boys.
The human burden from HPV-related cancers can be reduced and eventually eliminated. Widescale implementation of vaccination programs, together with effective screening and early detection for individuals in the gap generations, is the key to eradicating HPV-related cancers.— Erich M. Sturgis, MD, MPH
Recent reports from other countries provide strong evidence that HPV-related disease in the United States will be controlled if HPV vaccination is embraced. For instance, Australia implemented a national vaccine program in 2007 for adolescent girls and achieved over 70% coverage by 2011. Australian national surveillance data demonstrate a precipitous drop in the diagnosis of genital warts from 12% in adolescent females in 2007 to less than 1% in 2011. Although the vaccination program was not extended to include boys until 2012, there was an indirect effect of universal immunization of girls, with an 82% decline in diagnoses of genital warts among heterosexual adolescent boys.10
Achieving high rates of vaccination is not restricted to affluent countries. In 2011, Rwanda launched an aggressive HPV immunization program in concert with Merck, which provided 2 million vaccine doses to girls between the ages of 9 and 14. As of 2013, full-course coverage had reached 99%.11 Although the Merck program ended in 2013, immunization will continue through at least 2017 due to funding from the Global Alliance for Vaccines and Immunization, launched in 2000 by the Bill and Melinda Gates Foundation. Vaccine costs per child are $2.60, with co-financing from Rwanda at $0.20 per child.
Similarly, Panama has recognized the opportunity of HPV vaccination and since 2008 has allocated $5 million annually for mandatory, no-cost vaccination for girls 10 years of age, in schools and health clinics. Panama was the first Latin American country to require HPV vaccinations, and, within 2 years of the program’s inception, 67% of age-eligible girls were fully vaccinated.12 Clearly, we in the United States have work to do.
Universal Implementation of HPV Vaccination
In 2016, all 69 National Cancer Institute–designated cancer centers signed a consensus statement strongly endorsing HPV vaccination as safe and effective for both girls and boys and critical to our nation’s cancer prevention strategy.13 Recently, the NCI-designated cancer centers universally endorsed a second consensus statement supporting the new 2-dose vaccination regimen for boys and girls under age 15, with a 3-dose catch-up vaccination regimen for those 15 to 26 years old and calling for all health-care providers to be strong advocates for HPV vaccination.14
Here at MD Anderson Cancer Center, we echo these consensus statements and call for providers to universally implement HPV vaccination, advocate for policies supporting HPV vaccination, educate the uninformed, speak out against the propagation of misinformation, and fight attempts to legitimize antivaccine leaders who advocate non–science-based claims. Globally, we encourage individual countries to include HPV vaccination as part of basic cancer prevention efforts similar to those seen with tobacco and alcohol control, sun and ultraviolet protection, viral hepatitis screening and vaccination, and healthy diet/lifestyle support, and we advocate for universal inclusion of boys in HPV vaccination programs for countries with existing or emerging epidemics of HPV-related cancers in men. We believe it is imperative that industry and nongovernmental organizations work to support the implementation of HPV vaccination programs in low- and middle-income countries.
Moreover, screening and early detection for the tens of millions already infected with HPV must be given attention. Even if we could achieve overnight universal vaccination of adolescents, approximately 1 in 4 individuals, or 80 million people, in the United States alone is currently HPV-infected, and most adults who have not been vaccinated have had an HPV infection at some point. Given that current prophylactic vaccines have no effect on preexisting HPV infections and related dysplasias or cancers, millions of individuals are in the “gap generations”—those not vaccinated before HPV exposure.
Additionally, because screening is not available or feasible for virtually all noncervical HPV-associated cancers, we will likely continue to experience an increasing burden of HPV-associated cancers, particularly in men. As a result, the global cervical cancer burden is not expected to decrease until after 2050, and the oropharyngeal cancer burden will likely not decrease until after 2060 without effective screening and early detection.15
Hurdles of Oropharyngeal Cancer Screening
With adequate and standard screening, most cervical cancers can be prevented for the gap generations, and screening for anal cancer may be possible for high-risk groups; however, oropharyngeal cancer screening does not appear possible for the foreseeable future. Two key hurdles must be overcome to realize oropharyngeal cancer screening: first, the current lack of a proven method to identify a high-risk group; and second, the technical challenges with detecting precancerous lesions and early invasive cancers in a mucosal field notoriously difficult to examine.
To address these issues, we have instituted a clinical trial for HPV screening of men between the ages of 55 and 59 years in Southeast Texas: HPV-Related Oropharyngeal and Uncommon Cancers Screening Trial of Men (“HOUSTON” ClinicalTrials.gov identifier NCT02897427).
Eliminating HPV-Related Cancers
The human burden from HPV-related cancers can be reduced and eventually eliminated. Widescale implementation of vaccination programs, together with effective screening and early detection for individuals in the gap generations, is the key to eradicating HPV-related cancers.
For more information on HPV vaccination, as well as HPV-related cancer screenings and treatment, see the websites listed in the sidebar on page 96.
This column was written in partnership with my colleagues at The University of Texas MD Anderson Cancer Center: Cathy Eng, MD, Professor in the Department of Gastrointestinal Medical Oncology; Curtis A. Pettaway, MD, Professor in the Department of Urology; Lois M. Ramondetta, MD, Professor in the Department of Gynecologic Oncology and Reproductive Medicine; and Kathleen M. Schmeler, MD, Associate Professor in the Department of Gynecologic Oncology and Reproductive Medicine. I also would like to acknowledge Sherri Patterson for her contribution in the preparation of this column. ■
Dr. Sturgis is Professor in the Department of Head and Neck Surgery and in the Department of Epidemiology; the Christopher and Susan Damico Chair in Viral Associated Malignancies; Program Director of the Oropharynx Program; and Administrative Leader of the HPV-related Cancers Moon Shot at The University of Texas MD Anderson Cancer Center in Houston.
Disclaimer: This commentary represents the views of the author and may not necessarily reflect the views of ASCO.
1. Jemal A, Simard EP, Dorell C, et al: Annual Report to the Nation on the Status of Cancer, 1975-2009, featuring the burden and trends in human papillomavirus (HPV)-associated cancers and HPV vaccination coverage levels. J Natl Cancer Inst 105:175-201, 2013.
3. GLOBOCAN Cancer Fact Sheets: Cervical Cancer, Estimated Incidence, Mortality, and Prevalence Worldwide in 2012. Available at http://globocan.iarc.fr/old/FactSheets/cancers/cervix-new.asp. Accessed February 21, 2017.
4. The Global Alliance for Vaccines and Immunization (GAVI). Available at http://www.gavi.org/library/news/press-releases/2014/1-5-million-girls-set-to-benefit-from-vaccine-against-cervical-cancer/. Accessed February 21, 2017.
6. Paavonen J, Naud P, Salmerón 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, randomised study in young women. Lancet 374:301-314, 2009.
11. Bruni L, Barrionuevo-Rosas L, Albero G, et al: ICO Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in Rwanda. December 2016. Available at http://www.hpvcentre.net/statistics/reports/RWA.pdf. Accessed February 21, 2017.
12. Bruni L, Barrionuevo-Rosas L, Albero G, et al: ICO Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in Panama. December 2016. Available at http://www.hpvcentre.net/statistics/reports/PAN.pdf. Accessed February 21, 2017.
13. American Pharmacists Association: NCI-designated Cancer Centers Endorse Update HPV Vaccination Recommendations. Available at https://www.pharmacist.com/article/nci-designated-cancer-centers-endorse-updated-hpv-vaccination-recommendations. Accessed February 21, 2017.
14. NCI-Designated Cancer Centers Endorse Updated HPV Vaccination Recommendations: Available at http://cancer.ucsf.edu/_docs/HPVConsensusStatement_Jan2017.pdf. Accessed February 21, 2017.
Sources of Information on HPV Vaccination
American Cancer Society
Centers for Disease Control and Prevention
MD Anderson HPV-Related Cancers Moon Shots
National Cancer Institute
Prevent Cancer Foundation, Think About The Link
The Immunization Partnership