To achieve its goal of eliminating cervical cancer, the World Health Organization (WHO) is calling on all countries “to reach and maintain an incidence rate of below 4 per 100,000 women.” Doing so would depend on the following:
- A total of 90% of girls being fully vaccinated against human papillomavirus (HPV) by age 15
- A total of 70% of women screened for cervical cancer by age 35 and again by age 45
- Treatment and management of 90% of women who have a precancerous lesion and 90% of women with invasive cancer.
This is an ambitious strategy, as WHO had acknowledged,1 but Ruanne Barnabas, MBChB, MSc, DPhil, MD, PhD, told The ASCO Post that it can be done. “We have the technology and the tools,” she said. The key to hitting those targets is to work “in partnership with communities and people to prevent these deaths of women.” Dr. Barnabas is Chief of the Division of Infectious Diseases at Massachusetts General Hospital, Boston, and a faculty member at Harvard Medical School.
Ruanne Barnabas, MBChB, MSc, DPhil, MD, PhD
Most cases of cervical cancer are caused by HPV infection, particularly HPV types 16 and 18 (HPV-16/18), although not all women who have an HPV infection will develop cervical cancer. The commonly used four-valent vaccine has been shown to be effective against HPV-16/18.
Countries Leading in HPV Vaccination
“In countries where HPV vaccination coverage is very high, and access to cervical cancer screening is also high,” estimates already exist for the elimination of cervical cancer, Dr. Barnabas noted. “In Australia, for example, 2024 is the target date to eliminate cervical cancer as a public health problem.”
Rwanda could become “the first country in Africa, and possibly the world, to eliminate cervical cancer,” even before Australia, according to an article in The Guardian.2 The article credits the deployment of “tens of thousands of community health workers to raise awareness of the disease,” along with “rapidly expanding cervical cancer testing” and a successful vaccination program for 12-year-old girls.
HPV Vaccination in the United States
In the United States, “we are not too far behind” in reaching the goal of eliminating cervical cancer, Dr. Barnabas said, but there are still barriers to overcome.
“We can do HPV vaccination. We have excellent screening and treatment,” Dr. Barnabas acknowledged. “But, in the United States, it will be access that proves to be one of the main barriers. Is everyone who needs a vaccine getting it? Are people who need screening accessing screening on time? Do they have health insurance? Can they afford the copay from the treatment? There is no doubt that technologically, we are well positioned, but are we reaching people?”
Cases of cervical cancer are decreasing among people who are screened frequently, but these women “are often in the lowest-risk category because they have had access to health insurance and have been vaccinated,” Dr. Barnabas pointed out. “It is those people who have never been vaccinated, who have never been screened, who are at the highest risk, and I worry that if we can’t increase access in the United States, we will still be stuck at a higher level of the number of cases of new cancers. And then, because it is diagnosed so late, the mortality can be higher.”
“We can do HPV vaccination. But, in the United States, it will be access that proves to be one of the main barriers.”— Ruanne Barnabas, MBChB, MSc, DPhil, MD, PhD
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“Steady improvements in HPV vaccination coverage during the past decade may have translated into protective benefits” among U.S. women born in the 1990s, according to a study reported in JAMA Health Forum.3 “You can absolutely see the steady improvement and overall, the number of people who have received at least one dose of the vaccine is high.” Dr. Barnabas commented. “We know the benefits are high. We have seen year-over-year improvements.”
The researchers analyzed data for 2,698 women who were in the 18- to 26-year-old group in one of two cycles of the National Health and Nutritional Examination Survey, either in 2005 to 2006, when HPV vaccination was first recommended for routine use, or 10 years later, from 2015 and 2016. Before the vaccine was introduced, the prevalence of HPV-16/18 was 15.2% in these women, whereas more recently, the prevalence was 3.3% overall, 5.1% among the unvaccinated, and 1.0% among the vaccinated.
Change in Age Distribution
“This study provides a birth cohort perspective and suggests a change in the age distribution of HPV-16/18 prevalence,” the authors noted.
“The point the authors raised about the age at which we can expect to see the most HPV cases as having changed from women in their 20s to above the age of 30 is really a big difference from what we have seen previously in the prevaccination era,” Dr. Barnabas stated. Although guidelines call for routine vaccination before women are in their 30s, HPV vaccination can also offer protection for older women who do not already have HPV infection.
“If you don’t have HPV at the time of vaccination, the vaccination works,” Dr. Barnabas stressed. “It doesn’t matter what has happened in the past; you can even be receiving treatment for dysplastic lesions. If you don’t have HPV at the time of vaccination, the vaccination will prevent you from getting new infections.”
Herd Immunity
“A larger decline in the prevalence of HPV-16/18 infection among 18- to 20-year-old women from 2015 to 2016 may reflect greater direct and herd protection from broader HPV vaccination coverage,” the authors wrote.
Dr. Barnabas agreed. “Countries where vaccination coverage is high see almost double the benefits of
vaccinations,” she stated. “They see the benefits among people who are not vaccinated as well as those who are. So, it is clear there are herd immunity benefits from HPV vaccination. If you can bring down the risk that anyone you come into contact with is infected with HPV, there are benefits to you as well.”
The WHO target of a 90% HPV vaccination rate is linked to herd immunity. “When you vaccinate 90% of people, everyone else will benefit from herd immunity,” Dr. Barnabas explained.
One Dose or Two?
A study assessed the efficacy of the single-dose HPV vaccine among 2,275 Kenyan women between the ages of 15 and 20.4 The investigators found that “the single dose worked as well as two or three doses,” reported Dr. Barnabas, the study’s principal investigator. “Over the 18-month period we studied, single-dose bivalent and nonvalent HPV vaccines were each highly effective in preventing incident persistent oncogenic HPV infection, similar to multidose regimens,” Dr. Barnabas and coauthors reported. “We are continuing to show the durability of the effects,” she added.
“We hope this is a game-changer for access to vaccines,” simplifying the vaccination process and reducing costs, Dr. Barnabas explained. “Given the efficacy is the same, WHO has recommended either one or two doses of the HPV vaccine for ages 9 to 20.”
What About Boys and Young Men?
The current recommendations from the Centers for Disease Control and Prevention (CDC) call for boys and young men also to be vaccinated against HPV infections.
“HPV is associated with anogenital cancers among men and women. HPV vaccination can prevent anogenital cancers, penile cancers, and other types of cancer. Unlike cervical cancer, where just about 100% of cervical cancers are attributable to HPV, the anogenital cancers vary between 50% and 90%,” Dr. Barnabas explained.
“Oropharyngeal cancers in men and women also can be prevented by HPV vaccination,” she continued. “We underestimate the impact of HPV vaccination when we focus on cervical cancer. It definitely has other benefits.”
Vaccination at Surgery
A meta-analysis of observational studies and randomized controlled trials suggested that adjuvant HPV vaccination at the time of local excision for cervical intraepithelial neoplasia (CIN) “might lead to a reduction in the risk of recurrence of high-grade preinvasive disease (CIN2+). The effect estimate was even more pronounced for CIN2+ related to HPV-16 or HPV-18,” researchers reported in BMJ.5
The study “raises the possibility that even if you have had HPV in the past, there could still be some benefit to vaccination,” Dr. Barnabas said. “The findings from the study, even though it was a meta-analysis, are quite compelling, and they do deserve some further work. It makes sense that if you have encountered HPV in the past, you could encounter it again, and if you don’t have it, you can benefit from vaccination.”
New Screening Technologies
Access to cervical cancer screening remains a “key component of the equation for us to fix. Screening and early detection make it much easier to prevent progression of dysplastic lesions to cancer,” Dr. Barnabas stated.
Specifically, access to screening needs to be increased among uninsured women, women who are immigrants, or undocumented people; they may not be able to get time off from work to go to screenings, she mentioned. Also, women who live in areas without good access to medical care in general, such as more rural areas, may have difficulty accessing HPV screening as well, she added.
“There are technologies that can help. Women can do a self-collected specimen and send that directly to a lab for testing.” Dr. Barnabas revealed. If the screening results are positive, a women will need to follow up with a physician, but “most of the time, the results are negative,” she noted. “To be able to do the first test on your own can really help us increase coverage. We know from multiple studies that a patient-collected specimen is as good as a doctor-collected specimen for doing that first test.”
Currently in the United States, women who received HPV vaccination are still being screened for cervical cancer. “We are hoping that new guidelines will give us guidance on whether we can screen less frequently and follow people closely. We are seeing very, very low rates of HPV among people who have been vaccinated.” Dr. Barnabas said. “We will continue to do our due diligence and follow the data, but it makes sense that we may be able to screen less frequently.”
Screening recommendations call for testing every 3 years, but “we are seeing changes in the way we screen for HPV,” Dr. -Barnabas said. “HPV testing is highly recommended and a higher-quality test than the Pap smear,” Dr. Barnabas said. “And again, that specimen can be self-collected.”
Screening Women in Their 40s and 50s
A study on the increasing incidence of stage IV cervical cancer in the United States found the following: “Black women had a higher incidence of distant-stage disease compared with White women. However, White women had a greater annual increase, particularly in adenocarcinomas.”6 The greatest rise—4.5% annually—in distant cervical cancer occurred among White women between the ages of 41 and 44 who lived in the South. “Compared with Black women, White women also have lower rates of guideline screening and vaccination,” the researchers reported.
“Screening is very important” for women in their 40s and 50s now and less likely to have been vaccinated against HPV,” said Dr. Barnabas. “One of the sad things about cervical cancer is that it affects women in their mid-adult years, when they are most productive,” she added.
“The WHO recommends screening at about age 35 and again after age 45, and we should be able to do at least that in the United States,” according to Dr Barnabas. “Our own guidelines call for more frequent screening, but women who have never been screened have a much higher risk of cervical cancer. In the United States, the vaccine is approved up to age 45, and we should be thinking about who else can be vaccinated to prevent people from acquiring infections.”
Although the CDC generally recommends routine HPV vaccination at age 11 or 12 through age 26, “some adults aged 27 through 45 might decide to get the HPV vaccine based on discussion with their clinicians if they did not get adequately vaccinated when they were younger.”7 In addition to the HPV-16/18 vaccine, there is also a “nine-valent vaccine that protects against nine types of HPV,” Dr. Barnabas explained. “Most people have probably not been exposed to all the types, and if they don’t have them at the time of vaccination, they could still benefit from the vaccine.”
DISCLOSURE: Dr. Barnabas has received funding from Regeneron Pharmaceuticals, and has served as a paid consultant on a trial data and monitoring committee for Gilead Sciences.
REFERENCES
1. World Health Organization: Cervical cancer elimination initiative. Available at https://www.who.int/initiatives/cervical-cancer-elimination-initiative. Accessed October 19, 2022.
2. Johnson S: How Rwanda could become one of the first countries to wipe out cervical cancer. August 18, 2022. Available at https://www.theguardian.com/global-development/2022/aug/18/how-rwanda-could-become-one-of-the-first-countries-to-wipe-out-cervical-cancer-acc. Accessed October 19, 2022.
3. Shahmoradi Z, Damgacioglu H, Montealegre J, et al: Prevalence of human papillomavirus infection among women born in the 1990s vs the 1980s and association with HPV vaccination in the US. JAMA Health Forum 3:e222706, 2022.
4. Barnabas RV, Brown ER, Onono MA, et al: Efficacy of single-dose human papillomavirus vaccination among young African women. NEJM Evid 1:EVIDoa2100056, 2022.
5. Kechagias KS, Kalliala I, Bowden SJ, et al: Role of human papillomavirus (HPV) vaccination on HPV infection and recurrence of HPV related disease after local surgical treatment: Systematic review and meta-analysis. BMJ 378:e070135, 2022.
6. Francoeur AA, Liao CI, Casear MA, et al: The increasing incidence of stage IV cervical cancer in the USA: What factors are related? Int J Gynecol Cancer. August 18, 2022 (early release online).
7. Centers for Disease Control and Prevention: HPV vaccination recommendations. Available at https://www.cdc.gov/vaccines/vpd/hpv/hcp/recommendations.html. Accessed October 19, 2022.
