Call to Eradicate All Types of HPV Cancers, not Just Cervical

Pam Harrison

March 25, 2021

The World Health Organization's (WHO) call for the elimination of cervical cancer worldwide is a laudable goal, and one that many organizations across the globe have endorsed.

Yet some would say that that goal goes only halfway, and that the real finish line should be to eliminate all vaccine-type HPV infections that cause multiple cancers, in men as well as in women.

One proponent of sweeping HPV prevention is Mark Jit, PhD, from the London School of Hygiene & Tropical Medicine, London, England.

In the long run, the WHO's call to eliminate cervical cancer is "insufficiently ambitious" he writes in a special issue of Preventive Medicine.

"The point is, if you are trying to eliminate cervical cancer, you've run part of the race," he said.

"But why not run that extra third and get rid of the virus, then you never have to worry about it again," Jit elaborated in an interview with Medscape Medical News.

Winning that race, however, is dependent on a gender-neutral HPV vaccination policy, he pointed out.

At present, the WHO advocates only for female vaccination and screening.

Some countries have already taken the matter into their own hands. As of May 2020, 33 countries and four territories have gender-neutral vaccination schedules.

Others are also calling for gender-neutral HPV vaccination to achieve a far wider public health good.

"I completely agree that our ultimate goal should be the elimination of all HPV-related cancers — but we will require gender-neutral vaccination to do it," says Anna Giuliano, PhD, professor and director, Center for Immunization and Infection Research in Cancer, Moffitt Cancer Center, Tampa, Florida.

"The reason why WHO started with cervical cancer elimination is that it is likely to be the first cancer that we can achieve this with and if you look internationally, cervical cancer has the highest burden," Giuliano told Medscape Medical News.

"But it's important to understand that it's not just females who are at risk for HPV disease, men have serious consequences from HPV infection, too," she said.

In fact, rates of HPV-related cancers and mortality in men exceed those for women in countries that have effective cervical cancer screening programs, she points out in an editorial in the same issue of Preventive Medicine.

Rates in men are driven largely by HPV-related oropharyngeal cancer, but not only, Giuliano noted in an interview.

Rates of anal cancer among men who have sex with men (MSM) are at least as high as rates of cervical cancer among women living in the poorest countries of the world, where 85% of cervical cancer deaths now occur, she noted. If MSM are HIV positive, rates of anal cancer are even higher.

Unethical to Leave Males Out?

Arguments in favor of gender-neutral HPV vaccination abound, but the most compelling among them is that society really should give males an opportunity to receive direct protection against all types of HPV infection, Giuliano commented.

Indeed, in the UK, experts argue that it is unethical to leave males out of achieving direct protection against HPV infection, she noted.

With a female-only vaccination strategy, "males are only protected if they stay in a population where there are high female vaccination rates — and very few countries have achieved high rates of vaccine dissemination and have sustained it," she pointed out. But that applies only to heterosexual men, who develop some herd immunity from exposure to vaccinated females; this is not the case for MSM.

On a pragmatic note, a vaccine program that targets a larger number of people against HPV infection — which would be achieved with gender-neutral vaccination — is going to be more resilient against temporary changes in vaccine uptake such as what has happened over the past year.

"During the pandemic, people may have had virtual clinic visits but they haven't had in-person visits, which is what you need for vaccination," Giuliano pointed out. "So over the past year, there has been a major drop in vaccination rates," she said.

Eliminating Cervical Cancer

Currently, the WHO plans for eliminating cervical cancer involve a strategy of vaccinating 90% of girls by the age of 15, screening 70% of women with a high performance test by the age of 35 and again at 45, and treating 90% of women with cervical disease — the so-called "90-70-90" strategy.

Jit agrees that very high levels of vaccine coverage would eradicate the HPV types causing almost all cases of cervical cancer. The same strategy would also sharply reduce the need for preventive measures in the future.

However, as Jit argues, 90% female-only coverage will not be sufficient to eliminate HPV 16 transmission, although 90% coverage in both males and females — namely a gender-neutral strategy — might. To show this, Jit and colleagues used the HPV-ADVISE transmission model in India.

Results from this modeling exercise suggest that 90% coverage of both sexes would bring the prevalence of HPV 16 close to elimination, defined as reducing the prevalence of HPV 16 to below 10 per 100,000 in the population.

In addition, because even at this low level, HPV transmission can be sustained in a small group of sex workers and their clients, achieving 95% coverage of 10-year-old girls who might become female sex workers in the future will likely achieve the goal of HPV 16 elimination, as Jit suggests.

OPSCC Elimination

Elimination of another HPV-related cancer, oropharyngeal squamous cell carcinomas (OPSCCs), is discussed in another paper in the same journal.

HPV-related OPSCCs are mostly associated specifically with HPV 16.

There is currently an epidemic of this cancer among middle-aged men in the Nordic countries of Denmark, Finland, Norway, and Sweden; incidence rates have tripled over the past 30 years, note Tuomas Lehtinen, PhD, FICAN-MID, Tampere, Finland, and colleagues.

They propose a two-step action plan — gender-neutral vaccination in adolescent boys and girls, and a screening program for adults born in 1995 or earlier.

The first step is already underway, and the recent implementation of school-based HPV vaccination programs in the Nordic countries is predicted to gradually decrease the incidence of HPV-related OPSCCs, they write.

"Even if HPV vaccination does not cure established infections, it can prevent re-infection/recurrence of associated lesions in 45% to 65% of individuals with anal or cervical intraepithelial neoplasia," the authors write, "and there is high VE (vaccine efficacy) against oropharyngeal HPV infections as well," they add.

Furthermore, there is a tenfold relative risk of tonsillar and base of tongue cancers in spouses of women diagnosed with invasive anogenital cancer, as researchers also point. "This underlines the importance of breaking genito-oral transmission chains," they note.

The screening of adults born in 1995 for HPV-related OPSCC is still at a planning stage.

In a proof-of-concept study for the stepwise prevention of OPSCC, the authors suggest that target birth cohorts first be stratified and then randomized into serological HPV 16 E6 antibody screening or no screening. HPV 16 antibody-positive women and their spouses then could be invited for HPV vaccination followed by 2 HPV DNA tests.

Unscreened women and their spouses would serve as population-based controls. "Even if gender-neutral vaccination results in rapid elimination of HPV circulation, the effects of persistent, [prevalent] HPV infections on the most HPV-associated tonsillar cancer will continue for decades after HPV circulation has stopped," the authors predict.

The Jit study was funded by the Bill & Melinda Gates Foundation and the National Institute for Health. The Lehtinen study was supported by grants from the Finnish Cancer Society and Tampere Tuberculosis Foundation. Jit and Lehtinen have disclosed no relevant financial relationships. Giuliano serves on the advisory board for Merck, which markets the HPV vaccine Gardasil.

Prev Med. 2021;144:106354, 106462, 106445. Full text, Editorial, Full text

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