News & Views — HPV: Notes from IPVC2023
Published on in Vaccine Update for Healthcare Providers
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Published on in Vaccine Update for Healthcare Providers
In mid-April, we had the opportunity to meet with colleagues and partners in Washington, D.C., at the 35th International Papillomavirus Conference & Basic, Clinical and Public Health Scientific Workshops (IPVC 2023). This conference is unique in that the sole focus is papillomaviruses, and attendees range from bench scientists to public health officials to frontline caregivers. The beauty of this model is that even though the conference has tracks for basic science, clinical science and public health, attendees don’t need to “stay in their own lane.” They can move back and forth between lectures, catching up on the latest animal models and then learning about cervical cancer screening barriers in low- and middle-income countries all in the same day.
The Vaccine Education Center (VEC) team was there as part of the “One Less Worry” campaign’s partner pavilion. The “One Less Worry” campaign is a program of the International Papillomavirus Society that seeks to educate about and improve global understanding of human papillomavirus (HPV) risks and prevention.
Here are some takeaways from the conference that we thought might be of interest to our readers.
Often the questions that we receive in the VEC stem from confusion and a lack of understanding of HPV infections. Some of the points made during this conference served as a reminder about the complexities of HPV infection, making the confusion among laypersons understandable.
When a person is infected with HPV, one of two things can happen:
Persistence is described as having HPV-positive tests in two or more consecutive samples. However, because, as described above, HPV can continue to replicate but not be detectable, clearance is more difficult to define. As such, from a clinical standpoint, clearance means the individual has tested negative for HPV. It does not mean, however, that the virus is no longer infecting the person.
Because clearance means the virus has not been detected in samples, but it can still be causing infection, it is not surprising that the virus could be detected intermittently. When studies have evaluated several samples from the same individual over time, they have confirmed this to be the case. Likewise, when a series of samples have been taken from the same individual, studies have confirmed that often people are infected with multiple types of HPV at the same time.
This paper by Brown and colleagues from 2005 demonstrates these points.
HPV16 is most commonly isolated from HPV-caused cancerous tumors, regardless of the location of the cancer (cervix, vulva, vagina, anus, penis, oropharynx, oral cavity or larynx).
However, while HPV16 is the most common cause of cervical cancer around the globe, the other predominant types of HPV vary somewhat by geographic region. Globally, HPV18 is the second most common type of HPV isolated from invasive cervical cancers, but it is not always the second most common type isolated from cytologically normal samples. Except for HPV35, which accounts for 2% to 5% of cervical cancers in Africa, the other common types are contained in the nonavalent HPV vaccine, Gardasil®9. In addition to types 16 and 18, other common types found in cervical cancer samples, and Gardasil-9, include 45, 31, 33, 52 and 58. The other two types of HPV covered by the vaccine, types 6 and 11, do not cause cancer. These so-called “low risk” types are the most common causes of genital warts.
Low-risk types of HPV tend to clear more quickly than high-risk types; however, the median period of positivity is several months, even for those that resolve more quickly. In a 2013 study by Jaisamrarn and colleagues, HPV16 and HPV31 were the least likely to clear. Median months to clearance ranged from about eight months for non-cancerous types to about 17 months for HPV16. A meta-analysis by Rositch and colleagues, also published in 2013, similarly found that about half of HPV infections last six to 12 months.
Sometimes a positive HPV test leads to questions about when the infection was acquired. Studies have shown that both new partners and total number of lifetime partners are associated with HPV positive tests. However, as Rositch and colleagues showed in a 2012 evaluation of 35- to 60-year-old women, only 13% to 27% of samples with detectable HPV DNA could be attributed to a new partner, suggesting that infections often linger for years. In the same study, 72% of the individuals with DNA-positive samples reported having five or more lifetime partners.
The IPVC2023 conference had an excitement in the air. Part of this was because the group had not met in person for five years, but part of it was because of scientific progress. Two of the most exciting advances related to the effectiveness of a single dose of HPV vaccine and global planning for elimination of cervical cancer.
In 2022, the World Health Organization (WHO) indicated that HPV vaccine could be used off-label as a single dose vaccine in those 9 to 20 years of age. The first country to make the transition was Cap Verde in Africa. In the same year, the Joint Committee on Vaccination and Immunisation (JCVI) in the United Kingdom (UK) also indicated that those younger than 25 years of age in the UK could get a single dose, and in early 2023, Australia moved to a single-dose schedule. Several other countries are currently using a one-dose schedule or planning to transition to one, including several Gavi-funded country programs.
Scientific studies evaluating the potential to protect against HPV with only a single dose have been promising, and data continue to be generated:
In 2018, the Director-General of the WHO, Dr. Tedros Adhanom Ghebreyesus, stated “One woman dies of cervical cancer every two minutes … Each one is a tragedy, and we can prevent it.” With that in mind, the WHO set 2030 targets toward cervical cancer elimination. They include aiming to have:
While the thought of cervical cancer elimination garnered excitement, several speakers made the point that it will take many years to reach this goal and current efforts are lagging, particularly in resource-poor countries.
By May 2020, fewer than 30% of low- to middle-income countries had national HPV vaccine programs. In some countries that do have programs, HPV vaccine supplies continue to be limited, resulting in vaccination programs only for girls. In fact, of 117 countries reporting on their HPV vaccine programs, 77 reported only immunizing girls.
However, even in countries where supply is sufficient and recommendations are inclusive, disparities remain. In the closing plenary, Dr. Douglas Lowy, Principal Deputy Director of the National Cancer Institute, reminded the audience that in the U.S., Hispanic and Black women continue to experience higher rates of cervical cancer and death compared with White women. In fact, the 2020 mortality rate was 3.2 per 100,000 for Black women and 2.5 per 100,000 for Hispanic women, compared with 2.1 per 100,000 for White women. Globally, women in many countries are at even greater risk. In the 2020 cancer statistics report, Malawi had the greatest incidence at 40.1 cases per 100,000 and 28.6 deaths per 100,000.
To see the 2020 cancer statistics, check this paper by Sung and colleagues.
We were excited by all that is happening related to HPV, but we also realized just how much there remains to do. At the VEC, we regularly receive questions from the public about HPV infections, transmission and vaccination, so we know people don’t always understand this virus. And we also know that some people remain concerned about HPV vaccine safety, despite its proven record of safety and efficacy. But in the U.S., as parents and healthcare providers, we are lucky. We have sufficient vaccine supplies and the other resources needed to protect our next generation from the health effects of this virus.
Won’t it be wonderful to say that our life’s work contributed to the elimination of HPV-associated cancers? We can give parents #OneLessWorry.
Contributed by: Charlotte A. Moser, MS, Paul A. Offit, MD
Categories: Vaccine Update May 2023, News and Views About Vaccines
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