response to: CDC recommends HPV vaccine to age 26, and more

From: Rebecca Perkins [mailto: Rbperkin@bu.edu]
Sent: Tuesday, August 20, 2019 8:43 AM
To: Geoff A. Modest, M.D.
Subject: Re: CDC recommends HPV vaccine to age 26, and more

Thanks for highlighting HPV and your great work! And thank you for largely focusing your article on the benefits for the pediatric population.

 I did want to add that the risk benefit vaccination ratio for adults is very different from kids. The estimated reduction is 193 HPV-related cancer cases per year if the entire adult population is vaccinated, compared to 25,000 cases averted per year if the entire pediatric and adolescent population is vaccinated. Vaccination of adults in the US will also cause a worldwide shortage of HPV vaccine, delaying cervical cancer reduction efforts in low resource countries which have the majority of cervical cancer burden. So thanks for helping to keep the focus where it will make the most difference--vaccinating kids!

These comments are from Rebecca Perkins, who is deeply involved with HPV trials, policy, education and advocacy on local and national levels (and guided us in developing our successful program in immunizing those 9-10 years old). Her perspective is certainly relevant and important, though I wonder if other countries might begin vaccine production if there were more demand ??

Also, as a perspective, the efficacy of giving the PCV-13 vaccine to adults has quite limited data, but a Netherlands trial found that giving it to 85K people led to 49 subjects getting community-acquired pneumonia vs 90 in the placebo group, and invasive pneumococcal disease in 7 vs 28 people over 4 years, with no difference in deaths (see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457056/ and Bonton MJM. N Engl J Med 2015; 372: 1114) Geoff

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On Aug 20, 2019, at 7:20 AM, Geoff A. Modest, M.D. <GModest@uphams.org> wrote:

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The CDC formally adopted the recommendations that all should be vaccinated with the HPV vaccine until age 26 and that those 27-45 may be vaccinated through shared decision-making (see https://www.cdc.gov/mmwr/volumes/68/wr/mm6832a3.htm

These guidelines follow the ACIP recommendation of 2018 ( http://gmodestmedblogs.blogspot.com/2019/07/acip-new-recommendations-for-hpv-and.html )

Details:

--HPV infections are remarkably common, typically acquired in adolescents and young adults soon after their first sexual activity, though can be acquired at any later time there is a new sex partner

--HPV is associated with a variety of cancers: cervical, anal, penile, vaginal, vulvar, and oropharyngeal

    --there are approx 33,700 HPV-related cancers per year: 12,900 oropharyngeal cancers in men and women (though many more cases in men than women), 10,800 cervical cancers in women, 6000 anal cancers in men and women, and smaller numbers of the other ones; all typically decades after infection [there may be important differences here in women who are HIV positive, where there seems to be more vaginal cancers: see http://gmodestmedblogs.blogspot.com/2016/07/pap-smears-post-hysterectomy-in-hiv.html ]

--in 2018, the FDA approved expanding the ages to include those from age 9 to 45 (see http://gmodestmedblogs.blogspot.com/2018/10/vaccine-approved-to-age-45-tdap-best.html for this FDA recommendation and the data and rationale to support this)

--there are very high antibody conversion rates with the vaccine (on the order of 94-100%), though there was a study finding higher rates overall with delay of the booster dose (see http://gmodestmedblogs.blogspot.com/2018/02/new-adult-and-pedi-immunization.html )

--in 2017 vaccine coverage rates were 65.5%, with dramatic overall decreases of vaccination-type infections (eg, comparing the prevalence of vaccine-type infections from the 4-valent vaccine in 2013-16 to pre-vaccination era, there was a decrease from 11.5% to 1.8% in females 14-19yo and from 18.5% to 5.3% in those 20-24. Including protection even in those not vaccinated (“herd immunity”)

--earlier vaccines, with even fewer HPV types, have documented clinical benefit in deceasing anogenital warts and cervical intraepithelial neoplasia (CIN) [the likely presumption here is that decreasing these early lesions would translate to decreases in cancer in the long run]

--there are few serious adverse events and no deaths associated with the vaccine

--cost effectiveness: $35,000 per quality-adjusted life year gained per current program; expanding male vaccines to age 26 is about $178,000. And extending to age 30 or 45 would be >$300,000

    --number-needed-to-vaccinate (NNV) to prevent one case of anogenital warts was 9, CIN grade 2 or worse was 22 and cancer was 202 in existing program

    --relative numbers by extending male vaccination to 26 would be 40, 450,and 3260, respectively

    --extending through age 45 would be 120, 800, 6500

So, this study reaffirms the prior ACIP recommendations, reinforcing the routine vaccination of all up to age 26 (with appropriate catch-up vaccinations), and allowing vaccination in those up to 45 yo (with “shared decision-making”, presumably targeting those at higher risk of acquiring a new HPV infection). It still remains that the primary target is to vaccinate younger children, since the vaccine is more effective prior to getting HPV infections, the antibody response is more profound in those 14 or less (eg, only 2 doses of vaccine are needed: http://gmodestmedblogs.blogspot.com/2016/11/2-dose-hpv-vaccine-for-girls-and-boys.html ), and these younger ones are more regularly tied into the health care system (easier target population to reach). Our health center and others have been quite successful in targeting 9 year olds, using an “opt-out” approach (ie, the assumption being that all get vaccinated, but allowing parents to opt-out if desired: the emphasis here being that this is an important and effective vaccine for preventing cancer in the future)

There are many prior blogs on HPV and the benefits of vaccination: see http://gmodestmedblogs.blogspot.com/search?q=hpv , including blogs showing:

--the quite high rate of oral HPV in men, on the order of 10+% (see http://gmodestmedblogs.blogspot.com/2017/10/oral-hpv-in-men-and-oropharyngeal-cancer.html )

--understated cervical cancer mortality in women (see http://gmodestmedblogs.blogspot.com/2017/02/understated-cervical-cancer-mortality.html ), with an increased disparity in mortality in black vs white women (eg, population-based results do not correct for hysterectomies, which are much more common in black women)

--as noted in http://gmodestmedblogs.blogspot.com/2019/07/acip-new-recommendations-for-hpv-and.html , the Category B vaccines (for “individual clinical decision-making”) should still be covered by insurance.

geoff​

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