HPV vax: decreased cervical cancer mortality in young women

 

a recent letter-to-the-editor documented a dramatic decrease in cervical cancer deaths in US women younger than 25 years old, over the time period of 1992-2021. This was likely attributable to the advent of the HPV vaccine (see dec cervical cancer mortality in young women JAMA2025 in dropbox, or doi:10.1001/jama.2024.22169)

 

Details:

-- cervical cancer mortality trends were obtained from the National Center for Health Statistics

-- main outcome: the changes in cervical cancer mortality from 1992 to 2021, with specific reference to women <25yo

 

Results:

-- 398 cervical cancer deaths were reported from 1992-2021 in women <25yo

-- between the 3-year cycle of 1992-94 to 2013-15, there was a largely linear gradual decline in the cervical cancer mortality, at a rate of 3.7%/year (-4.8% to -2.1%)

-- the cervical cancer mortality rate then decreased from 2016-2021 at 15.2%/year (-21.9% to -7.8%), and with an overall 62% reduction (see graph on left)

-- this decrease reflected an absolute decrease of 55 deaths in 1992-1994 to 13 in 2019-2021 (see graph on right)

    -- based on the prior rate of decrease, an estimated 26 additional cervical cancer deaths would have been expected

 


 

Commentary:

-- HPV vaccine became available in the US in June 2006 covering 4 serotypes, then the 9-valent one became available in 2015 (which covered the more oncogenic strains of HPV)

-- in a prior study, they found an overall decrease in cervical cancer incidence from 12.39/100K women in 2001 to 9.80/100K in 2019: https://jamanetwork.com/journals/jama/fullarticle/2799049

    -- the biggest decline was in women aged 25-29, which went from 5.36/100K in 2016 to 4.01/100K in 2019, a 7.5% annual decrease of this timeframe (borderline statistical significance); the overall trend in women at all ages was highly statistically significant over time, p<0.001)

    -- for women <25yo (the target of the current study), there was a decrease from 0.24/100K women in 2012 to 0.08/100K women in 2019, a 12.4% annual decline, overall a 65% reduction, and highly statistically significant at p<0.001; and by comparison to the 2001-2012 time period (when the HPV vaccinations first started), there was a 3.1% decline from 0.29/100K in 2001 to 0.24/100K in 2012, with p=0.02

        -- this timing all was consistent with large increases in the protective effect of HPV vaccine

-- this current study followed the previous one assessing mortality rates (the earlier one was incidence rates), finding a pretty dramatic decrease in cervical cancer mortality in women <25yo who were the first cohort to reap the potential benefits of the HPV vaccine (though many of them may have only received the less potent 4-valent vaccine)

-- the initial gradual decrease may well reflect improved screening and evaluations, and perhaps education on the causation of HPV with cervical cancer and use of condoms

-- this current article came out recently, reinforcing the slew of prior studies showing that HPV vaccination is not just safe, but is remarkably effective in decreasing cervical cancer and likely oropharyngeal and other cancers: for the epidemiology and some of the more recent studies on changes in precancerous cervical pathology associated with vaccination, see https://gmodestmedblogs.blogspot.com/2024/05/hpv-related-cancers-oropharyngeal-is.html

    -- cervical cancer: cervical cancer is basically an HPV-associated cancer, leading to the CDC’s strong recommendation for HPV vaccines be given to all teens until age 26, with the option to continue to age 45 since the vaccine was so effective

        -- a Scottish study found a 92% reduction in high-grade dysplasia from the pre-immunization to immunization time-period, and a 77% reduction in moderate-grade dysplasia; this protection extended to non-vaccinated individuals, suggesting herd immunity (https://gmodestmedblogs.blogspot.com/2019/04/hpv-vaccination-dramatic-decrease-in.html)

            -- another study in this blog found a dramatic (97%) decrease in high-grade cervical, vulvar, and vaginal pathology in those women randomized to the newer HPV-9 vaccine that covered the more oncogenic HPV serotypes vs the older 4-serotype one

    -- oropharyngeal cancer: the majority of these cancers are related to HPV infection (>70%), occur most frequently in men, and are largely (>90%) associated with HPV-type 16. vaccination dramatically decreases HPV-16 (90-100% developed HPV-16 specific antibodies). https://pmc.ncbi.nlm.nih.gov/articles/PMC8310210/#sec3-viruses-13-01339 and https://pmc.ncbi.nlm.nih.gov/articles/PMC4299160/. it is too soon now to know the actual changes in clinical oropharyngeal cancers (which occurs later in life), but this current information is pretty suggestive. see https://gmodestmedblogs.blogspot.com/2024/05/hpv-related-cancers-oropharyngeal-is.html for recent data

    -- anal and penile cancers: about 2/3 of penile cancers and >90% of anal cancers are associated with HPV:  https://gmodestmedblogs.blogspot.com/2017/02/understated-cervical-cancer-mortality.html,

 

Limitations:

-- there is a quite evident association between the initiation of HPV vaccinations and both the incidence and mortality of cervical cancer in those women <25yo, but:

    -- we do not have enough granular data in either of these studies to assess whether this reduction, on an individual level, occurred specifically to those individuals who had received the vaccine

   -- if the vaccine were very effective, the decreased incidence of cervical cancer attributable to vaccination would likely be much higher than what was found in this study (though i have not seen applicable studies reflecting the cutpoints for effective herd immunity, since the vaccine seems to be protective of non-vaccinated women as well)

        -- it should be noted that the 9-valent vaccine (which covers the most important oncogenic strains of HPV) was not released until 2015, so the results on cervical cancer mortality will likely improve dramatically over time, when immunization with this much better vaccine will be more widespread

-- we do not have any information about other potential risk factors, including multiple sexual partners, sex at an early age, smoking, family history of cervical cancer, immunodeficiency (eg HIV), etc. or other psychosocial risk factors that might have played a role, limiting the generalizability of the results

-- as expected, there were few mortality events in the young cohort evaluated in this study. There was no specific statistical analysis in this article, though the prior study on declining incidence of cervical cancer did find a highly statistically significant decline (p<0.001). and in this current mortality study, the confidence intervals were consistent with a statistically significant decline

 

so,

--as we know, after the current US elections there will likely be upcoming huge changes in the public health approach to vaccinations:

    -- the rates of HPV vaccine have been lower in males than females (in 2022, 34.6% of boys 9-17 had received at least one dose of vaccine vs 42.9% of girls); overall 38.6% of children aged 9-17 had at least one HPV vaccination dose, increasing with age such that in those aged 15-17 it was in 56.9% overall: https://www.cdc.gov/nchs/data/databriefs/db495.pdf

-- this issue of HPV vaccination has been distorted, with evident prevarication (ie lying) by RFK Jr, the quite likely upcoming head of Health and Human Services, who is trying to present himself as not-really-so-opposed to vaccines despite his many antivaccine diatribes:

    -- he clearly has stated that HPV vaccine is unsafe, despite loads of data to the contrary: https://www.ascp.org/news/external-news/industry-news/2025/01/31/HPV-Vaccine-Is-Safe-Despite-RFK-Jr-s-Claims-CDC-Says?srsltid=AfmBOoowvaLuVFCcTqocpc0GusFm6EJmfHE0xf07oC0QT4yBOTT1le0l

        -- an Australian study of 11 years with the HPV-4 vaccine and 9 million doses found a low incidence of syncope in those 12-13yo (29.6 per 100K doses of vaccine in females and 7.1/100K in males, with higher rates in the younger adolescents); and 0.32/100K for anaphylaxis. There were low rates but no expected increase from the vaccine for autoimmune disease, postural orthostatic tachycardia syndrome, primary ovarian insufficiency, Guillan-Barre syndrome, complex regional pain syndrome and venous thromboembolism: https://www.sciencedirect.com/science/article/pii/S0264410X20308252

    -- RFK Jr is involved in a lawsuit against Merck, the HPV vaccine Gardasil developer, citing erroneously that there are "many hundreds of cases" of adverse effects, reimbursing him directly to 10% of the fees from the law firm pursuing this issue and $856,559 in 2023: https://www.statnews.com/2025/01/31/rfk-jr-hhs-gardasil-litigation-fees-divest-son-wisner-baum/; https://abcnews.go.com/Politics/major-reversal-kennedy-tells-senators-money-vaccine-lawsuit/story?id=118321043 

    -- he recently reported that if he is confirmed, he will divest from the lawsuit, but will give his share of the proceeds of the lawsuit to his son Conor, who just so happens to be a lawyer in that law firm pursuing the lawsuit..... https://www.nytimes.com/2025/01/31/health/rfk-jr-gardasil-hpv-lawsuits-confirmation.html

    -- and there is no assurances that he will not personally profit from subsequent lawsuits against other products

    -- RFK Jr also came out strongly against both the polio and measles vaccines, also very highly protective with potentially disastrous effects if these are curtailed: https://gmodestmedblogs.blogspot.com/2024/12/getting-rid-of-vaccines.html 

-- one concern about HPV vaccine is that there has clearly been a backlash against all vaccines in our current era (error?), leading to decreases of many vaccines, eg flu vaccine declined especially in white children and adults <65yo: https://www.cdc.gov/fluvaxview/coverage-by-season/2023-2024.html). In fact HPV coverage, though previously increasing, has actually had a declined since the beginning of the COVID-19 pandemic from 79.3% in 2022 to 75.9% in 2024 among US adolescents

 

-- so, the current beat of anti-science, anti-public health, pro-conspiracy theories, remarkably unethical positions and outright lying (eg, that RFK is not anti-vaccination and is open to his reviewing "the science" (as the blatantly non-scientist that he is) are likely to intensify if RFK, Jr is confirmed)

-- not only will there likely be a rollback of proven and critically important public health measures, but there will likely be a dramatic skew of future research support bent towards his anti-science proclivities

-- the anticipated pending anti-vaccine agenda will likely be implemented, and will likely be associated with severely undercutting the federal ability to maintain a vigorous public health system, making it harder to identify public health issues (there will likely to be more health problems from lots of industry deregulation, exposure to carcinogenic chemicals in the atmosphere, less research into the spread of new deadly microbes or potential vaccines/therapies, etc). As before, trump effectively dissolved the National Security Council unit dealing with future pandemics. Likely more coming...

 

as i concluded the last blog on polio and measles, "indeed, we are now in for a roller-coaster ride, one with a rickety frame and without guardrails". it now seems that there are no seatbelts or even seats as well...

 

geoff

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