Recently, I was pointed to a blog post that tried to claim that the HPV vaccine did nothing for the risk of cervical cancer and also tried to manipulate some data that implied the vaccine increased the risk. The author tried to “prove” that data from Australia showed that the HPV vaccine increased the risk of cervical cancer — the facts show that the vaccine works.

Unfortunately, I have found that trying to debunk these bogus “studies” is a waste of time. They cherry-pick data that supports their anti-vaccine claims. So, instead of trying to debunk a non-peer-reviewed blog post from an anti-vaccine activist, I need to present the peer-reviewed articles that support the claim that the HPV vaccine actually reduces the risk of cervical cancer.

Further, these HPV vaccine deniers tend to ignore the affirmative evidence by trying to massage data to support their claims rather than doing hard work such as setting up a large clinical trial or observational study that supports their claims. The problem, of course, is that by doing so, they will probably provide more evidence that the HPV vaccine does what we claim it does — prevent cervical and many other cancers.

This post will review a few of the largest studies that show that the HPV vaccine prevents cervical cancer. It is my affirmative defense of the effectiveness of the HPV vaccine.

All about HPV and HPV vaccines

I know I cut and paste this section to every article I write about HPV vaccines, but it’s the first step to HPV vaccine myth debunking. Some readers may be coming here for the first time and should know how the HPV vaccine lowers cancer risks. 

However, I try to update this section when necessary with new information about either the disease or the vaccine. If you’ve read this section 47 times, skip to the next section where I discuss the key points of this article.

Genital and oral human papillomavirus (HPV) infections are the most common sexually transmitted infections (STI) in the USA.  HPV is generally transmitted from personal contact during vaginal, anal, or oral sex.

It’s important to note that there are more than 150 strains or subtypes of HPV that can infect humans – however, only 40 of these strains are linked to one or more different cancers. Of those 40 strains, most are fairly rare.

Although the early symptoms of HPV infections aren’t serious and many HPV infections resolve themselves without long-term harm, HPV infections are causally linked to many types of cancers in men and women. According to current medical research, here are some of the cancers that are linked to HPV:

• Cervical cancer
• Vulvar cancer
• Vaginal cancer
• Anal cancer
• Oropharyngeal cancer (throat cancer)
• Penile cancer

In addition, there is some evidence that HPV infections are causally linked to skin and prostate cancers. The link to skin cancer is still preliminary, but there is much stronger evidence that HPV is linked to many prostate cancers.

HPV is believed to cause nearly 5% of all new cancers across the world, making it almost as dangerous as tobacco in that respect. According to published research, roughly 42 million persons in the USA are infected with disease-associated HPV, and 13 million persons acquire a new infection each year. Most individuals don’t even know they have the infection until the onset of cancer. The CDC states that over 37,000 HPV-related cancers are diagnosed in the USA every year. It is probably several times that amount worldwide.

There were two HPV vaccines on the world market before 2014. GSK, also known as GlaxoSmithKline, produced Cervarix, a bivalent (protects against two HPV strains) vaccine. It has been withdrawn from the US market (although available in many other markets), because of the competition from the quadrivalent (immunizes against four different HPV strains) and 9-valent (against nine HPV strains) Gardasil vaccines.

Merck manufactures Gardasil, which is probably the most popular HPV vaccine in the world. The first version of the vaccine, quadrivalent Gardasil, targets the two HPV genotypes known to cause about 70% of cervical cancer and two other HPV genotypes that cause genital warts. In Europe and other markets, Gardasil is known as Silgard.

The newer Gardasil 9, approved by the FDA in 2014, is a 9-valent vaccine, protecting against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. It targets the four HPV strains found in the quadrivalent version, along with five additional ones that are linked to cervical and other HPV-related cancers. Both versions of Gardasil are prophylactic, meant to be given to females or males before they become exposed to possible HPV infection through intimate contact.

Gardasil is one of the easiest and best ways to prevent a few dangerous and, to abuse the definition slightly, common cancers that afflict men and women. Without a doubt, the HPV vaccine prevents cancer.

Currently, in the United States, the Advisory Committee on Immunization Practices (ACIP) recommends that preteen girls and boys aged 11 or 12 be vaccinated against HPV. The HPV vaccine is also recommended for teenage girls and young women up to the age of 26 who did not receive it when they were younger, and boys and young men up to the age of 21.

Let me sum this up so you get this summary if you leave this section with nothing else. HPV is a sexually transmitted disease. HPV causes 37,000 cancers a year in the USA alone. The HPV vaccine prevents one from becoming infected by HPV, which means you are protected from these cancers.

HPV vaccine and cervical cancer, first paper

In a paper published on 22 January 2024 in the Journal of the National Cancer Institute, Tim J Palmer, MD, FRCPath, Public Health Scotland, Glasgow, UK, and colleagues monitored the records of all women born between 1988 and 1996 who were eligible for cancer screening, about 450,000 women. Of that group, 40,000 were vaccinated between the ages of 12 and 13, and 124,000 received the vaccines at or after 14 years of age. The remaining women, nearly 300,000, were not vaccinated.

The types of vaccine administered to the cohorts monitored in the study changed as newer ones became available, covering more types of HPV. Until 2012, the vaccine in use was the bivalent Cervarix. Then the quadrivalent Gardasil was administered until 2023. After that point, the 9-valent Gardasil 9 was introduced.

Here are the key results from the study:

• There were 8.4 cases of cervical cancer per 100,000 unvaccinated women.
• NO cases of cervical cancer were found among the women who were vaccinated before they turned 14, even if they had only received one or two doses of the vaccine rather than the full, three-dose protocol.
• Women who received the three-dose protocol between the ages of 14 and 22 also benefited significantly. The incidence of cervical cancer in this group was 3.2 cases per 100,000 women, over 2.5X lower rate than the unvaccinated group.

The authors concluded:

Our findings confirm that the bivalent vaccine prevents the development of invasive cervical cancer and that even 1 or 2 doses 1 month apart confer benefit if given at 12-13 years of age. At older ages, 3 doses are required for statistically significant vaccine effectiveness.

HPV vaccine and cervical cancer, second and third paper

In a paper published on 3 November 2021 in The Lancet, Peter Sasieni, Innovation Hub, Guy’s Cancer Centre, Guy’s Hospital, London, UK, and colleagues studied the change in cervical cancer and cervical intraepithelial neoplasia 3 (CIN 3), grade 3 cervical dysplasia, incidences since the introduction of the HPV vaccine for girls in England in 2008.

Those individuals are now adults in their 20s, and the study showed that, compared to the unvaccinated cohort, the HPV vaccine group had the following reduction in cervical cancer rates:

• 34% reduction in the cohort that first received the vaccine at 16-18 years (school year 12-13).
• 62% reduction in 14-16 years (school year 10-11).
• 87% reduction in 12-13 years (school year 8).

The reduction in cervical cancer rate decreases with each year older of the first vaccination – this may be a result of previous exposure to HPV before receiving the vaccine or there is less time for the development of cervical cancer, so the numbers are lower for those who were older at time of vaccination.

The risk reduction for CIN 3, the pre-cancerous stage, showed a similarly remarkable reduction compared to the unvaccinated cohort:

• 39% for the cohort that first received the vaccine at 16-18 years (school year 12-13).
• 75% for 14-16 years (school year 10-11).
• 97% for 12-13 years (school year 8).

The researchers estimated that by 30 June 2019, there had been 448 fewer than-expected cervical cancers and 17,235 fewer than-expected cases of CIN3 in vaccinated in England compared to unvaccinated cohorts.

The authors concluded:

We observed a substantial reduction in cervical cancer and incidence of CIN3 in young women after the introduction of the HPV immunisation programme in England, especially in individuals who were offered the vaccine at age 12–13 years. The HPV immunisation programme has successfully almost eliminated cervical cancer in women born since Sept 1, 1995.

In a follow-up study published on 15 May 2024 in The BMJ, Peter Sasieni, Centre for Cancer Screening, Prevention and Early Diagnosis, Wolfson Institute of Population Health, Queen Mary University of London, UK, and colleagues attempted to replicate their previous work described above after 12 additional months of follow-up.

Here are the key results:

• In the birth cohort of women offered vaccination routinely at age 12-13 years, adjusted age-standardized incidence rates of cervical cancer and CIN3 in the additional 12 months of follow-up (1 July 2019 to 30 June 2020) were, respectively, 83.9% and 94.3% lower than in the reference cohort of women who were never offered HPV vaccination.
• By mid-2020, HPV vaccination had prevented an estimated 687 cervical cancers and 23,192 CIN3s.

This study confirms their previous study that showed that the HPV vaccine was extremely effective in reducing the rate of cervical cancers.

Fourth paper

In a study published on 3 April 2019 in The BMJ, Tim J Palmer MD, FRCPath, The University of Edinburgh, Edinburgh, Scotland, and colleagues quantified the effect on cervical disease at age 20 years of immunization with the bivalent HPV vaccine at age 12-13 years in Scotland which screened women for cervical cancer from the age 20 (in 2016, it changed that to 25 in line with the rest of the UK.

The researchers had very detailed information about cervical cancer screening in the first cohort of fully vaccinated girls and of the girls in the catchup program.

Here are the key results:

• 138,692 records were analyzed. This is a large number, which provides us with better statistical measurements of the reduction of cervical cancer rates
• Compared with unvaccinated women born in 1988, vaccinated women born in 1995 and 1996 showed an 89% reduction of cervical intraepithelial neoplasia (CIN) grade 3 or worse, from 0.59% to 0.06%.
• An 88% reduction in CIN grade 2 or worse from 1.44% to 0.17%.
• A 79% reduction in CIN grade 1 from 0.69% to 0.15%.
• Importantly, younger age at the time of immunization was associated with increasing vaccine effectiveness: 86% for CIN grade 3 or worse for women vaccinated at age 12-13 compared with 51% for women vaccinated at age 17.
• Evidence of herd protection against high-grade cervical disease was found in unvaccinated girls in the 1995 and 1996 cohorts.

I hate to use this particular word, but these are awesome results. One of the anti-vaccine tropes about the HPV vaccine is that we have no data showing it actually reduces the rates of cervical cancer and pre-cancer. The 89% reduction in CIN grade 3, the worst form of cervical pre-cancer.

In an accompanying editorial, Julia ML Brotherton, MD, wrote:

The findings are dramatic and document a considerable reduction in high-grade cervical disease over time. The authors estimate a vaccine effectiveness of 86% (95% confidence interval 75% to 92%) for the most severe outcome of cervical intraepithelial neoplasia (CIN) grade 3 or worse in women fully vaccinated at ages 12-13 compared with the unvaccinated cohort. Notably, they report a large reduction in CIN grade 3 or worse in the most recent cohort of women compared with the pre-vaccination cohort, whether they were vaccinated or not (from a rate of 0.59% to 0.06%, an 89% decline), suggesting that interruption of HPV transmission in Scotland has created substantial herd protection.

Summary

My “affirmative defense” of the HPV vaccine is quite clear — large population studies that have been published in numerous peer-reviewed journals show that the HPV vaccine is highly effective in preventing cervical cancer and cervical intraepithelial neoplasia 3.

As JaNiese E. Jensen and colleagues wrote in a review of HPV and cancer, “The vaccine prevents cervical cancer with near 100% efficacy if given prior to first sexual activity.”

Despite the false claims of anti-vaccine activists, real scientific evidence shows that the HPV vaccine is extremely effective in reducing the risk of HPV-related cervical cancers, especially if the vaccine is given to younger children before they become sexually active.

People are always asking when we will have cancer vaccines — well, the HPV vaccine is one.

Citations

• Brotherton JML. The remarkable impact of bivalent HPV vaccine in Scotland. BMJ. 2019 Apr 3;365:l1375. doi: 10.1136/bmj.l1375. PMID: 30944088.
• Falcaro M, Soldan K, Ndlela B, Sasieni P. Effect of the HPV vaccination programme on incidence of cervical cancer and grade 3 cervical intraepithelial neoplasia by socioeconomic deprivation in England: population based observational study. BMJ. 2024 May 15;385:e077341. doi: 10.1136/bmj-2023-077341. PMID: 38749552; PMCID: PMC11094700.
• Falcaro M, Castañon A, Ndlela B, Checchi M, Soldan K, Lopez-Bernal J, Elliss-Brookes L, Sasieni P. The effects of the national HPV vaccination programme in England, UK, on cervical cancer and grade 3 cervical intraepithelial neoplasia incidence: a register-based observational study. Lancet. 2021 Dec 4;398(10316):2084-2092. doi: 10.1016/S0140-6736(21)02178-4. Epub 2021 Nov 3. PMID: 34741816.
• Jensen JE, Becker GL, Jackson JB, Rysavy MB. Human Papillomavirus and Associated Cancers: A Review. Viruses. 2024 Apr 26;16(5):680. doi: 10.3390/v16050680. PMID: 38793561; PMCID: PMC11125882.
• Palmer TJ, Kavanagh K, Cuschieri K, Cameron R, Graham C, Wilson A, Roy K. Invasive cervical cancer incidence following bivalent human papillomavirus vaccination: a population-based observational study of age at immunization, dose, and deprivation. J Natl Cancer Inst. 2024 Jun 7;116(6):857-865. doi: 10.1093/jnci/djad263. PMID: 38247547.
• Palmer T, Wallace L, Pollock KG, Cuschieri K, Robertson C, Kavanagh K, Cruickshank M. Prevalence of cervical disease at age 20 after immunisation with bivalent HPV vaccine at age 12-13 in Scotland: retrospective population study. BMJ. 2019 Apr 3;365:l1161. doi: 10.1136/bmj.l1161. PMID: 30944092; PMCID: PMC6446188.