I have written nearly 200 articles on the HPV vaccine, many on Gardasil vaccine effectiveness, one of the most important issues about this important cancer-preventing vaccine. But that’s so much data, so I wanted to publish one article that reviewed the largest and best peer-reviewed articles that support the claims of Gardasil vaccine effectiveness.
My goal is to make this article your “go-to” source for the best and clearest evidence that the HPV vaccine not only prevents HPV infections but it also significantly decreases cancer risks.
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 they ought to know just how the HPV vaccine prevents cancer.
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, just skip down to the next section where I discuss the key point 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:
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 the CDC, roughly 79 million Americans are infected with HPV – approximately 14 million Americans contract a new HPV every year. Most individuals don’t even know they have the infection until the onset of cancer. The CDC also states that over 43,000 HPV-related cancers are diagnosed in the USA every year. It may be 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, 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 are vaccinated against HPV. The immunization 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 teenage boys and young men up to the age of 21.
Let me sum this all up so that if you come away from this section with nothing else, you get this summary. HPV is a sexually transmitted disease. HPV causes 43,000 cancers a year in the USA alone. The HPV vaccine prevents becoming infected by HPV, which means you are protected from these cancers.
HPV linked to cancer
In a recent article published in the Centers for Disease Control and Prevention (CDC) Morbidity and Mortality Weekly Report, CDC researcher Elizabeth A Van Dyne, MD et al. examined the incidence of HPV-associated cancers in the USA from 1999 to 2015. Their results are surprising and should make us redouble our efforts to increase the uptake of the HPV vaccine.
The researchers found that oropharyngeal squamous cell carcinoma (SCC) (see Note 2) is now the most common of HPV-associated cancers in the USA. SCC incidence rates, from 1999 through 2015, increased by 2.7% per year for men and 0.8% per year among women.
Oropharyngeal cancer has now replaced cervical cancer as number 1 on the list of HPV-associated cancers. In 2015, there were a total of 11.788 cervical cancers compared to 18,917 oropharyngeal SCC’s.
Anti-vaxxers often try to claim that HPV is “only” linked to cervical cancer, but as you can see, it’s a lot more than that. And those cancers can affect both men and women.
According to the report, the decline in cervical cancer is part of a long-term trend, since the 1950s, which has resulted from better guidelines and attention to cervical screening. On the other hand, the increase in oropharyngeal SCC may be due to changing sexual behaviors over the past 15-20 years, including unprotected oral sex, especially among white men, who report having the highest number of sexual partners and performing oral sex at a younger age.
The study also stated that in 1999, there were a total of 30,115 new cases of HPV-associated cancers. However, in 2015, there were 43,371 cases. The rate of HPV-associated cancers dropped by 0.4% annually during the study period, whereas it increased by 2.4% annually among men.
To obtain this data, the CDC analyzed data from their own National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program for all years from 1999 to 2015.
There is a limitation to these registries – they track the incidence of invasive cancers, but they do not track the HPV status of individual cases of cancer. The researchers adjusted the data using published statistics on the percentage of each cancer that is linked to HPV. In the United States, HPV DNA was found in 91% of cervical, 91% of anal, 75% of vaginal, 70% of oropharyngeal, 69% of vulvar, and 63% of penile cancers.
Gardasil vaccine effectiveness – the best one
A study of nearly 1.7 million Swedish women comparing vaccinated and unvaccinated groups showed an almost 96% decrease in the risk of invasive cervical cancer in women who received the HPV vaccine before the age of 17.
Jiayao Lei, Ph.D. and colleagues, in a paper published (reviewed here) in the New England Journal of Medicine on October 1, 2020, examined the risk of invasive cervical cancer in 1,672,983 Swedish women who received the quadrivalent HPV vaccine compared to those who did not. This cohort study included an open population of girls and women 10 to 30 years of age who were living in Sweden from 2006 through 2017.
The results can be summed up with this one graphic:
But, of course, we should review the most important results from this study:
- The study population included 1,672,983 girls and women 10 to 30 years of age, 527,871 of whom received at least one dose of HPV vaccine during the study period. Of the vaccinated group, 438,939 (83.2%) initiated vaccination before the age of 17 years.
- During the study period, cervical cancer was diagnosed in 19 women who had received the quadrivalent HPV vaccine, and in 538 women who had not received the vaccine – just the raw numbers show an incredible difference in the risks of cervical cancer.
- The cumulative incidence of cervical cancer increased rapidly at 23 years old because this is the age when Swedish women first participate in cervical cancer screening programs.
- At 30 years of age, the cumulative incidence of cervical cancer was 94 per 100,000 in unvaccinated women and 47 per 100,000 in vaccinated.
- Among women who initiated their HPV vaccination at the age of 17-30 years, the cumulative incidence was 54 per 100,00.
- Among women who initiated the vaccination before the age of 17, the cumulative incidence was 4 cases per 100,000. That is almost a 96% decrease in the risk of cervical cancer in those women who get the HPV vaccine early over those who are unvaccinated.
- After adjusting for age at follow-up, all vaccinated women had a 49% decrease in the risk of cervical cancer over unvaccinated women.
- After fully adjusting for age and other factors, women who were vaccinated before the age of 17 showed an 88% decrease in the risk of cervical cancer compared to unvaccinated women.
The authors concluded this about Gardasil vaccine effectiveness:
In this large, nationwide study of girls and young women 10 to 30 years of age who had been vaccinated through HPV vaccination programs, we found that HPV vaccination was associated with a substantially reduced risk of invasive cervical cancer.
Gardasil vaccine effectiveness study – powerful
Researchers examined 2200 women who received the HPV vaccine, and none exhibited any signs of invasive cervical cancer. And they determined that the vaccine was effective for at least 12-14 years.
The study, by Susanne K Kjaer et al, was published (reviewed here) in June 2020 by The Lancet’s EClinical Medicine. Young women, 16-23 years of age, from Denmark, Iceland, Norway, and Sweden who had received three quadrivalent HPV vaccine does during a randomized, double-blind, placebo-controlled study were followed for effectiveness for an additional 10 or more years.
The researchers took tissue samples during organized cervical cancer screening programs and were adjudicated for histopathology diagnoses and also tested for HPV DNA. Serum was also collected in year 9 and year 14 of the study to assess antibody responses.
The results were:
- No cases of HPV16/18-related high-grade cervical dysplasia were observed in the vaccinated population (n=2121).
- HPV vaccine effectiveness was calculated to be 100% for at least 12 years, possibly through 14 years.
- Seropositivity rates were estimated to be >90% against HPV6/11/16/18 (the four HPV types covered by the quadrivalent HPV vaccine) using a very sensitive IgG immunoassay.
The authors provided this conclusion about Gardasil vaccine effectiveness:
Vaccination of young women with qHPV vaccine offers durable protection against HPV16/18-related high-grade cervical dysplasia for ≥12 years, with a trend toward continued protection through 14 years post-vaccination, and induces sustained HPV6/11/16/18 antibody responses for up to 14 years post-vaccination. There was no evidence of waning immunity, suggesting no need for a booster dose during that period.
Gardasil vaccine effectiveness – genital warts
A meta-review that included over 13 million participants showed that the HPV vaccine reduced the risk of genital warts by over 97%.
On 28 May 2020, BMC Public Health published a meta-review (reviewed here) that found that the quadrivalent HPV vaccine can prevent genital warts in healthy women and men. The researchers concluded that HPV vaccines should be or continue to be included in routine immunization programs for teens and young adults.
The meta-review include eight randomized clinical trials where HPV or placebos were administered to females or males (in one of the studies). The researchers then compared the number of genital warts cases was compared between the two groups.
The researchers also reviewed eight time-trend studies to assess the population-level effect of Gardasil vaccination by comparing the rate of genital warts between pre- and post-vaccination periods. In this part of the analysis, the researchers found that:
- The HPV vaccine was found to significantly reduce the overall risk of genital warts – odds ratio of 0.03 (an odds ratio of 1.0 means that the vaccine would have no effect, so an odds ratio of 0.03 means that the risk of genital warts is reduced by 97% in the vaccinated group).
- The risk of genital warts in women was substantially lower in the vaccinated group – odds ratio of 0.36.
- Although young men were not vaccinated in this study (part of the study period pre-dated the approval for the disease in young men), the risk of genital warts was reduced in men, probably as a result of indirect protection provided by the vaccination of young women – odds ratio of 0.69.
- The analysis showed that genital warts were reduced in those under 21 years of age compared to older persons, probably since the vaccine has only been available for around 10 years – odds ratio of 0.33.
These results are consistent with many other systematic reviews and meta-analyses that also found that the risk of genital warts was much lower in vaccinated girls.
The authors concluded:
The results from RCTs and time-trend analyses – representing more than 13,000,000 participants – have shown that the quadrivalent HPV vaccine is highly effective in preventing HPV 6/11 related GW both in women and men which gives an additional value to the application of this type of vaccine. Our meta-analysis provides up-to-date information for the public about the effectiveness of HPV vaccination. Teenagers and their parents should acquire better knowledge about HPV infection and prevention. This is of very high importance, because rumours about vaccine safety have been one of the principal obstacles for the acceptance of HPV vaccination by the public. Despite the early implementation of national vaccination programs, in the majority of developed countries coverage rates remain unsatisfactory .
Furthermore, the present work provides reliable information for obstetrician–gynaecologists and other health care providers who should raise the attention of parents and patients for the benefits of HPV vaccination and offer HPV vaccines. Additionally, our results demonstrating strong evidence of quadrivalent HPV vaccine effectiveness can help the governments for making decisions about the implementation of the vaccination. It would be recommended to include the quadrivalent HPV vaccine in routine immunization programme because of its high effectiveness not only against cancer but also against GW.
In summary, our results clearly show that the ecological impact of the quadrivalent HPV vaccine is high and its introduction in many countries is strongly suggested.
Gardasil vaccine effectiveness – cervical cancer
A meta-analysis that examined data on 60 million individuals showed the HPV vaccine reduced the risk of cervical intraepithelial neoplasia grade 2+ in women by 51%.
In an article by Mélanie Drolet et al., published in The Lancet on 26 June 2019, (reviewed here) researchers found robust evidence that the HPV vaccine significantly decreases the risk of precancerous cervical lesions as well as anal-genital warts.
The meta-analysis (considered the pinnacle of the hierarchy of biomedical research) examined data on 60 million individuals over nearly 10 years. The analysis included 65 studies published from February 2014 through October 2018. This new analysis updates a study published in 2015 by the same researchers.
They found the following:
- 5-8 years after receiving the HPV vaccine, the prevalence of HPV 16 and 18 decreased by 83% among girls, age 13-19.
- During the same time period, the prevalence dropped by 66% in women, age 20-24.
- Again, during the same time period, the prevalence of cervical intraepithelial neoplasia grade 2+ (known as CIN2+, see Note 1) decreased by 51% in girls, age 15-19.
- The prevalence of CIN2+ decreased by 31% in women, age 20-24.
- The prevalence of CIN2+ did not decrease in countries with low HPV vaccine coverage.
- The researchers found that with high vaccination coverage, the impact of the HPV vaccine produced substantial herd immunity. They discovered statistically significant decreases in HPV 31, 33, and 45 among girls, ages 20 and younger.
- Notably, they found a 67% decrease in anal-genital warts in girls, ages 15-19, and a 54% decrease in women, ages 20-24.
- Additional evidence in support of a powerful herd effect from HPV vaccination, the rate of anal-genital warts in boys, ages 15-19, decreased by 48%, and in men, ages 20-24, 32%.
The authors wrote about the Gardasil vaccine effectiveness:
Our results provide strong evidence of HPV vaccination working to prevent cervical cancer in real-world settings, as both the cause (high-risk HPV infection) and proximal disease endpoint (CIN2+) are significantly declining. In terms of global policy implications, these results reinforce the recently revised position of WHO recommending HPV vaccination of multiple age cohorts of girls, and provide promising early signs that the WHO call for action on cervical cancer elimination might be possible if sufficient population-level vaccination coverage can be reached.
In an accompanying editorial, also published in The Lancet, Silvia de Sanjose, MD, Ph.D., and Sinead Delany-Moretlwe, MBBCh, Ph.D., stated that greater vaccine coverage is critical to herd immunity, given that the disease burden accounts for more than 80% of deaths attributable to HPV-related cancers in low-income and middle-income countries.
Researchers de Sanjose and Delany-Moretlwe stated that:
This new analysis by Drolet and colleagues provides compelling evidence for HPV vaccine efficacy on all outcomes explored and for almost all age strata, and confirms their previous analysis. It also confirms a greater and faster direct impact and herd effects in countries with multiple age-cohort vaccination and high vaccination coverage, compared with countries with single age cohort vaccination or low vaccination coverage.
I have presented in this article four published, peer-reviewed, high-quality articles that establish firm evidence supporting Gardasil vaccine effectiveness. These are not unpublished junk science that does nothing but scare parents and individuals from protecting themselves from dangerous cancers.
I only chose four of the best articles, but there are many others that say the same thing – the HPV vaccine prevents cancer. Again, there are so few ways to prevent cancer, why wouldn’t you take the vaccine that can actually prevent cancer?
- de Sanjose S, Delany-Moretlwe S. HPV vaccines can be the hallmark of cancer prevention. Lancet. 2019 Jun 26;. doi: 10.1016/S0140-6736(19)30549-5. [Epub ahead of print] PubMed PMID: 31255298.
- Drolet M, Bénard É, Pérez N, Brisson M. Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis. Lancet. 2019 Jun 26;. doi: 10.1016/S0140-6736(19)30298-3. [Epub ahead of print] PubMed PMID: 31255301.
- Kjaer SK, Nygård M, Sundström K, Dillner J, Tryggvadottir L, Munk C, Berger S, Enerly E, Hortlund M, Ágústsson ÁI, Bjelkenkrantz K, Fridrich K, Guðmundsdóttir I, Sørbye SW, Bautista O, Group T, Luxembourg A, Marshall JB, Radley D, Yang YS, Badshah C, Saah A. Final analysis of a 14-year long-term follow-up study of the effectiveness and immunogenicity of the quadrivalent human papillomavirus vaccine in women from four Nordic countries. EClinicalMedicine. 2020 Jun 20;23:100401. doi: 10.1016/j.eclinm.2020.100401. PMID: 32637895; PMCID: PMC7329692.
- Lei J, Ploner A, Elfström KM, Wang J, Roth A, Fang F, Sundström K, Dillner J, Sparén P. HPV Vaccination and the Risk of Invasive Cervical Cancer. N Engl J Med. 2020 Oct 1;383(14):1340-1348. doi: 10.1056/NEJMoa1917338. PMID: 32997908.
- Lukács A, Máté Z, Farkas N, Mikó A, Tenk J, Hegyi P, Németh B, Czumbel LM, Wuttapon S, Kiss I, Gyöngyi Z, Varga G, Rumbus Z, Szabó A. The quadrivalent HPV vaccine is protective against genital warts: a meta-analysis. BMC Public Health. 2020 May 28;20(1):691. doi: 10.1186/s12889-020-08753-y. PMID: 32460747; PMCID: PMC7254696.
- Van Dyne EA, Henley SJ, Saraiya M, Thomas CC, Markowitz LE, Benard VB. Trends in Human Papillomavirus-Associated Cancers – United States, 1999-2015. MMWR Morb Mortal Wkly Rep. 2018 Aug 24;67(33):918-924. doi: 10.15585/mmwr.mm6733a2. PubMed PMID: 30138307.