HPV vaccine prevents cervical cancer – a systematic review

One of the many tropes about HPV vaccine from the anti-vaccine religion is that the vaccine has no effect on any cancer. Recently, I wrote an article that outlined the evidence that supports a link between HPV vaccines and cancer – that is, the vaccine does lower the risk of cancer. After I wrote that article, a new systematic review was published that, indeed, the HPV vaccine prevents cervical cancer.

Many people think that cancer is some sort of on/off switch – in fact, HPV-related cancers may take years or decades to be diagnosed. However, it’s been 8-12 years since the vaccine has been available (depending on the country), so a population of young women (the vaccine was only indicated for women in most countries until a few years ago) is now getting to the age where they may be diagnosed with either cancer or pre-cancerous lesions.

As the population of women (and eventually men) reaches the age where risks of certain cancers are increased, we can use epidemiological studies to determine whether or not there is a difference in cancer risk between vaccinated and unvaccinated groups. Let’s review the systematic review that examined a surprisingly large number of studies that support the fact that the HPV vaccine prevents cervical cancer.

All about HPV vaccines

Many of you have read this section an enormous number of times, however, for some of the readers of this blog, this article might be their first bit of research into the human papillomavirus (HPV) vaccine. I feel it is important to a new reader to review the facts behind the human papillomavirus, the HPV vaccines, and HPV-related cancers. This section is constantly updated for even regular readers, but you can skip ahead if you know all of this.

Genital and oral  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. 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:

These are all dangerous and disfiguring cancers that can be mostly prevented by the HPV cancer vaccine. If you’re a male, and you think that these are mostly female cancers, penile cancer can lead to amputation of your penis. Just think about that guys.

There is also some fairly strong evidence that HPV infections might be linked to prostate and some skin cancers, which would vastly increase the number of HPV-related cancers diagnosed every year. The HPV vaccine could be one of the best prevention tools for cancer we’ve ever found.

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 31,000 HPV-related cancers are diagnosed in the USA every year.

There were two HPV vaccines on the world market before 2014. GSK, also known as GlaxoSmithKline manufactured 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 deadly cancers that are related to HPV. It is definitely a cancer-preventing vaccine.

(Just a quick note. There are actually two cancer-preventing vaccines. Along with the HPV vaccines, the hepatitis B vaccine is also important for the prevention of some cancers.  The vaccine prevents hepatitis B viral infections. Chronic hepatitis B infections can lead to liver cirrhosis or cancer. Liver cancer is actually one of the few cancers in the USA where the incidence has increased over the past few years. And if you follow the anti-vaccine rhetoric, you know the hepatitis B vaccine is almost as controversial as the HPV vaccine.)

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.

 HPV vaccine prevents cervical cancer – systematic review

There have been boatloads of evidence that the HPV prevents HPV infections. There is even more evidence that the HPV is linked to many cancers, including recent evidence that it might be linked to some prostate and skin cancers. Yes, the evidence that the HPV vaccine prevents cervical cancer was circumstantial using transitive properties, but it’s fairly clear that if you stop HPV, you can stop HPV-related cancers. Logical, yes?

However, as more and more time passes since the first group of girls received the vaccine (from 2006-2011 depending on the country), that group would be in their 20s and would also be at increased risks of both cancer and pre-cancerous lesions. A large epidemiological study could identify any differences between vaccinated and unvaccinated populations – and we can test the hypothesis of whether the HPV vaccine prevents cervical cancer.

Actually, there has already been an unexpected number of studies that have examined whether the vaccine prevents cervical cancer. And that’s when a systematic review, which collects and analyzes data from numerous studies while removing bias and other issues, which can roll up all of the data from each of those studies, and give us even more powerful data. And as I’ve stated many times, systematic reviews are at the pinnacle of the hierarchy of biomedical research – they represent the fundamental basis of science-based medicine.

HPV vaccine prevents cervical cancer – results

In this review, published in the Cochrane Database of Systematic Reviews (see Note 1), the authors included 26 different clinical studies with over 73,000 participants. The researchers searched several databases of clinical trials to find randomized clinical trials that compared safety and efficacy in females offered HPV vaccines with a placebo group (that usually included vaccine adjuvants).

To cut to the chase, the researchers found that the HPV vaccine reduced the risk of these cervical pre-cancerous lesions, which are associated with HPV16 or HPV 18, from 341 to 157 for every 10,000 women. HPV vaccination also reduced the risk of any pre-cancerous lesion from 559 to 391 per 10,000 in this group. Essentially, the researchers found significant reductions in the incidence of cervical intraepithelial neoplasia (which can be a precursor of cervical cancer).

Furthermore, the researchers reported that:

The risk of serious adverse events is similar between control and HPV vaccines in women of all ages (669 versus 656/10,000, RR 0.98 (0.92 to 1.05), high certainty). Mortality was 11/10,000 in control groups compared with 14/10,000 (9 to 22) with HPV vaccine (RR 1.29 [0.85 to 1.98]; low certainty).

Since these kinds of scientific statements can be so carefully worded that it can be confusing, let me be clear – adverse events are the same between vaccinated and unvaccinated groups, something that we’ve seen in numerous studies. Furthermore, there were no individual adverse events that were statistically more frequent than in vaccinated than unvaccinated groups. Ultimately, there are no statistical differences in mortality rate between vaccinated and unvaccinated groups.

In other words, the researchers found that not only did the HPV vaccine reduce the overall risk of serious pre-cancerous lesions, it also found there was no difference in the incidence of adverse events between the vaccinated and unvaccinated groups. And to remind the reader, especially those that push that ridiculous trope that the HPV vaccine wasn’t tested in proper clinical trials, these data come from proper clinical trials.

Finally, the authors concluded:

There is high-certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and young women aged 15 to 26. The effect is higher for lesions associated with HPV16/18 than for lesions irrespective of HPV type. The effect is greater in those who are negative for hrHPV or HPV16/18 DNA at enrolment than those unselected for HPV DNA status. There is moderate-certainty evidence that HPV vaccines reduce CIN2+ in older women who are HPV16/18 negative, but not when they are unselected by HPV DNA status.

I know that someone is going to complain that “this is only pre-cancerous lesion data” – true enough, but as the authors stated, these data are only for about eight years post-release of the vaccines, probably too early for cancers. However, pre-cancerous lesions lead to cancer. A reduction in these lesions leads to a reduction in cancer.

What too many people casually is the fear that a woman (and her family) have when they have a diagnosis of a CIN2+ or 3+ lesion – a painful procedure is required to remove the cancerous cells. Moreover, there is an increased risk of infertility or other damage as a result of this treatment.

Too many times I read, “women can get a pap smear, they don’t need the HPV vaccine.” Wrong, wrong, wrong. Getting a diagnosis of the more severe types of lesions means serious treatment options – getting the HPV vaccine demonstrably shows that risk of those diagnoses is substantially decreased.

Summary

Let me make this simple – this systematic review represents explicit and statistically significant evidence that the HPV vaccine prevents pre-cancerous cervical lesions, which require a painful medical procedure. And this is powerful evidence that clearly the HPV vaccine prevents cervical cancer.

This review also gives more substantial evidence that the HPV vaccine is incredibly safe, showing no difference in adverse effects between vaccinated and unvaccinated groups.

I tire of the myths that are propagated by the anti-vaccine zealots about the HPV vaccine. They are all demonstrably untrue – the vaccine does prevent HPV infections, the vaccine does prevent cancer, and the vaccine is incredibly safe.

So I ask once again – why doesn’t every parent in every country that has the HPV vaccine not get their children (or themselves) vaccinated? As I’ve said before, there really are only a few ways to prevent cancer, and the HPV vaccine prevents a large number of dangerous and disfiguring cancers.

Get the vaccine – it really can save lives.

Notes

  1. The Cochrane Database is considered one of the premier organizations that perform systematic and meta-reviews in the biomedical sciences. If I am looking to determine if there is evidence supporting a medical claim, I look here first. Now, I’m a scientist, so I don’t take their conclusions at face value – they have made egregious errors in systematic reviews of acupuncture quackery in the past. But like all scientific literature, one must examine a systematic review (whether published in Cochrane or any other journal) with a critical eye. Is there bias in including or excluding data? Do they overstate the conclusion? Do they rely upon unusual or bad statistical analyses?

Citations



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The Original Skeptical Raptor
Chief Executive Officer at SkepticalRaptor
Lifetime lover of science, especially biomedical research. Spent years in academics, business development, research, and traveling the world shilling for Big Pharma. I love sports, mostly college basketball and football, hockey, and baseball. I enjoy great food and intelligent conversation. And a delicious morning coffee!