Although I have no poll numbers sitting in front of me, and certainly no scientific peer-reviewed research, I just have a feeling that if you scratch the surface of an anti-vaccine activist, you will find that if they could hate one vaccine, it would be Gardasil. And one of the arguments will be all about Gardasil effectiveness – they claim it doesn't actually prevent cancer.
When you couple their false claims about the dangers of the vaccine with the claims about the lack of Gardasil effectiveness, you'd probably agree with the anti-vaccine crowd. Despite these false claims, HPV vaccine uptake has slowly grown in the US and other countries.
I've written nearly 200 articles about the HPV cancer-preventing vaccine, but most of those are focused on debunking myths and confirming the safety of the vaccine. I'm going to focus on a quick primer about Gardasil effectiveness in preventing cancer. Stay tuned for some interesting science.
All about HPV vaccines
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 strain, 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 31,500 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 31,500 cancers a year in the USA alone. The HPV vaccine prevents becoming infected by HPV, which means you are protected from these cancers.
HPV and cancer
Research published in Cancer and the Journal of the National Cancer Institute reviewed cancer statistics and pathology which formed the basis of the chart above. You can quickly see the number of HPV-related cancers by cancer and by subtype of HPV in the USA every year. According to this research, there are about 31,500 new cancers every year that are linked to HPV.
Of those new HPV-related cancers, 29,100 are caused by HPV subtypes that are blocked by the relatively new Gardasil9 vaccine. I know, many of you are going to look at that 29,100 and think, "well, that's not that many people."
I think one of the myths about cancer is that it's a raging epidemic and half the world is afflicted by one cancer or another. But most cancers are quite rare, and most have unknown etiologies. However, we know that the seven cancers listed in the chart above are most likely caused by HPV. These HPV-related cancers, if grouped together, would be ranked in the top 20 list of cancers across the world.
Sure, the most common cancers, like lung, breast, prostate, and colon, are substantially more common than HPV-related cancers. But, other than lung cancer and smoking, these other cancers cannot be prevented by anything known today – certainly not as easy as getting an HPV vaccine.
Cervical cancer and HPV
Gardasil was initially developed to prevent cervical cancer, but, as we have seen, it is useful for preventing at least six other cancers too. But I thought I would focus on cervical cancer since it shows us the evidence that HPV actually causes cancer.
As I wrote above, HPV is linked to numerous cancers (including some not listed such as, potentially, skin cancer). How do we know this? Because we've studied the pathology of several cancers, including cervical, and have found that the human papillomavirus has transformed the cell in ways that make it cancerous.
A systematic review (considered the pinnacle of the hierarchy of scientific research) of cervical cancer concluded that "most SCNC and LCNC (small-cell and large-cell neuroendocrine cancers of the cervix) are caused by HPV, primarily HPV18 and HPV16. Therefore, most if not all SCNC and LCNC will be prevented by currently available prophylactic HPV vaccines."
Another study states that "Cervical cancer is initiated by high-risk types of the human papillomavirus (hrHPV) and develops via precursor stages, called cervical intraepithelial neoplasia (CIN)."
The science supporting a causal link between HPV infections and various types of cervical cancer is clear. The scientific consensus supports this link, and dismissing it out of hand is not supported by the evidence.
Not all cervical cancers are caused by HPV (although, as we saw in the chart above, about 90% are). Not all HPV infections in women cause cervical cancer, most HPV infections resolve themselves.
As we see in the chart in the previous section, the number of new HPV-related cervical cancers cases each year in the USA is relatively small – about 10,600. But 4,115 women died in 2014 from this cancer.
Given the powerful evidence that HPV is linked to cervical cancer, and it kills about a third of the women who contract it, it seems logical that preventing the HPV infection in the first place is a good thing. The argument from the anti-vaccine world is that it's "only" 4,000 deaths and only 11,000 new cases. I don't understand why the anti-vaccine world dismisses 4,000 deaths as if it is not relevant.
The other issue is that the time period from infection to diagnoses of cancer can be decades. Many people cannot imagine that some infection that they get in their 20s has something to do with cancer 30 years later. But it may not actually be that infection – remember some of the HPV subtypes are so common, each of us might get re-infected several times in our life, especially if we have more than one or two sexual partners. In addition, the course of many cancers takes a significant amount of time.
Most cancers are relatively rare, but there's no known way to prevent most of them. And here we have a very safe (despite the claims of the anti-vaccine world) vaccine that will prevent one deadly cancer.
Gardasil effectiveness against HPV infections
Unless someone has a serious amount of evidence against the link between several HPV subtypes and those seven cancers, we can move on. We know that HPV is causal to at least seven cancer – now, we need to determine if the HPV vaccines are effective at preventing HPV vaccines. And the evidence to support Gardasil effectiveness is robust and overwhelming.
A large systematic review (and let me remind the reader once again, systematic reviews are the gold standard of biomedical research) of Gardasil effectiveness studies found that the HPV vaccines are highly effective in preventing the transmission and spread of many HPV subtypes:
Although HPV models differ in structure, data used for calibration, and settings, our population-level predictions were generally concordant and suggest that strong herd effects are expected from vaccinating girls only, even with coverage as low as 20%. Elimination of HPV 16, 18, 6, and 11 is possible if 80% coverage in girls and boys is reached and if high vaccine efficacy is maintained over time.
Of course, I'm troubled by a herd effect from only 20% coverage (and in the USA, HPV vaccine uptake is around 60%) – but the researcher's analysis seems solid. But if we can get 80% coverage, we might eliminate the four most common HPV subtypes. That would be amazing, allowing a generation of teens and young adults to not worry about the cancers that afflict humans today.
In another study I analyzed, the researchers observed that the oral HPV infection rates in the vaccinated group were about 88% lower than those individuals who were not vaccinated. Moreover, the investigators actually found no infections in vaccinated males, which would suggest that Gardasil may reduce the prevalence of those infections by as high as 100%. HPV-related head and neck cancers disproportionately affect males, so this data may be important in increasing Gardasil vaccination rates in males.
Another study, published in Pediatrics (and reviewed by me), by Dr. Lauri Markowitz and her colleagues, provided strong evidence that the HPV vaccination schedule is directly linked to a reduction in HPV infections.
Dr. Markowitz investigated the rates of HPV infection among teens in the USA after the introduction of the HPV vaccine. She found that the infection rate, in teens aged 14 to 19, dropped by 64% in the six years after the vaccine was added to the recommended vaccination schedule. Furthermore, the infection rate dropped by34% among people ages 20 to 24.
In case you’re asking, there is simply no evidence that the decline was caused by a sudden nationwide teen celibacy increase. Of course, there is just no link between sexuality and the HPV vaccine, so there’s that.
One of the "criticisms" of Gardasil effectiveness is that we don't know how long the vaccine will work. So there's another study, published in Pediatrics, provides evidence that the effectiveness, measured by the immunity provided by the HPV vaccine, lasted at least 8 years. The study followed 1781 children, ages 9-15, for 8 years following vaccination with the HPV quadrivalent vaccine (about ⅔ of the group) or a placebo (about ⅓). At month 30, the placebo group received the vaccine.
The researchers determined the effectiveness of the vaccine by testing the participants’ blood for anti-HPV seropositivity (that is, an indication of antibodies to HPV in the blood). The results of the study provide more powerful evidence of the effectiveness of the vaccine. They concluded that vaccination-induced anti-HPV response was clinically detectable through month 96 (or 8 years).
Over time, we will get additional studies published that will check the long-term immune status of vaccinated individuals. Maybe in year 25, we notice a drop in immune status, and we could recommend a booster shot. That is how science works, it keeps gathering and analyzing data to revise original claims about the vaccine.
I could go on and on and on. There are over 800 published articles that discuss Gardasil effectiveness – almost all of them support the overall importance of the HPV vaccine in preventing cancers. (And yes, I'm sure some anti-vaccine activist will cherry pick some poorly designed article published in a predatory journal, and then claim that I'm wrong.)
Gardasil effectiveness – preventing cancer
I recently wrote about a systematic review, considered the pinnacle of the hierarchy of published biomedical research, which examined results from 26 different clinical studies with over 73,000 participants. The article, published in the Cochrane Database of Systematic Reviews(see Note 1), described how 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 cervical pre-cancerous lesions, which are linked to HPV16 or HPV 18, from 341 to 157 for every 10,000 women. The HPV vaccines also reduced the risk of any pre-cancerous lesions 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).
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” – fair enough. But as the authors stated, these data are only for about eight years post-release of the vaccines, probably too early for the detection of cancers. However, let's be clear – pre-cancerous lesions can lead to cancer. A reduction in these lesions leads to a reduction in cancer.
What too many people casually dismiss 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 damageas a result of this treatment. Preventing these lesions is a good thing.
In addition, 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.
More evidence of Gardasil effectiveness
Another recent article, by Fangjian Guo et al. and published in the American Journal of Preventative Medicine, reported that the cervical cancer rate for young women fell after the HPV vaccine was introduced in the USA. The vaccine was first introduced in 2006 in the USA, initially, just for females.
The researchers analyzed 2001-14 data on 15-34-year-old females from the CDC National Program for Cancer Registries (NPCR) and the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) programs which closely track cancer rates in the USA. Combined data from NPCR and the SEER Program include cancer incidence and population data for all 50 states, the District of Columbia, and Puerto Rico, providing information on more than 24 million cancer cases.
The results were impressive. The average annual cervical cancer rate, for women aged 15-24 years, dropped from 8.4 per million during 2003-06, before the vaccine was introduced, to 6.0 per million during 2011-14. This represents a statistically significant 29% reduction in the cervical cancer risk. The authors also reported that the rates fell for both squamous cell carcinoma of the cervix (SCC) and non-SCC, and there was a sharp decline after 2009.
The authors concluded that:
This study found a significant decrease in cervical cancer incidence among young females after HPV vaccine introduction. The observed strong decrease in cervical cancer incidence among young females aged 15–24 years is unlikely to result entirely from changes in cervical cancer screening, suggesting HPV vaccination is at least partially responsible for the reduction in cancer incidence. These findings serve as further evidence of the effectiveness of HPV vaccination in preventing cervical cancer.
This is important, because despite previous evidence of HPV vaccine effectiveness against HPV infections, genital warts, and cervical lesions, it is essential to know its effect on the target outcome, cervical cancer.
The TL;DR summary of Gardasil effectiveness
First, we have robust and nearly irrefutable evidence that several subtypes of HPV are causally linked several deadly cancers. Second, we have similarly strong evidence that HPV vaccines either reduce HPV infections which lead to tens of thousands of cases of new cancers. And third, there is powerful evidence that the HPV vaccine reduces the actual risk of cancer.
To make specious claims that the HPV vaccine somehow doesn't prevent cancer is typical vaccine denial – understate the benefits of vaccines and overstate the dangers (if there actually are any). It's terribly frustrating because there are children that can be protected against cancer.
Gardasil is demonstrably effective, as you have read above. It is demonstrably safe. Protect yourself and your loved ones from cancer – you'll thank me down the road.
Notes
- 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?
- Recently, researchers at another branch of Cochrane, known as Cochrane Nordic, who have shown a profound bias against the HPV vaccine, published an attack on this systematic review. Their criticisms are laughable and have been critically discussed elsewhere.
Citations
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