HPV vaccination works. Period.

Of all the vaccines out there, the one that antivaxers tend to go the absolute most batshit nuts about is the vaccine against the human papilloma virus (HPV), of which there are two, Gardasil and Cervarix. There have been films portraying the vaccine as killing teenaged girls. Antivaxers spread stories of young women who died suddenly and try to blame Gardasil, whether Gardasil had anything to do with these tragic deaths or not. Now that more boys are getting the vaccine, they’re now doing the same thing using the deaths of teenaged boys. They also publish dubious studies claiming that the HPV vaccine causes premature ovarian insufficiently/failure and infertility.

Why the hate? I’ve speculated about this from time to time, and it always comes down to one answer: Sex. It’s the same reason why vaccinating neonates against hepatitis B also gets antivaccine activists so riled up. These vaccines tend to be demonized because of moralistic associations with sexual activity, given that HPV is most commonly spread by sexual activity and hepatitis is similarly often spread through bodily fluids exchanged during sex. This leads to what I’ve referred to as “slut-shaming” the HPV vaccine, given that it is recommended to be given before girls become sexually active by inferring (and sometimes more than inferring) that the HPV vaccine will encourage promiscuity by removing one of the consequences. As I’ve said before, that is one of the stupidest arguments against the HPV in existence. (Seriously, does anyone think teens worry about maybe getting cancer 20-30 years down the road when their hormones are raging right now?) As far as the hepatitis B vaccine, the rants usually come in the form of complaints questioning why it is given right after birth when a major mode of hepatitis B transmission is through sex, even though there are good reasons to administer the first dose of the hepatitis B when babies are neonates.

Of course, it’s not just about sex. It’s about the HPV vaccine being a cancer vaccine. We know the strains of HPV vaccinated against cause cervical cancer decades after infection and that two serotypes of HPV are responsible for 70% of cervical cancer cases, and approximately 90% of all cervical cancer cases are probably caused by HPV. It is therefore very reasonable to infer that preventing HPV infection by vaccinating girls before they become sexually active will prevent cervical cancer. Of course, because it takes decades after HPV infection for cancer to appear and widespread vaccination with HPV only started a little more than a decade ago. Of course, it’s useful to note that there are more than 150 strains or subtypes of HPV that can infect humans but that only 40 of these strains have been linked to one or more different cancers. Of those 40 strains, most are fairly rare. Even so, in poor countries, cervical cancer is a leading cause of female mortality, killing about 300,000 women a year.

Still, antivaxers can’t be pleased that yesterday there were news stories like this one in the New York Times:

Vaccines against the human papillomavirus have sharply reduced infections, genital and anal warts, and precancerous lesions in young women and girls in more than a dozen wealthy countries, a major new study has found — powerful evidence that these vaccines will ultimately cause major drops in cervical cancer. The vaccines are so effective that when given to enough young girls, they also give partial protection to both unvaccinated girls and boys, simply because fewer people in sexual networks are carrying the virus, commonly called HPV. The research, published on Thursday in The Lancet, analyzed dozens of studies that, when combined, included 66 million females and males below the age of 30 living in 14 wealthy countries where HPV vaccines were introduced as early as 2007.

Whoa.

Of course, it’s not all about sex. HPV vaccines are relatively new and there hasn’t been time to verify that the efficacy of these vaccines in decreasing surrogate outcomes (HPV infection) translates to less HPV-induced cancer, Well, antivaxers, read’em and weep. Actually, read it and weep. The aforementioned study the The Lancet is some serious evidence that HPV vaccination is going to be a major tool to reduce mortality from HPV-induced cancers. The title of the article is Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis. It is a paper by Mélanie Drolet et al and the HPV Vaccination Impact Study Group, which consists of researchers in Canada, the United States, Australia and Europe . It is, as its title suggests, an updated review and meta-analysis of article examining the efficacy of HPV vaccination. The original review and meta-analysis was published in 2015, and it showed substantial decreases in HPV 16 and 18 infections and anogenital wart diagnoses among girls and young women targeted for vaccination and in countries with high vaccination coverage (more than 50%) evidence of vaccine cross-protection and herd effects, with significant reductions in HPV 31, 33, and 45 infections among girls targeted for vaccination and anogenital wart diagnoses among unvaccinated boys and older women.

The authors wanted to update it for the following reasons:

We wanted to update our systematic review and meta-analysis for three main reasons. First, the number of countries and studies reporting observational data of the population-level impact of HPV vaccination has increased dramatically since our first review, which will improve both the power and generalisability of the results. Second, the number of years after vaccination has increased, which allows analysis of changes in CIN2+ since the introduction of HPV vaccination. Finally, the WHO Strategic Advisory Group of Experts on Immunization revised its position in 2016 to recommend HPV vaccination of multiple age cohorts of girls (9–14 years old) when the vaccine is introduced in a country, rather than vaccination of a single age cohort. Before this recommendation, some high-income countries had implemented vaccination of multiple age cohorts, mainly through catch-up campaigns. A better understanding of the population-level impact of will help inform decisions of policy makers regarding the recent WHO recommendations. Thus, the aims of this systematic review and meta-analysis are to: (1) update and summarise the most recent evidence about the population-level impact of girls-only HPV vaccination on HPV infections and anogenital wart diagnoses among girls, boys, women, and men; (2) summarise new evidence about the population-level impact of girls-only HPV vaccination on CIN2+ occurrence among screened girls and women; and (3) compare the population-level impact of HPV vaccination on anogenital wart diagnoses and CIN2+ occurrence between countries that have implemented either a single or a multiple age-cohort vaccination strategy.

Here’s what the authors did:

To update our first systematic review (of studies published between Jan 1, 2007, and Feb 28, 2014), we searched MEDLINE and Embase for studies published between Feb 1, 2014, and Oct 11, 2018, with the same combination of MeSH terms, title, or abstract words: (“papillomavirus vaccine”, “papillomavirus vaccination”, “HPV vaccine”, or “HPV vaccination”) and (“program evaluation”, “population surveillance”, “sentinel surveillance”, “incidence”, or prevalence”), and (“papillomavirus infection”, “condylomata acuminata”, “anogenital warts”, “cervical intraepithelial neoplasia”, “cervical dysplasia”, “uterine cervical neoplasm”, or “HPV related diseases”) (appendix p 6). ÉB or NP and MD independently identified eligible articles on title and abstract first, and then on the full text. Disagreement between reviewers was solved by discussion between those authors. Finally, we searched the reference lists of selected articles.

The authors identified 1,702 potentially eligible articles, and included 65 articles from 40 studies, 23 for HPV infection, 29 for anogenital warts, and 13 for CIN2+ (cervical neoplasia grade 2+). All studies were of sufficiently high methodological quality to be included in the meta-analysis; no studies were found with risk of serious bias. In countries where the vaccine has been distributed for more than five years, the two strains of HPV causing 70% of cancers (HPV 16 and 18) decreased by 83% among teenage girls and 66% among women between 20 and 24 years old. Even better, anal and genital warts decreased by 67% among teenage girls, by 54% among women from age 20 to 24, and by 31% among women from 25 to 29. Warts also decreased by half among teenaged boys and by a third in young men up to age 24.

In other words, HPV vaccination works. This analysis provides compelling evidence for the efficacy of HPV vaccination on every outcome examined and for nearly all age groups. It also confirms herd effects. What do I mean by that? Simple. There was significant evidence of a decrease in anogenital warts among boys and men in countries with girls-only HPV vaccination. Basically, because the pool of girls with HPV infection is decreased by vaccination programs targeting HPV, fewer boys are infected.

The authors also note:

Importantly, we also present the first pooled estimates of the population-level impact of HPV vaccination on CIN2+, which is the most proximal outcome to cervical cancer and is recognised as a valid proxy for vaccine efficacy against cervical cancer by regulatory agencies worldwide. The 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. The results can also inform potential changes to cervical screening programmes. Substantial declines in high-risk HPV types and CIN2+ might allow for screening to start at an older age and for longer screening intervals. However, when considering any changes in screening recommendations, careful attention will have to be given to unvaccinated cohorts of women. The decreasing HPV prevalence observed in several settings also support a switch from cytology alone to primary HPV testing followed by cytology triage in younger and older cohorts, to benefit from the higher sensitivity of HPV testing to detect pre-cancerous lesions and higher specificity of cytology, without substantially increasing the number of false positive results.

In other words, there has been an effect on the the prevalence of the lesion farthest along the pathway to cervical cancer. HPV vaccination works. All evidence to this point strongly supports the conclusion that it prevents HPV-caused cancers, the most prominent of which is cervical cancer. Antivaxers can claim otherwise, but science does not support them. HPV vaccination works.