Concerns about a paper on HPV vaccination and pregnancy rates

A short post based on a Twitter thread I wrote today about a paper I had seen a while ago. You can also read the ThreadReaderApp post, which many people find easier to read.

A couple of weesk ago, I saw a social media post claiming that the HPV vaccine would cause infertility in women, based on results in a peer-reviewed paper. It sounded hard to believe, because many other studies have found that the HPV vaccine is safe to use. There was no time that day to look up the details and I let it go.

Yesterday, I talked to a friend about HPV vaccination, and I remembered – and found – the HPV vaccine/infertility paper again. Here is the paper, published in a Taylor & Francis journal:

• A lowered probability of pregnancy in females in the USA aged 25–29 who received a human papillomavirus vaccine injection – Gayle DeLong – Journal of Toxicology and Environmental Health, Part A 81(14):661-674, 2018

HPV types, screening, and vaccination

Here is some background about the HPV vaccine. “HPV” stands for human papillomavirus, which is a group of viruses that can be transferred from one person to another during sex. HPV infections are very common among sexually active persons, usually do not cause any symptoms, and disappear by themselves. However, in some cases, the body does not clear up the infection, and these long-lasting infections can cause disease. Different HPV strains are associated with different types of symptoms. Certain HPV types can cause genital warts, while other types (types 16 and 18 in particular) are associated with cervical, anal, and several other types of cancer. The HPV vaccine is specifically designed to prevent infections with these cancer-associated virus strains. It is basically a vaccine that can prevent certain types of cancer, and thus can save lives.

Most women over 21 with access to healthcare will be familiar with the “Pap” test, in which some tissue is taken from the cervix and examined for the presence of pre- or cancerous cells. This exam is usually performed every 3 years, and can detect early stages of cervical cancer. For women over 30, new US guidelines recommend a Pap test plus HPV detection every 5 years.

The HPV vaccine is relatively new (released around 2006) and it is recommended for girls and boys age 11-12, before teenagers become sexually active and can acquire – or spread – the infection. You can read more about the current CDC recommendation regarding HPV vaccination here.

The HPV vaccine is safe and does not negatively affect pregnancy rates

The HPV vaccine has proven to be very safe (see for example here and here) so it was strange to see a paper claiming it would reduce pregnancy rates. That would be horrible!

The claim made in the DeLong paper also appeared to contradict results from a large 2017 study on 3500 women trying to become pregnant. This study found that HPV vaccination status had no negative effect on pregnancy probability. In fact, the researchers found that prior HPV vaccination in women with a history of sexually transmitted infections actually increased their chances of becoming pregnant.

Hat tip for finding this study: Alison Gemmill through Twitter.

A first look at the DeLong paper

Here is a screenshot of the abstract. Reading it, you might assume that the sole author analyzed data from 8 US million women, and you might think “wow, that is a big study”. But digging a bit deeper in the abstract reveals that the study looked at survey results from only 700 women, so much smaller than the abstract suggests.

For her study, DeLong used responses to the National Health and Nutrition Examination Survey (NHANES). She first shows this graph of declining pregnancy rates in women between 25-29 years old. This seems plausible. Women have babies at a later average age than a decade ago.

The sample set of the 700 women surveyed between 2007 and 2014 included 118 women who got the HPV shot and 582 who did not. This also makes sense because the vaccine was only introduced around 2006. The vaccine is typically given to young teenage girls so if you interviewed women aged 25-29 between 2007-2014, most of them did not get the vaccine because it was not being offered to them.

Here is a look at the demographics between vaccinated and un-vaccinated women (Table 2). There are some interesting statistical differences between these 2 groups, marked here by me in red.

Higher % college degrees in the HPV-vaccinated group

There is one very important difference between the 2 groups that were compared in this study. The women who had an HPV shot had a significantly higher chance of having a college degree. There was also a trend (albeit not significant) that they had a higher family income. 

There are several plausible explanations for the higher rates of HPV vaccination among women with a college degree. Higher educated women might know more about the benefits of the vaccine, or might have better access to healthcare, than women without a college degree or of lower-income families. We could even jokingly argue that getting the HPV vaccine might increase one’s collage application chances.

As a side note, the surveyed women appeared to be only 2.25 feet (67 cm) tall (highlighted in blue) 😂 But @ThatsRegretTab1 quickly pointed out that this looked like a duplication of the data in the “age” row.

Correlation between education levels and age of giving birth

This difference in % college degrees and family income between the 2 groups could be a HUGE confounding factor in pregnancy rates in young women. Here is why.

Take a look at this graph, published in the New York Times about a year ago. It shows that women with college degrees, on average, have their first baby at a later age than women without a college degree.

Women with a college degree or higher are on average 30.3 years old when they have their first baby. So if you interview women who are 25-29 old and ask if they ever had been pregnant, that means you are leaving out women who did not have their first baby YET.

A much better study design would have been to include women up to 35 or 40 years old, so you are also including the women who had their babies at a slightly later age.

The way the author chose the age group to be limited to young women, together with the significant difference in % college degrees between vaccinated vs. unvaccinated women suggests this is a very biased, non-scientific study.

Other critical reviews of the DeLong paper

Here are some other critical blog posts about this study that bring up other flaws in DeLong’s study.

• A dumpster fire of a study about HPV vaccination and female fertility, courtesy of Gayle Delong – Orac aka @gorskon – Respectful Insolence
• HPV vaccine affects pregnancy rate – laughable anti-vaxxer study – Skeptical Raptor
• Gayle DeLong tries to correct her anti-vaccine article by blogging – Skeptical Raptor

Points raised in these posts are the following:

• DeLong is a well-known antivaxer, someone who claims that vaccines cause autism.
• Although she is an associate professor of economics and finance, she has no background in science, epidemiology, or medicine.
• The study failed to report the rates of contraception in either vaccination group. Contraception is obviously another important confounding factor in the changes of becoming pregnant, but the paper does not report the answers to questions about contraception, even though they were included in the survey data that was used.
• Although DeLong claims that the vaccine is negatively affecting birth rates, she did not find the dose-response relationship that one would expect if the vaccine was toxic.

Conclusion

• The study’s claim that HPV vaccination inhibits the chances of becoming pregnant are incorrect, because the author only included young women, and ignored the fact that many women have their first baby only after turning 30. The author ignored the important confounding factor of having a college degree, which was significantly higher in the vaccinated group. By not including women 30 years or older, she biased the results of her survey to ignore the fact that HPV vaccination status, college degree, and age of first pregnancy are intricately connected.
• You can read my concerns about this paper in this PubPeer post.
• I would love to see a similar analysis done on a larger group and that included women up to 40 years old, and the answers to contraceptives use.