It’s Way Too Early to Say IUDs Reduce the Risk of Cervical Cancer

“Invasive cervical cancer may be approximately one third less frequent in women who have used an IUD.” That’s the conclusion from a systematic review published this week in the journal Obstetrics and Gynecology.

Many outlets have reported on the findings, but some coverage of it takes it too far: intrauterine devices (IUDs) “may cut risk of cervical cancer,” The Guardian claimed. The contraceptive “may reduce a woman’s risk,” CBS News wrote. Others touted the lower risk as a “surprising benefit.” The study only found an association between IUDs and lower rates of cervical cancer, not that IUDs caused women’s risks to drop. IUDs are awesome—they’re more than 99 percent effective at preventing pregnancy for as long as ten years and having one means you don’t need to remember to take a pill at the same time every day—but let’s not get overexcited here. To really understand what the study’s findings mean for women, we need to look at the details.

For the meta-analysis, researchers gathered all the papers on IUDs and cervical cancer that had been published through 2016. In their final review, they included data on more than 12,000 women from 16 studies, which were all conducted in the 80s and 90s, except for one, which ran until 2006. The authors found that rates of cervical cancer were a third lower in women with IUDs than women without them.

Hold the applause. The timing of the studies has several implications. “In the 80s and 90s, women did not have access to hormonal [IUDs],” says study author Victoria Cortessis, an assistant professor of clinical preventive medicine at the University of Southern California. That means only copper IUDs were included in the data, so there’s no way to know if hormonal IUDs—like Mirena and Skyla—might be associated with similar patterns, she says. There was also no HPV vaccine back then (Gardasil was first approved in 2006), and most importantly, IUDs weren’t marketed or intended for women with multiple sex partners or a history of STIs.

But number of sex partners is the most powerful predictor of HPV infection, the virus which causes roughly 90 percent of cervical cancers. That means it’s likely that the women in these studies who had IUDs already had a lower chance of contracting HPV (and developing cervical cancer) to begin with, while the women without IUDs may have been at greater risk because of their sex lives.

“These are known risk factors for cervical cancer that aren’t accounted for,” says Josh Kesterson, the chief of the division of gynecologic oncology at Penn State Health Milton S. Hershey Medical Center, adding that other things like HPV status, access to screening, and age at first sexual intercourse also affect your risk. (All the studies controlled for women’s age, but it was a mixed bag for all the other risk factors.) “This review has many variables which are unaccounted for and many unknowns,” he says.

Seven of the 16 studies in the meta-analysis actually came from a single paper, which wasn’t a randomized control trial but rather an analysis of other studies. Many also relied on patient interviews—not a very reliable method for gathering accurate information.

“You have to think about the biases that come with that and how we remember things and how that might be different among cancer patients and non-cancer patients,” says Kimberly Levinson, an assistant professor at Johns Hopkins University and the associate director of gynecologic oncology at the Greater Baltimore Medical Center. “I think we do have to consider the biases of each of the studies and recognize that we have an HPV vaccine, which is a known preventive measure for this disease.”

The authors propose three ways that IUDs may reduce a woman’s risk—if they do, and it’s not just an association. First, a quick lesson on cervical cancer: Some high-risk HPV types, like types 16 and 18, are invasive enough that they can hijack certain cells and convert them from normal cells to dysplastic, or precancerous, cells. These HPVs are especially dangerous in the so-called transformation zone. That may sound like something out of a sci-fi movie, but it’s simply a spot at the opening of the cervix where abnormal cells are most likely to develop. “It’s an area where columnar cells are now exposed to the acidic pH of the vagina and turn into a squamous cell type,” Kesterson explains. “If the HPV hijacks those metaplastic cells at that time, you can appreciate that it probably has a more aggressive effect.” These cells are more susceptible to HPV infection and dysplasia.

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One hypothesis on how IUDs might help is that the tissue in the transformation zone might get bruised and injured when the device is placed. “That may evoke an immune response in the short term that would clear a persistent infection that’s already there,” Cortessis says. That kind of immune response would cause a flood of granulocyte cells to the area. “They may recognize the virus as being something foreign and then mount a specific immune response to clear the persistent infection,” she adds.

Kesterson is skeptical about this potential mechanism, since there’s no data to support it. “Do we know that HPV is a virus, thus you could think of cervical cancer ultimately as a communicable, transmittable disease, like an infectious disease? Sure,” he says. “Does your immune system come into play with that? Sure. But I don’t know that you can make a statement about the etiology of a one-time trauma to the cervix with an IUD insertion preventing cervical cancer.”

It could also be that a woman’s body launches an immune response against the IUD itself because it recognizes it as a foreign object, Cortessis says. In this case, the immune cells could attack the virus in a similar way. Their third and final hypothesis poses that precancerous cells could be scraped away when the device is removed, though Cortessis admits that’s more of a stretch.

“We know that the immune system plays an important role in cervical cancer and that there are immune reactions at the local level of the cervix,” Levinson says. “The immune system can take care of cervical dysplasia and cause regression of disease, but how those things are affected by IUD placement is something that I think requires further investigation.”

The best way to define a true link between IUDs and a reduced risk of cervical cancer would be to conduct a randomized control trial that compares women with and without IUDs today—and control for whether they’d had the HPV vaccine. If research that follows women over time does find that IUDs have a non-contraceptive benefit, then we’d want to find out how, Cortessis says. Until then, IUDs shouldn’t act as a replacement for regular screening like Pap smears or getting the vaccine. “We certainly don’t want to give the impression that using an IUD would be any kind of substitute for screening,” she says. “That’s the intervention that’s going to be protecting women for years to come.”

The authors note that in low-resource countries, less than two percent of girls receive one or more doses of the three-dose HPV vaccine. There’s a “growing need for approaches to cervical cancer prevention that can be widely used by HPV-exposed women in low-resource settings,” they write.

But here’s the thing. “The problem with low-resource environments is that they’re low-resource environments, so they don’t have IUDs, or access to care, or gynecologists placing those things,” Kesterson says. “If you want to give someone access to care, do a Pap smear, give them a vaccine. There are many ways to help the underserved, but I don’t think an IUD can be administered with any kind of clinical evidence that says, yes, it may reduce the risks of cervical cancer.”

The fact remains that very few girls and women in developing countries have access to the HPV vaccine or to screening. Cortessis and her colleagues decided to explore whether IUDs affect cervical cancer risk because, until these measures are widely available, we need to find ways to reduce a woman’s risk after she’s already been exposed to HPV. “We know that women are not properly screened and we want them to have any benefit we can find that other modalities might bring them,” she says.

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