HPV is an odd little virus. It’s exclusive to humans (hence, human papillomavirus), it can manifest as annoying warts on the hands and feet, it can be present in the body with no symptoms at all, and… it’s largely responsible for the fourth most common cancer in women: cervical cancer. The fact that HPV causes cervical cancer might not be news, but we’re continuing to learn more about what increases the risk of HPV developing into cancer. Specifically, there is a link between hormonal birth control use, especially long term, and cervical cancer.
What is cervical cancer?
Cervical cancer is a type of cancer that begins on the cervix. The cervix is the passageway between the uterus and the vagina. Cancer is disease caused by cells that grow and replicate abnormally (tumors) and are able to invade other tissue and parts of the body (malignant tumors).
What’s the connection between cervical cancer and HPV?
According to the World Health Organization, 99% of cervical cancer cases are linked to prior HPV infection. HPV (human papillomavirus) refers to a large group of viruses, and while some strains cause warts, others cause no symptoms. Unfortunately, the strains that do not cause warts or other obvious symptoms, such as HPV-16 and HPV-18, are the ones most likely to lead to cancer. While most cases of HPV are cleared by the body’s immune system, a persistent infection can eventually lead to cancer.
This happens because HPV is a DNA virus, and it replicates by inserting its DNA directly into the DNA of the host cell to get the host cell (in this case, a cervical cell) to start producing copies of the virus. When the viral DNA exists alongside the host DNA for a long time without being destroyed by the immune system, the virus can contribute to the cell becoming cancerous. It does this by disrupting the host DNA itself and because proteins created by the virus’s DNA inhibit normal checks and balances the cell uses to avoid growing and replicating out of control [1].
Here’s why it’s difficult to identify non-HPV causes of cervical cancer
HPV is sexually transmitted and it’s the #1 most common sexually transmitted infection (STI) worldwide. Condoms are less likely to prevent HPV spread than other STIs because HPV can spread from infected skin or other areas that a condom can’t cover.
HPV is so common that the CDC reports that “most people” will be infected with HPV at some point, making it difficult to identify independent causes of cervical cancer. One known independent cause is exposure to diethylstilbestrol (DES), a synthetic form of estrogen, in utero. This exposure group only includes women born between the years of 1940 and 1971 whose mothers were prescribed this drug while pregnant. While DES has mostly fallen out of use, different forms of synthetic estrogen, as in hormonal birth control, are still commonly prescribed.
How is cervical cancer diagnosed?
Cervical cancer is usually screened for through a procedure called a Pap smear. During a Pap smear, a provider uses a small brush to collect cells from the cervix. These cells are then sent to a lab to screen for abnormalities. A provider may also test for high-risk HPV strains at the same time. If the results of a Pap test indicate that more investigation is needed, a doctor will likely collect a biopsy to make a proper diagnosis.
According to the CDC, 11,500 new cases of cervical cancer are diagnosed each year. There are 4,000 deaths each year in the US from cervical cancer [6]. Cervical cancer is rare before age 30. The most common age range for diagnosing cervical cancer is between 40 and 44 years old. Risk factors include smoking, having HIV, and having a high-risk strain of HPV (HPV-16 or HPV-18).
Can cervical cancer be cured?
Cervical cancer is a highly treatable cancer, especially in early stages. Like with other cancers, the first step is often to try to remove the cancer surgically. If the cancer has advanced, radiation and chemotherapy are often used together to destroy cancer cells. According to the CDC, the five-year survival rate for cervical cancer is 67%. But when the cancer is still localized (has not spread to other tissue) at the time of diagnosis, the five-year survival rate is 91%, highlighting the importance of early detection.
The connection between cervical cancer and hormonal birth control
In the past few years, several studies have explored the connection between hormonal birth control use and the risk of developing cervical cancer. A 2020 study of over 1.8 million women in Denmark, their birth control status, and development of cervical cancer through the Danish Sex Hormone Register, found that the relative risk of ever-users of hormonal birth control was 1.19 compared to non-users [2]. This means that cervical cancer was diagnosed about 19% more often in women who had used birth control at any point compared to women who had never used birth control.
The researchers also found that the risk was higher for women who had used birth control for longer periods of time and for women prescribed contraception at higher doses.They also found that the risk decreased after being off of birth control for a long time, returning to a baseline risk after ten years post-discontinuation [2].
A 2020 population study of 80,000 Dutch women found that using birth control for more than five years was associated with twice the chance of developing cervical cancer compared to non-users [3].
A systematic review published in 2020 compiled the findings of 19 studies. The reviewers found that oral contraceptive use was commonly associated with increased risk of cervical cancer development, with this risk ranging from a 24% to 32% increase compared to non-users. The risk was greater the longer oral contraceptives were used [4].
How birth control might make the cervix more susceptible to cancer
During my research into cancer biology, I learned that most studies tend to focus on whether or not there is a connection between contraception and cervical cancer. There is no clear answer yet as to why there’s a link. However, we can use what we know about cervical cancer and birth control’s effects upon the cervix to speculate.
For starters, we know that cervical cancer is virtually always connected to HPV. We also know that birth control impacts the immune system and how the cervix normally protects itself from infection. Prolonged hormonal contraception use alters and shrinks the cervical crypts, preventing the cervix from producing the cervical mucus that self-protects against infection. Furthermore, hormonal birth control (HBC) is known to impact the epithelial (outer cell layer) development of the cervix, which is necessary for the cervix’s ability to resist infection. HBC everts or turns ‘inside out’ the tissue on the area of the cervix where cervical cancer most commonly starts [5]. This area is known as the squamo-columnar junction (SCJ) or T zone (transformation zone). The eversion process leaves sensitive tissue exposed to HPV transmitted during sex.
Remember, while HPV infections are common, it is only when the body is unable to clear an HPV infection for a long period of time that problems start. It could be that the reason hormonal contraception is associated with cervical cancer is that contraception–and especially prolonged use of hormonal contraception–strips the cervix of its natural defenses against HPV, eventually leading to the development of cancer.
It could be that the reason hormonal contraception is associated with cervical cancer is that contraception–and especially prolonged use of hormonal contraception–strips the cervix of its natural defenses against HPV, eventually leading to the development of cancer.
What does this mean for women using or considering hormonal birth control?
We have a really helpful article on understanding cancer risk with birth control use here. To sum it up, a 19% increased risk of developing cervical cancer is relative to the risk someone not taking birth control would have. It does not mean that a woman taking birth control has a 19% chance of getting cervical cancer. The Danish study explained this well in their conclusion. They wrote that they would expect to see one extra case of cervical cancer for every 14,706 women using oral contraception in the course of one year.
1 in 14,706 seems like pretty good odds…
Of course, one extra case of cervical cancer per 14, 706 birth control users may not seem like a lot. But consider that millions of women take hormonal contraception year after year and that cervical cancer risk increases the longer you take it. It should also be noted that other studies have found the relative risk of developing cervical cancer with contraception use to be much higher than 20%, in some cases more than double. And for anyone who has had or supported someone through a battle with cancer, even “one extra case” is one case too many.
