HPV and cervical cancer: understanding the link

Cervical cancer is one of the top 10 leading causes of cancer deaths in women, according to the Centers for Disease Control and Prevention (CDC) (CDC, 2019). Fortunately, it is also one of the most preventable. Despite this, over 13,000 women are diagnosed with invasive cervical cancer yearly in the United States (ACS, 2019).

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The cervix is the lower part of the uterus (womb) and connects the uterus to the vagina. Cancer of this area (cervical cancer) occurs when abnormal cells grow unchecked. To better understand cervical cancer, you need to understand the anatomy of the cervix.

Your cervix has two parts: endocervix and ectocervix. The endocervix is the part of the cervix that is closest to the uterus; it has the “glandular” cells that produce mucus. The portion that is closest to the vagina is called the ectocervix (or exocervix) and is covered in “squamous” cells (thin flat cells). These two parts of the cervix meet at the “transformation” zone (where one type of cell lining “transforms” to another).

Why does this matter? Different cell types give rise to different kinds of cervical cancer. Cervical cancer happens when healthy cervical cells no longer grow normally; they are “out of control” and form a mass of tissue (tumor) that can then invade other tissues. Initially, this will look like abnormal cervical cells (cervical dysplasia or precancers) and can only be detected with screening. If left untreated, these precancerous lesions can turn into cervical cancer. Most cervical cancers arise in the transformation zone (where the two types of cells meet) and then transform into either squamous cell carcinoma (cancer) or adenocarcinoma; rarely, cervical cancer can involve both kinds of cells.

• Squamous cell cancer — starts in the cells of the ectocervix; this type accounts for 80-90% of cervical cancers (ACS, 2019)

• Adenocarcinoma — originates in the endocervix and makes up the other 10-20% of cervical cancers

Cervical cancer tends to affect women in their mid-30s and 40s. However, more than 15% of cases are in women over the age of 65; this highlights the importance of continued surveillance, even after menopause (ACS, 2019). Women younger than 20 generally do not develop cervical cancer. In the U.S, Hispanic women have the highest incidence of cervical cancer, followed by African-Americans, Asians, and whites (ACS, 2019).

Cervical cancer typically does not have any symptoms in the early stages. Once more advanced cancer develops, women may experience symptoms such as:

• Bleeding between periods or after menopause

• Heavy or abnormal discharge that may be thick or watery; may have a foul odor

• Bleeding or pain after intercourse

• Pelvic pain not connected to your periods

• Pain during urination (dysuria) or needing to go more often (increased frequency)

Infection with human papillomavirus (HPV) is implicated in over 95% of cervical cancers (Small, 2017). HPV spreads by skin-to-skin contact and is such a common sexually transmitted infection (STI) that more than 80% of sexually active adults will get infected at some point in their lives (NFID, 2019). There are over 100 strains of HPV, but only a few that lead to cervical cancer, also known as “high-risk HPV.” Types 16 and 18 are present in 66% of cervical cancers; another 15% are linked to HPV types 31, 33, 45, 52, and 58 (MMWR, 2015).

Most people who get HPV never have any symptoms and clear it from their system within a year or two, even the high-risk types. However, 10% of women with high-risk HPV types have a persistent infection in the cells of the cervix, increasing their risk of developing cervical cancer (CDC, 2018). The mechanism is not well understood, but persistent high-risk HPV infection causes healthy cells to grow abnormally and form precancers or cervical dysplasia. If left untreated, these precancers can turn into cervical cancer.

HPV infection is a large part of the development of cervical cancer. However, most women with HPV do not get cervical cancer. So why do some women seem more susceptible to it? Factors that change the DNA in your cells (such as smoking) or decrease the ability of your immune system to fight off an HPV infection (like HIV) will increase your chances of developing cervical cancer when exposed to the high-risk HPV types.

• HPV: This is the most important risk factor for cervical cancer. HPV infection is implicated in almost all cases of cervical cancer. If you haven’t already, discuss the option of getting the HPV vaccine with your healthcare provider. 

• Compromised immune system: The immune system plays a vital role in clearing infection as well as killing off cancer cells. Anything that decreases the body’s ability to perform these functions will increase the risk of cervical cancer. This includes human immunodeficiency virus (HIV) and the use of medications to suppress the immune system, like steroids, for example. 

• Smoking: When you smoke, you expose the cells in your body to chemicals that can affect cell DNA, making healthy cells act abnormally; this is why smoking is a risk factor for so many cancers. Women who smoke are twice as likely as non-smokers to get cervical cancer. Researchers looking at the cervical mucus of women who smoke have found tobacco derivatives that they believe may change the DNA of the cervical cells. Smoking also decreases the ability of the immune system to clear HPV infections, leading to persistent HPV in the body.

• Age: Cervical cancer develops most often in women in their 30s and 40s; however, up to 15% of cases are in women over 65. This usually occurs in women who have not been getting regular Pap testing. Cervical cancer is rarely seen in women less than 20 years old. Screening with Pap tests generally starts at age 21 and continues through age 65. An HPV infection can turn into cancer months or years after the initial infection. 

• Oral contraceptive pills (OCPs): According to the American Cancer Society, using OCPs increases the risk of cervical cancer (ACS, 2019). The risk increases the longer you take OCPs but decreases again after you stop. The risk normalizes approximately ten years after discontinuing OCPs. Talk to your healthcare provider about whether OCPs are right for you. 

• Socioeconomic factors: Women from lower socioeconomic backgrounds have a higher risk of getting cervical cancer. This is most likely because of their lack of access to healthcare, including cervical cancer screening. 

• Exposure to diethylstilbestrol (DES): DES was used between 1940 and 1971 to prevent miscarriage in women. If your mother took DES while she was pregnant with you, you have an increased risk of developing a specific type of cervical cancer: clear-cell adenocarcinoma. Let your healthcare provider know if this applies to you. 

The first HPV vaccine was introduced in 2006, and currently, there are three FDA-approved HPV vaccines. All three cover HPV types 16 and 18 (the two types most likely to cause cervical cancer), but most recently a 9-valent vaccine (Gardasil 9, by Merck & Co, Inc) that is effective against nine different types of HPV was released: types 6, 11, 16, 18, 31, 33, 45, 52, and 58. This vaccine covers the five additional strains that have been associated with 15% of cervical cancers. All three of these vaccines are both safe and effective and are approved for use in both boys and girls.The CDC HPV vaccine recommendations are as follows (CDC, 2016):

• Vaccination can start as early as age 9, but routine HPV vaccination for girls and boys usually starts at age 11 or 12.

• Teens and young women can get the HPV vaccine up to 27 years of age, and healthy young men can get vaccinated until they are 22 years old.

• Men who have sex with men or people with weak immune systems (like those with HIV) can get the vaccine before age 26.

• Transgender individuals can get the HPV vaccine up to 27 years of age.

• Unvaccinated adults 27-45 years of age should talk to their provider and use shared clinical decision-making regarding HPV vaccination.

Since the increased use of the HPV vaccine, infections with HPV types that cause genital warts and most of the HPV cancers, including cervical cancer, have dropped 86% in teenage girls and 71% in young women (CDC, 2019). Also, the percentage of precancerous cervical lesions has fallen by 40% in vaccinated women. Early adoption of the HPV vaccine can prevent infection with high-risk HPV, thereby significantly decreasing your risk of getting cervical cancer in the future.

Cervical cancer does not cause symptoms until it is in advanced stages; however, it is very treatable if it is detected early. Screening tests are crucial for a woman’s heath, especially given the high prevalence of HPV. Cervical cancer is both treatable and preventable if you take the appropriate steps.Your provider may perform a Pap test (aka Pap smear) to examine the structure (cytology) of the cervical cells to look for any abnormalities that might suggest precancerous changes (cervical dysplasia). You will be asked to lie on the exam table with your feet in supports (stirrups). Your provider will use a speculum to open the vagina, examine the cervix, and collect cervical cell samples. The Pap test does not test for HPV; however, if abnormalities are seen in the cells (positive Pap test), then DNA testing for HPV is done. The U.S. Preventive Services Task Force (USPSTF) cervical cancer has specific screening guidelines for healthy women who have not previously been diagnosed with cervical cancer or a high-grade lesion, who are not immunocompromised (such as those with HIV), and who did not have exposure to DES (Moyer, 2012):

• Women should begin screening with the Pap test at age 21

• Women have three options available for screening at age 30 and above: pap test every three years, co-testing with Pap and HPV DNA test every five years, or HPV DNA test alone every five years

• Women under age 21 should not get routine Pap tests.

• Women over age 65 should not get routine routinely tested if they had been getting appropriate prior screenings, and their Pap test has been normal (negative Pap results). Talk to your doctor if you have had abnormal cells noted on your Pap tests or were not being screened regularly, as you may need additional testing.

There is another method of testing used in other countries but is not yet available routinely in the U.S. — self-sampling. In this method, you take a vaginal swab and send the cell samples by mail for HPV testing. According to the data from other countries, self-sampling appears to be as accurate as provider-collected sampling (Gupta, 2018). It is not approved for routine use in the U.S., but it may become available in the future, leading to increased access to HPV testing and cervical cancer screening.You should talk to your healthcare provider about which option for cervical testing is right for you.

If your Pap test comes back positive, this does not mean that you have cervical cancer; it only means that some abnormal cells were found. Your healthcare provider will test the abnormal cells for the presence of high-risk HPV (if an HPV test was not already done). This may be followed up by colposcopy and a biopsy. In a colposcopy, a speculum is used to visualize the cervix, just like in the pap test. But this time, your provider will use a scope with a bright light to get a more detailed look at any potentially abnormal areas. Sometimes a vinegar solution is placed on the cervical tissue; it turns white in the presence of abnormal cells. If needed, a biopsy may be done using either of the following methods (or both in most cases):

• Punch biopsy — a small piece of cervical tissue is pinched off and sent for testing

• Endocervical curettage — tissues cells are scraped off the cervix

Depending on the results of the biopsy, your provider may need to obtain more tissue from deeper layers in the cervix using

• Loop electrosurgical excision procedure (LEEP) - a wire loop is heated by an electrical current and removes abnormal cells from the cervix

• Cold Knife Cone biopsy- uses a scalpel or laser to remove a cone-shaped piece of deeper cervical tissue containing abnormal cells

Early-stage cervical cancer is usually treated by the removal of the cancer cells via surgery; the extent of surgery will depend on the size of the cancer. There are several options for surgery:

• Just the part of the cervix with cancer is removed

• The entire cervix is removed (trachelectomy)

• The entire cervix and uterus are removed, along with part of the vagina and nearby lymph nodes (radical hysterectomy)

There are non-surgical treatments as well. Radiation, chemotherapy, and immunotherapy (medications that boost your immune system) are all treatment options, and sometimes a combination of therapies is needed.

Cervical cancer is one of the leading causes of cancer deaths among women and worldwide; it is the fourth most common cancer in women (Small, 2017). Fortunately, the advent of the HPV vaccine has led to a decrease in the infection rates with the high-risk strains of HPV as well as the rates of precancerous lesions. Women need to remain vigilant; there are no early warning signs, so screening is crucial. Talk to your healthcare provider to make sure that you are being screened appropriately and get the HPV vaccine if appropriate.

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Every article on Health Guide goes through rigorous fact-checking by our team of medical reviewers. Our reviewers are trained medical professionals who ensure each article contains the most up-to-date information, and that medical details have been correctly interpreted by the writer.

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Current version

September 17, 2019

Written by

Chimene Richa, MD

Fact checked by

Tzvi Doron, DO

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About the medical reviewer

Tzvi Doron, DO

Dr. Tzvi Doron is Board Certified in Family Medicine by the American Board of Family Medicine.