Cervical cancer is a type of cancer that develops in the cervix, the lower narrow part of the uterus (womb). It is due to the abnormal growth of cells that can invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal vaginal bleeding, pelvic pain or pain during sexual intercourse. While bleeding after sex may not be serious, it may also indicate the presence of cervical cancer.
Almost all cases (99%) are linked to genital human papillomavirus infection (HPV); most who have had HPV infections, however, do not develop cervical cancer. The risk is higher in people who smoke, have a weakened immune system, use birth control, start sex at a young age and have many sexual partners. Cervical cancer typically develops from precancerous changes over 10 to 20 years. About 75% of cervical cancers are squamous cell carcinomas, 20–25% are adenocarcinoma. Diagnosis is typically by cervical screening followed by a biopsy. Medical imaging is then done to determine whether or not the cancer has spread beyond the cervix.
HPV vaccination is the most cost-effective public health measure against cervical cancer. HPV vaccines protect against two to seven high-risk strains of this family of viruses and may prevent up to 90% of cervical cancers. By the end of 2024, 147 countries provided the HPV vaccine in their national immunization schedule for girls. As of 2022, 47 countries also did it for boys. As they do not prevent all cervical cancer, guidelines recommend regular screening. Cervical screening allows for the detection of pre-cancer, which can be treated to prevent the development of cancer. Treatment may consist of some combination of surgery, chemotherapy, radiation therapy, and immunotherapy. Five-year survival rates in the United States are 69%, but outcomes depend on how early the cancer is detected.
Worldwide, cervical cancer is both the fourth-most common type of cancer and the fourth-most common cause of death from cancer in women, with over 660,000 new cases and around 350,000 deaths in 2022. This is about 8% of the total cases and total deaths from cancer. Almost 90% of cases and deaths occur in low- and middle-income; it makes up 17% of overall cancer cases in women in these countries, compared to 2% in high-income countries. In developed countries, the widespread use of cervical screening programs has dramatically reduced rates of cervical cancer. In medical research, the most famous immortalized cell line, known as HeLa, was developed from cervical cancer cells of a woman named Henrietta Lacks.
The Cervical Cancer Elimination Day of Action is 17 November. The date marks the day in 2020 when the WHO launched the global strategy to accelerate the elimination of cervical cancer as a public health problem, with a resolution passed by 194 countries.
Signs and symptoms The early stages of cervical cancer may be completely free of symptoms. Vaginal bleeding, contact bleeding (one most common forms being bleeding after sexual intercourse), or (rarely) a vaginal mass may indicate the presence of cervical cancer. Also, moderate pain during sexual intercourse and vaginal discharge are symptoms of cervical cancer. Bleeding after douching, in between periods or after menopause are also common signs. In advanced disease, metastases may be present in the abdomen, lungs, or elsewhere.
Symptoms of advanced cervical cancer may include loss of appetite, weight loss, fatigue, pelvic pain, back pain, leg pain, swollen legs, heavy vaginal bleeding, bone fractures, and (rarely) leakage of urine or faeces from the vagina. Other signs of locally advanced disease (as the cancer invades organs in the pelvis) include an enlarged kidney with flank pain as urine flow from the kidneys to bladder is blocked, leg swelling and blood clots in the legs as pelvic veins are blocked, rectal bleeding, and bleeding in the urine.
Causes
Infection with some types of HPV is the greatest risk factor for cervical cancer, followed by smoking. HIV infection is also a risk factor.
Human papillomavirus Infection with HPV is thought to be required for cervical cancer to occur. HPV types 16 and 18 are the cause of 75% of cervical cancer cases globally, while 31 and 45 are the causes of another 10%.
Women who have multiple sexual partners, or have partners who have multiple sexual partners, regardless of sex, are at higher risk of cervical cancer.
Over 200 types of HPV known, 12 are classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59), three as probable high-risk (26, 53, and 66), and 12 as low-risk (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108). Most cases of squamous cell carcinomas of the cervix are due to HPV type 16 and most cases of adenocarcinoma are due to HPV type 18. High risk HPV viral subtypes can integrate their DNA into the host genome and induce transcription of the viral cancer causing proteins E6 and E7. E6 degrades the tumor suppressing protein p53 and E7 degrades and inactivates the tumor suppressing protein pRb. The loss of p53 and pRb leads to increased blood vessel growth feeding tumors (via vascular endothelial growth factor (VEGF) over-expression), loss of tumor cell suppression and cell cycle regulation disruptions, all of which can lead to cervical cancer.
Genital warts, which are a form of benign tumor of epithelial cells, are also caused by various strains of HPV. However, these serotypes are usually not related to cervical cancer. Having multiple strains at the same time is common, including those that can cause cervical cancer along with those that cause warts.r
Co-infections and immunosuppression Having a HPV infection at the same time with other sexually transmitted infections increases risks. This includes HIV and trich (a parasitic infection) and likely chlamydia. A HIV infection makes it more difficult for the body to clear the HPV infection. Women with inflammatory bowel disease who are on immunosuppressive medication also have a higher chance of developing cervical cancer.
Smoking
Cigarette smoking, both active and passive, increases the risk of cervical cancer. Among HPV-infected women, current and former smokers have roughly two to three times the incidence of invasive cancer. Passive smoking is also associated with increased risk, but to a lesser extent. Smoking negatively affects the immune system, making it more difficult for the body to fight off a HPV infection: the virus persists for longer. Smoking can also increase the risk a HPV infection leads to cancer.
Oral contraceptives Long-term use of oral contraceptives is associated with increased risk of cervical cancer in women who have had HPV. Women who have used oral contraceptives for 5 to 9 years have about three times the incidence of invasive cancer, and those who used them for 10 years or longer have about four times the risk.
Multiple pregnancies Having many pregnancies is associated with an increased risk of cervical cancer. Among HPV-infected women, those who have had seven or more full-term pregnancies have around four times the risk of cancer compared with women with no pregnancies, and two to three times the risk of women who have had one or two full-term pregnancies.
Prevention
Vaccination
Six HPV vaccines are licensed: three bivalent vaccines that protect against two HPV types, two quadrivalent vaccines covering four types, and one nonavalent vaccine that protects against nine types. Three HPV vaccines (Gardasil, Gardasil 9, and Cervarix) reduce the risk of cancerous or precancerous changes of the cervix and perineum by about 93% and 62%, respectively. All have excellent safety profiles and are highly efficacious, or have met immunobridging standards. The vaccines are between 92% and 100% effective against HPV 16 and 18.
The main target group for HPV vaccination is young adolescent girls, aged 9–14, who get one dose. For older girls and women, and for those living with HIV or otherwise immonocompromised, additional vaccines may be necessary. As of 2022, 125 countries include HPV vaccines in their routine vaccinations for girls, and 47 countries recommend them for boys, as well.
Many girls in low- and middle-income countries do not have access to the vaccine. Initially, two doses of the vaccine were given for everyone, but the WHO recommendation changed as it has appeared that a single dose is normally as effective as multiple doses. The WHO goal is to get 90% of girls vaccinated by 2030, up from 13% in 2021. This is more achievable on the new single-dose schedule.
Screening
Cervical screening for pre-cancerous changes is highly effective in preventing cervical cancer cases and deaths. Different screening methods are in use. The WHO recommends testing for HPV infections as the primary method of screening, but , most countries still used a Pap test, which examines cells for (pre)cancerous changes directly. Visual inspection with acetic acid was used in many low-resource regions; the WHO recommends a rapid change to HPV testing for these regions, as accuracy is quite low.
Screening can reveal who is at risk of, or who has abnormal cells on the surface of the cervix called cervical intraepithelial neoplasia (CIN). These precancerous changes can be confirmed with an internal examination known as colposcopy. Low-grade CIN often goes away by itself, but higher-grade CIN frequency changes into cancer later.
The World Health Organization (WHO) recommends screening starts at 30 years of age, except for those living with HIV, where it recommends screening to start at age 25. The 2025 European guidelines recommend screening women between 25 and 64 years using a HPV test. For those between 65 and 69, testing is recommended if there has not been a screening in the last 10 years. In the United States, testing starts at 21.
Recommended intervals depends on the country, type of test, and population risk levels.The WHO recommends a screening interval of 5–10 years for a HPV test, which is increased to 3–5 years for those living with HIV. For countries still using Pap tests, this would be every 3 years. In the United States, screening is recommended to take place every 3 years for a Pap test and every 5 years for a HPV test. HPV vaccination status does not change screening rates.
People who test positively on a HPV test or a Pap smear test, but then negatively during a closer inspection in a colposcopy are recommended to be retested more frequently. The same is true for those who were treated for (pre-)cancer, often after 12 months.
Screening promoting strategies Personal invitations encouraging women to get screened are effective at increasing the likelihood that they will do so. Educational materials also help increase the likelihood that women will go for screening, but they are not as effective as invitations.
Interventions can help increase rates of cervical cancer screenings, specifically among low and middle-income countries. In efforts to increase life-saving screenings, interventions have proved successful. Single interventions include reminding patients via phone calls, SMS, and subsidized or free services. Combined interventions include multiple steps and can be more effective than single interventions, specifically health education combined with SMS. These interventions make cervical cancer screenings more accessible and less daunting for many at-risk women.
Condoms
The use of condoms during sexual intercourse decreases but does not eliminate the risk of transmitting the infection. Condoms help protect against infection when used for vaginal, anal and oral sex. They do not necessarily cover all the areas infected with HPV, so they do not offer full protection.
Nutrition Vitamin A is associated with a lower risk as are vitamin B12, vitamin C, vitamin E, and beta-Carotene.
Diagnosis
Biopsy