Cervical cancer

ALSO KNOWN AS: Cervical squamous cell/adenocarcinoma, cervical intraepithelial neoplasm (CIN)

RELATED CONDITIONS: Squamous intraepithelial lesion (SIL), dysplasia, human papillomavirus (HPV) infection

DEFINITION: Cervical cancer is a slow-growing cancer in the female reproductive organs. The two primary types of cervical cancer are squamous cell carcinoma and adenocarcinoma. Classified by microscopic examination, squamous cell carcinoma accounts for 90 percent of diagnosed cases. The majority of the remaining cases are classified as adenocarcinoma, a cancer that develops from the mucus-producing gland cells in the endocervix. Additionally, a very small minority of cervical cancer cases demonstrate characteristics of both types and are therefore classified as adenosquamous or mixed carcinomas.

Risk factors: The most significant risk factor for developing cervical cancer is infection with high-risk types of human papillomavirus (HPV). HPV is sexually transmitted, and certain sexual behaviors can increase the risk of infection: sex at an early age, multiple sexual partners (directly or indirectly through a partner who has multiple sexual partners), and sex with an uncircumcised partner. Although the use of condoms does not eliminate the potential for HPV infection because any skin-to-skin contact can be sufficient to transmit the virus, condoms nonetheless do provide limited protection.

Studies have identified the following additional risk factors:

• Obesity/low-fiber diet
• Smoking
• Concomitant infection with another sexually transmitted disease such as human immunodeficiency virus (HIV), herpes simplex virus (HSV), or chlamydia
• Long-term oral contraceptive use
• Multiple full-term pregnancies
• In utero exposure to diethylstilbestrol (DES, a hormone prescribed from 1940 to 1971 for some pregnant patients considered at high risk for miscarriage)
• Family history of cervical cancer

Etiology and the disease process: Human papillomavirus (HPV) is a group of more than one hundred distinct viruses, with approximately forty strains capable of infecting the genital tract. Researchers have classified fifteen HPV types as high risk for cancer development, with a nearly two-thirds prevalence of types 16 and 18 in cervical cancer samples. In the vast majority of cases, HPV infection is spontaneously cleared by a healthy immune system. In a minority of cases, however, the virus can remain latent for years before eventually converting normal cervical cells to cancerous ones. Because only a small percentage of women infected with HPV progress to cervical cancer, lifestyle and immune system competence are believed to play a vital role in the progression of the disease.

Incidence: Globally, cancer of the cervix is the fourth most common type of cancer among women. Approximately 660,000 new cases were diagnosed in 2022, which resulted in 350,000 deaths. More than 94 percent of these mortalities occurred in low and middle-income nations. In the U.S., 13,820 new cases are projected for 2024, with 4,360 deaths predicted.

Symptoms: Early cervical cancer does not generally produce any distinguishable signs or symptoms. Abnormalities found in screening tests are the most common and effective method for detecting the presence of precancerous and cancerous cervical cells. As untreated disease progresses, symptoms may include unusual vaginal bleeding (after intercourse, between periods, postmenopausal), watery, bloody, and foul-smelling vaginal discharge, pelvic pain, or pain during intercourse.

Screening and diagnosis: Extensive cervical screening programs designed to detect early, precancerous cervical changes are well established in most developed countries. Exfoliative cytology (Pap test) is the primary component of these programs, although molecular HPV deoxyribonucleic acid (DNA) testing is also commonly incorporated. Colposcopy is a second-level diagnostic procedure used as a follow-up to abnormal screening results.

Named after the physician who developed the procedure (Papanikolaou), exfoliative cytology, or Pap test, is a screening procedure involving the collection and microscopic evaluation of cervical cells. During a routine pelvic examination, cervical cells are collected by broom, brush, spatula, or other means. These cells are either smeared directly onto a microscope slide (as in the traditional, “dry” Pap smear) or transferred into a liquid medium to concentrate the cells for subsequent transfer onto a slide. This new liquid-based cytology has demonstrated greater test sensitivity because more cells can be analyzed.

The HPV DNA test is a molecular analysis of a cervical sample to determine the presence of HPV and its type. This test is used in conjunction with an abnormal Pap test as an additional diagnostic tool.

A colposcopy is a pelvic examination in which a light source and binocular microscope are used to enable a direct magnified inspection of the patient’s cervix, vagina, and vulva. Application of a weak acetic acid solution also serves to highlight any suspicious abnormalities.

Following abnormal screening results, additional tests may be ordered to confirm diagnosis and determine how far the cancer has spread (staging):

• Biopsy: Allows for analysis of a small section of tissue collected from the cervix.
• Proctoscopy: Allows for a visual inspection of the rectum for the presence of cancer.
• Imaging: imaging such as X ray, magnetic resonance imaging, computed tomography, and positron emission tomography provides patient/organ appropriate imaging to inspect for cancer spread (metastasis).

Cervical cancer is staged based on tumor size, invasive nature, and degree of metastasis (spread to lymph nodes/organs). Cervical cancer is staged with the International Federation of Gynecology and Obstetrics (FIGO) system:

Treatment and therapy: Treatment of cervical cancer largely depends on the disease stage. The three treatment options are surgery, radiation, and chemotherapy.

Surgical removal is used primarily for nonmetastatic lesions. Cryosurgery uses a metal probe cooled with liquid nitrogen to freeze cancerous cells. Laser surgery uses a laser to burn (vaporize) cancerous cells. In conization, a thin, heated wire (LEEP, or loop electrosurgical excision procedure) or surgical/laser knife (cold knife cone biopsy) removes the affected tissue. Rarely used as a sole treatment, conization aids in diagnosis before additional surgery or alternative treatment. In a hysterectomy, the degree of the removal of uterine tissuesimple vs. radicaldepends on the stage and patient circumstances.

Radiation employs high-energy X-rays to kill cancer cells, either externally through external beam radiation or internally via a radioactive capsule called brachytherapy.

Chemotherapy uses anticancer drugslike cisplatin, paclitaxel, topotecan, ifosfamide, or fluorouraciltaken orally or intravenously to treat metastasized cancer.

In September 2021, the U.S. Food and Drug Administration approved an antibody-drug treatment called Tivdak (tisotumab vedotin) to help counteract recurrent or metastatic cervical cancer. This was a targeted treatment that worked to deliver chemotherapy to infected cancer cells. Early results were positive. A reported 24 percent of the patients in the clinical trial experienced complete remission, while 49 percent were able to stabilize the disease.

Immunotherapies are now employed in the fight against cervical cancer. These work by triggering proteins in immune cells to turn themselves on or off, depending on the required action. This creates an immune response to the presence of cancer cells.

Prognosis, prevention, and outcomes: Early detection through effective screening programs offers a high probability for complete cancer eradication. Continued adherence to annual cervical screening and healthy habits is integral to continued remission.

A new vaccine, Gardasil, approved by the Food and Drug Administration offers protection against the most dangerous, high-risk HPV types 16 and 18. It also protects against types 6 and 11, which cause genital warts. For greatest efficacy, the vaccine should be administered before the patient has become sexually active. The Federal Advisory Committee on Immunization Practices (ACIP) recommends vaccination for girls aged eleven and twelve. The committee also recommends that nonvaccinated women from age thirteen to twenty-six receive catch-up vaccinations. Although the American Cancer Society (ASC) agrees with the initial vaccination protocol, it recommends catch-up vaccinations for young women aged thirteen to eighteen only. ACS recommends that older women discuss the potential benefit of the vaccination with regard to their personal risk factors for previous exposure to HPV.

Bibliography

Devita, Vincent T., Jr., Samuel Hellman, and Steven A. Rosenberg, eds. Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Lippincott Williams & Wilkins, 2005.

"Cervical Cancer." World Health Organization, 5 Mar. 2024, www.who.int/news-room/fact-sheets/detail/cervical-cancer. Accessed 1 July 2024.

Highleyman, Liz. "Newly Approved Treatment Shows Promise for Advanced Cervical Cancer." Cancer Health, 24 Sept. 2021, www.cancerhealth.com/article/newly-approved-treatment-shows-promise-advanced-cervical-cancer. Accessed 1 July 2024.

"Immunotherapy for Cervical Cancer." American Cancer Society, 20 Mar. 2024, www.cancer.org/cancer/types/cervical-cancer/treating/immunotherapy.html. Accessed 1 July 2024.

"Key Statistics for Cervical Cancer." American Cancer Society, 17 Jan. 2024, www.cancer.org/cancer/types/cervical-cancer/about/key-statistics.html. Accessed 1 July 2024.

Saslow, D., et al. “American Cancer Society Guideline for Human Papillomavirus (HPV) Vaccine Use to Prevent Cervical Cancer and Its Precursors.” CA: A Cancer Journal for Clinicians, vol. 57, 2007, pp. 7-28.

Stewart, Bernard W., and Paul Kleihues, eds. World Cancer Report. Lyon, France, IARC Press, 2003.

"What is Cervical Cancer?" National Cancer Institute, 15 June, 2023, www.cancer.gov/types/cervical. Accessed 1 July 2024.