Description

Cervical cancer is a malignant neoplasm arising from the cells of the uterine cervix. Most cervical cancers, almost 90%, are squamous cell carcinomas and begin in the squamocolumnar junction where the exocervix and endocervix meet, also known as the transformation zone. A small percentage of cervical cancers are adenocarcinomas and begin in the glandular cells of the endocervix.

Epidemiology

Incidence

• According to the American Cancer Society (ACS), the annual incidence of cervical cancer in the United States between 2015 and 2019 was 7.7 cases per 100,000 person-years.
• According to the World Health Organization (WHO), cervical cancer is the fourth most common cancer in women worldwide, with 604,000 new cases and 342,000 deaths in 2020, 90% of which were in low and middle income countries.
• In the United States, cervical cancer is most frequently diagnosed in the 35 to 44 years age group, with average age at diagnosis being 50 years. Women >20 years of age rarely get cervical cancer. However, >20% of cervical cancer cases are in women >65 years of age.

Prevalence
In 2023, the ACS estimates 13,960 new cases of invasive cervical cancer and 4,310 deaths due to cervical cancer in the United States.

Etiology and Pathophysiology

• Human papillomavirus (HPV) infection with high-risk (HR) serotypes, especially HPV 16 and HPV 18, is the most important etiologic factor.
• HPV infection has high prevalence with most sexually active adults having it at one point in their lives.
• HR HPV accounts for 99% of all cervical cancer.

Genetics
There is a broad separation of HPV types, and the HR types that can be tested include HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68.

Risk Factors

• Persistent HPV infection is the primary risk factor for developing cervical cancer.
• Other risk factors include lack of or decreased access to health care and ability to obtain regular Pap tests, early coitarche especially before the age of 18 years, multiple sexual partners, unprotected sex, a history of sexually transmitted infections (STIs), low socioeconomic status, first birth prior to age of 20 years, high parity (≥3 full-term deliveries), cigarette smoking (doubles the risk), immunosuppression (HIV/AIDS, chemotherapy), diethylstilbestrol (DES) exposure in utero, oral contraceptive use of ≥5 years (risk back to baseline after ≥10 years of nonuse), family history of cervical cancer

General Prevention

• The cornerstone of prevention includes not only routine screening with a Pap test (or HPV test) but also vaccination against HR-HPV.
• The three FDA-approved vaccines are four-serotype Gardasil 4, nine-serotype Gardasil 9, and two-serotype (HPV 16 and 18) Cervarix, but only Gardasil 9 is currently distributed.
• Vaccination is recommended for:
  • Everyone through the age of 26 years
  • Girls and boys ages 11 or 12 years in 2 doses, 6 to 12 months apart. It can also be given as early as 9 years of age.
  • Children aged ≥15 years should receive 3 doses over the course of 6 months.
  • Immunocompromised patients ages 9 to 26 years, men who have sex with men, and the LGBTQ community
• Current guidelines from the US Preventive Services Task Force (USPSTF) recommend screening as follows:
  • Women aged 21 to 29 years: cytology alone every 3 years
  • Women aged 30 to 65 years: cytology alone every 3 years, HR-HPV testing (using an assay specifically approved by the FDA for HPV-screening-only testing) alone every 5 years, or cytology plus HR-HPV cotesting every 5 years
• An alternative screening algorithm using a risk-based strategy and specific FDA-approved high-risk HPV tests followed by cytology for positive screens is a recommended alternative.

Commonly Associated Conditions

Condyloma acuminata, preinvasive/invasive lesions of the vulva, vagina, oral, anal, and oropharyngeal cancers