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- Invasive cancer of the uterine cervix
- Most cervical cancers begin in the transformation zone. 60–75% of the cancers originate from squamous epithelium.
- 25–40% of the cancers are adenocarcinomas. These are more difficult to diagnose by cytology.
- Commonly involves the vagina, parametria, and pelvic side walls
- Invasion of bladder, rectum, and other pelvic structures can be seen in advanced stages.
- Cervical cancer is the second most common malignancy in women worldwide and the most common gynecologic cancer.
- The disease has a bimodal distribution, with the highest risk among women aged 40 to 59 years and >70 years.
- In recent years, there has been an increase in incidence in women aged 30 to 35 years.
- In 2017, the American Cancer Society (ACS) estimates 12,820 new cases of invasive cancer in the United States and 4,210 deaths.
- The death rate has decreased by 50% in the last 40 years due to increased screening using Pap testing, which allows for early detection of atypical changes in the cells and/or invasive cancer in its most curable stage.
- In the United States, Hispanic women are at highest risk of developing cervical cancer followed by African Americans, Asians, and whites. American Indians and Alaskan natives have the lowest. This may be due to low screening rates.
Etiology and Pathophysiology
- Human papillomavirus (HPV) infection is the most important etiologic factor. Infection with serotypes 16 and 18 account for about 70% of cervical cancer.
- Persistent HPV infection promotes coding errors in the cell cycle resulting in dysplastic changes to the endocervical cellular lining.
- In addition HPV activates E6 and E7 oncogenic proteins, which inactivate p53 and Rb tumor suppressor genes. Tumor growth is via lymphatic and hematogenous spread (Halstedian growth).
- Inheritance has not been established yet, except in very rare cases of Peutz-Jeghers syndrome.
- Persistent HPV infection is the number one risk factor for developing cervical cancer. HPV infection is very common: At least 3 out of 4 persons become infected during their lifetime.
- Other risk factors include the following:
- Lack of regular Pap smears
- Early coitarche
- Multiple sexual partners
- Unprotected sex
- A history of sexually transmitted diseases (STDs)
- Low socioeconomic status
- Obesity (increases the risk for adenocarcinoma type)
- High parity (>3 full term deliveries)
- Cigarette smoking (doubles the risk)
- Immunosuppression (HIV/AIDs, chemotherapy)
- Diethylstilbestrol (DES) exposure in utero
- Education on safe sex practices and smoking cessation
- HPV vaccines: There are currently two effective vaccines in clinical use for the prevention of HPV infections.
- The vaccines provide good protection against HPV types 16 and 18 and the cervical changes caused by them in young women with no previous HPV infection. The protective benefit from the vaccines appears to last for at least 6 years.
- Gardasil vaccine: 9-valent; FDA-approved in females and in males (for prevention of genital warts and anal cancer)
- Cervarix vaccine: bivalent vaccine against oncogenic HPV strains 16 and 18
- Recommended age of vaccination is 11 to 12 years (prior to coitarche), but Gardasil is approved from 9 to 26 years and Cervarix from 10 to 25 years.
- Regular Pap smear (or likely high-risk HPV testing) is virtually the only way to identify premalignant lesions and possibly prevent progression to cancer. Screening has the potential to prevent up to 80% of cervical cancer worldwide.
- Although guideline changes are likely in 2018 to 2019, according to current guidelines from the American College of Obstetricians and Gynecologists (ACOG) and the American Society for Colposcopy and Cervical Pathology (ASCCP) screening should be performed as follows:
- The International Federation of Gynecology and Obstetrics (FIGO) recommends visual inspection with acetic acid (VIA) or Lugol iodine (VILI) as alternatives to Pap smears in resource-poor settings (2)[C].
- Despite HPV vaccination, cervical cancer screening will remain the main preventive measure for both vaccinated and unvaccinated women.
Commonly Associated Conditions
- Condyloma acuminata
- Preinvasive/invasive lesions of the vulva and vagina