Cervical Malignancy

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  • Most cervical cancers begin in the transformation zone.
  • 60–75% are from squamous epithelium and 25–40% are glandular.


  • 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. However, in recent years, there has been an increase in incidence in women aged 30 to 35 years.

  • In 2018, the American Cancer Society (ACS) estimates 13,240 new cases of invasive cancer and 4,170 deaths in the United States.
  • In the United States, Hispanic women are at highest risk followed by African Americans, Asians, and whites. American Indians and Alaskan natives have the lowest risk, perhaps attributed 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 70% of all 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 in turn inactivate p53 and Rb tumor suppressor genes.
  • Tumor growth is via lymphatic and hematogenous spread (Halstedian growth).

Risk Factors

  • Persistent HPV infection is the primary risk factor for developing cervical cancer.
  • HPV infection has high prevalence with nearly 80 million people infected in the United States and 14 million new cases each year worldwide.
  • Other risk factors include:
    • Lack of or decreased access to health care and ability to obtain 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

General Prevention

  • Education on vaccination, safe sex practices, and smoking cessation are the cornerstone of prevention.
  • HPV vaccines protect against the most common HPV strains associated with cervical cancer development, 16 and 18, as well the strains responsible for warts (6 and 11).
  • There are three kind of FDA-approved vaccines, Gardasil 4, Gardasil 9, and Cervarix.
  • Vaccination is recommended for:
    • Girl and boys ages 11 or 12 years, respectively, in 2 doses with 6 to 12 months apart
    • Children ≥14 years should receive 3 doses over the course of 6 months.
    • Immunocompromised patients ages 9 through 26 years, men who have sex with men, and the LGBTQ community
    • Women ages 9 through age 26 years
    • Men ages 9 through age 21 years
  • Routine screening with Pap smear (or 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.
  • 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:
    • Cytology alone every 3 years between 21 and 29 years of age (1)[A]
    • Cytology plus HPV testing every 5 years after 30 years (1)[A]. 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, vagina, oral and oropharyngeal cancers

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