Cervical Malignancy

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Basics

Description

  • Cervical cancer is a malignant neoplasm arising from the uterine cervix.
  • Most cervical cancers begin in the transformation zone.
  • 60–75% are from squamous epithelium and 25–40% are glandular.

Epidemiology

Incidence
  • 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.

Prevalence
  • 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 with high-risk (HR) serotypes is the most important etiologic factor.
  • HPV infection has high prevalence with nearly 80 million people infected in the United States and 14 million new cases each year worldwide.
  • HR serotypes 16 and 18 account for 70% of all cervical cancer.
  • Persistent HR-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.
  • Other risk factors include lack of or decreased access to health care and ability to obtain regular Pap tests, early coitarche, multiple sexual partners, unprotected sex, a history of sexually transmitted infections (STIs), low socioeconomic status, obesity (increases the risk for adenocarcinoma type), Nonwhite race, 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 not only includes routine screening with a Pap test (or HPV test) but also vaccination against HR-HPV. Also, important is education on safe sex practices and smoking cessation.
  • HPV vaccines protect against HPV serotypes most commonly associated with cervical cancer development, 16 and 18, as well the serotypes responsible for warts (6 and 11).
  • The three FDA-approved vaccines are four-serotype Gardasil 4, nine-serotype Gardasil 9, and two-serotype (HPV 16 and 18) Cervarix.
  • 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 ≥15 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
  • Routine screening with a Pap test (or HPV test) is essential for identifying precursors and early-stage disease. Screening has the potential to prevent up to 80% of cervical cancer worldwide.
  • Current guidelines from the U.S. Preventive Services Task Force (USPSTF), as endorsed by the Society of Gynecologic Oncology (SGO), American College of Obstetricians and Gynecologists (ACOG), and the American Society for Colposcopy and Cervical Pathology (ASCCP), recommend screening as follows:
    • Women aged 21 to 29 years: cytology alone every 3 years (1)[C]
    • Women aged 30 to 65 years: cytology alone every 3 years or HR-HPV testing (using an assay specifically approved by the FDA for HPV-screening-only testing) alone every 5 years (2) or cytology plus HR-HPV every 5 years (1)[C]
  • An alternative screening algorithm using a risk-based strategy and specific FDA-approved HR-HPV tests followed by cytology for positive screens is a recommended alternative (2).
  • 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 (3)[C].
  • Despite HPV vaccination, cervical cancer screening remains the main preventive measure for both vaccinated and unvaccinated women.

Commonly Associated Conditions

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

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Basics

Description

  • Cervical cancer is a malignant neoplasm arising from the uterine cervix.
  • Most cervical cancers begin in the transformation zone.
  • 60–75% are from squamous epithelium and 25–40% are glandular.

Epidemiology

Incidence
  • 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.

Prevalence
  • 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 with high-risk (HR) serotypes is the most important etiologic factor.
  • HPV infection has high prevalence with nearly 80 million people infected in the United States and 14 million new cases each year worldwide.
  • HR serotypes 16 and 18 account for 70% of all cervical cancer.
  • Persistent HR-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.
  • Other risk factors include lack of or decreased access to health care and ability to obtain regular Pap tests, early coitarche, multiple sexual partners, unprotected sex, a history of sexually transmitted infections (STIs), low socioeconomic status, obesity (increases the risk for adenocarcinoma type), Nonwhite race, 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 not only includes routine screening with a Pap test (or HPV test) but also vaccination against HR-HPV. Also, important is education on safe sex practices and smoking cessation.
  • HPV vaccines protect against HPV serotypes most commonly associated with cervical cancer development, 16 and 18, as well the serotypes responsible for warts (6 and 11).
  • The three FDA-approved vaccines are four-serotype Gardasil 4, nine-serotype Gardasil 9, and two-serotype (HPV 16 and 18) Cervarix.
  • 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 ≥15 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
  • Routine screening with a Pap test (or HPV test) is essential for identifying precursors and early-stage disease. Screening has the potential to prevent up to 80% of cervical cancer worldwide.
  • Current guidelines from the U.S. Preventive Services Task Force (USPSTF), as endorsed by the Society of Gynecologic Oncology (SGO), American College of Obstetricians and Gynecologists (ACOG), and the American Society for Colposcopy and Cervical Pathology (ASCCP), recommend screening as follows:
    • Women aged 21 to 29 years: cytology alone every 3 years (1)[C]
    • Women aged 30 to 65 years: cytology alone every 3 years or HR-HPV testing (using an assay specifically approved by the FDA for HPV-screening-only testing) alone every 5 years (2) or cytology plus HR-HPV every 5 years (1)[C]
  • An alternative screening algorithm using a risk-based strategy and specific FDA-approved HR-HPV tests followed by cytology for positive screens is a recommended alternative (2).
  • 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 (3)[C].
  • Despite HPV vaccination, cervical cancer screening remains the main preventive measure for both vaccinated and unvaccinated women.

Commonly Associated Conditions

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

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