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Minimize Risk Factor Exposure

  • Human Papillomavirus (HPV) Infectiona

    • Abstinence from sexual activity; condom and/or spermicide use (RR, 0.4).

    • HPV vaccination per CDC schedule.

  • Cigarette Smoke (Active or Passive)

    • Increased risk of high-grade cervical intraepithelial neoplasia (CIN) or invasive cancer 2- to 3-fold among HPV-infected women.

  • High Parity

    • HPV-infected women with 7 or more full-term pregnancies have a 4-fold increased risk of squamous cell CA of the cervix compared with nulliparous women.

  • Long-Term Use of Oral Contraceptives (>5 y)

    • Increases risk by 3-fold.

    • Longer use related to even higher risk.

Therapeutic Approaches

  • HPV-16/HPV-18 Vaccinationb

    • Reduces incidence and persistent infections with efficacy of 91.6% (95% CI, 64.5–98.0) and 100% (95% CI, 45–100), respectively; duration of efficacy is not yet known; impact on long-term cervical CA rates also unknown but likely to be significant. Two doses of vaccine if 9- to 14-y-old, 3 doses if 15- to 26-y-old. Shared decision making for those age 27–45. (Lancet. 2009;374:1975) (N Engl J Med. 2015;372:711, 775) (ACIP 2020)

    • Also will likely decrease risk of other HPV-driven malignancies (oropharynx and anal CA).

  • Screening with PAP Smears

    • Estimates from population studies suggest that screening may decrease CA incidence and mortality by <80%. Primary HPV screening every 5 y from age 25 to 65 is preferred (ACS 2020). Cotesting with HPV testing and cytology every 5 y or cytology alone every 3 y is acceptable from age 25 to 65.

aMethods to minimize risk of HPV infection include abstinence from sexual activity and the use of barrier contraceptives and/or spermicidal gel during sexual intercourse.

bOn June 8, 2006, the US Food and Drug Administration (FDA) announced approval of Gardasil, the first vaccine developed to prevent cervical CA, precancerous genital lesions, and genital warts caused by HPV types 6, 11, 16, and 18. The vaccine is approved for use in females age 9–26 y ( A bivalent vaccine, Cervarix, is also FDA approved with activity against HPV subtypes 16 and 18 (N Engl J Med. 2006;354:1109-1112).


Minimize Risk Factor Exposure

  • Unopposed estrogen is a significant risk factor for the development of uterine cancer

    • Unopposed estrogen use in postmenopausal women for 5 or more years more than doubled the risk of endometrial CA compared to women who did not use estrogen. Other significant events include stroke (39% relative increase) and pulmonary embolus (34% relative increase). (Lancet. 2005;365:1543) (JAMA. 2004;291:1701)

    • Obesity—risk increases 1.59-fold for each 5 kg/m2 change in body mass.

    • Lack of exercise—regular exercise (2 h/wk) with 38%–48% decrease in risk.

    • Tamoxifen—used for >2 y has a 2.3- to 7.5-fold increased risk of endometrial CA (usually stage I—95% cure rate ...

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