Cancer Health Center

Background

Natural history, incidence, and mortality

In the United States in 2011, it is estimated that 12,710 cases of invasive cervical cancer will be diagnosed and that 4,290 women will die of the disease.[1] These rates have been improving steadily. Mortality rates declined from 1975 to 2003, but have remained stable since 2003.[1] This improvement has been attributed largely to screening with the Papanicolaou (Pap) test.

Invasive squamous carcinoma of the cervix results from the progression of preinvasive precursor lesions called cervical intraepithelial neoplasia (CIN), or dysplasia. CIN is histologically graded into mild dysplasia (CIN 1), moderate dysplasia (CIN 2), or severe dysplasia (CIN 3). Not all of these lesions progress to invasive cancer; many mild and moderate lesions regress. A further categorization, the Bethesda system, is based on cytologic findings: atypical squamous cells of undetermined significance (ASCUS) or cannot rule out low-grade squamous intraepithelial lesions (LSIL), LSIL (consisting of cytologic atypia and CIN 1), and high-grade squamous intraepithelial lesions (HSIL), primarily CIN 2-3 plus carcinoma in situ.[2]

The rate at which invasive cancer develops from CIN is usually slow, measured in years and perhaps decades.[3] This long natural history provides the opportunity for screening to effectively detect this process during the preinvasive phase, thus allowing early treatment and cure. Because many of these preinvasive lesions (especially LSIL) would have never progressed to invasive cancer,[4,5,6] screening also runs the risk of leading to treatment for women who do not need to be treated.

Human papillomavirus (HPV) is an oncogenic virus and the etiologic agent of cervical cancer and related premalignant disease. HPV is transmitted by sexual contact. Sexually inactive women rarely develop cervical cancer, while sexual activity at an early age with multiple sexual partners is a strong risk factor.[7] Nearly all women with invasive cervical cancer have evidence of HPV infection.[8,9,10,11] Most women with HPV infection, however, never develop cervical cancer; thus this infection is necessary but not sufficient for development of cancer.[12]

Although cervical cancer mortality increases with age,[13] the prevalence of CIN is highest among women in their 20s and 30s. Mortality is rare among women younger than 30 years; HSIL is rare among women older than 65 years who have been previously screened. About 70% of ASCUS and CIN 1 lesions regress within 6 years, while about 6% of CIN 1 lesions progress to CIN 3 or worse. In about 10% to 20% of women with CIN 3 lesions, the lesions progress to invasive cancer.[3,6,14]

Cervical cancer mortality is about 40% higher in black women younger than 65 years than in white women of the same age. Among women older than 65 years, cervical cancer mortality for black women is more than 250% higher than for white women.[15] In either case, mortality is rare among women of any age who have regular screenings.