Natural History, Incidence, and Mortality
In the United States in 2009, it is estimated that 11,270 cases of invasive cervical cancer will be diagnosed and that 4,070 women will die of the disease. These rates have been improving steadily, with a 70% drop between 1950 and 1970 and a 40% drop between 1970 and 1999. This improvement has been attributed largely to screening with the Papanicolaou 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.
The rate at which invasive cancer develops from CIN is usually slow, measured in years and perhaps decades. 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,[5,6,7] screening also runs the risk of leading to treatment of women who do not need to be treated.
The leading etiologic factor in the development of preinvasive and invasive cervical cancer is infection with specific types of human papillomavirus (HPV), which is transmitted by sexual contact. Thus, sexually inactive women rarely develop cervical cancer, while sexual activity at an early age with multiple sexual partners is a strong risk factor. About 95% of women with invasive cervical cancer have evidence of HPV infection.[8,9,10,11] Many women with HPV infection, however, never develop cervical cancer; thus this infection is necessary but not sufficient for development of cancer.
Although cervical cancer mortality increases with age (maximum mortality for white women is between the ages of 45 years and 70 years; for black women it is in their 70s), 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. About 10% to 20% of women with CIN 3 lesions progress to invasive cancer.[4,7,13]