Natural history, incidence, and mortality
In the United States in 2014, it is estimated that 12,360 cases of invasive cervical cancer will be diagnosed and that 4,020 women will die of the disease. These rates had been improving steadily. However, from 2006 to 2010, rates were stable in women younger than 50 years and decreased by 3.1% per year in women aged 50 years and older. From 2006 to 2010, mortality rates were stable among women younger than 50 years, and decreased by 1.2% per year in women aged 50 years and older. 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.
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,[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. 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.