Improved understanding of the central role of human papillomavirus (HPV) in cervical carcinogenesis has led to the development of vaccines and DNA testing for high-risk HPV subtypes. But age-appropriate cytologic screening remains the cornerstone in the prevention and early detection of cervical intraepithelial neoplasia (CIN) and cervical cancer. With prompt diagnosis and treatment of both CIN and early-stage cervical cancer, the prognosis for this disease is excellent.
Cervical cancer is the third most common cancer in women worldwide.1 More than 12,000 women are diagnosed with cervical cancer annually in the United States, with nearly 4,000 cervical cancer deaths reported each year.2-4 Globally, cervical cancer accounts for more than 529,000 new cancer cases and more than 275,000 cancer deaths in women annually, with more than 80% of these cases occurring in developing countries.1,5-7 Over the past 50 years, overall cervical cancer incidence and mortality have declined by more than 70% in the US, largely due to the development of the Papanicolaou screening test (Pap smear).7
Cervical cancer develops from precancerous, or neoplastic, cells of the cervix. Known as cervical intraepithelial neoplasia (CIN), these precancerous lesions are caused by infection with the human papillomavirus (HPV), the main etiologic factor in the development of cervical cancer. The progression from CIN to invasive cervical cancer is typically slow. Because of the long natural history of cervical cancer, screening and preventive measures, when appropriately implemented, can identify precancerous cells before they progress to cervical cancer.
Light micrograph of a "borderline abnormal" cervical smear revealing epithelial cells infected with human papillomavirus.
EPIDEMIOLOGY AND RISK FACTORS
In 2013, approximately 12,340 new cases of cervical cancer will be diagnosed in the US, and 4,030 US women will die as a result of cervical cancer, according to National Cancer Institute estimates.8 Although the incidence rate of cervical cancer in the US has declined significantly, medically underserved populations remain disproportionately affected, with more than 60% of new cases occurring in underserved areas or underscreened populations.6 Epidemiologic studies have also shown higher incidence and mortality among minority populations.9 The incidence of cervical cancer is 30% higher among African American than white women, and the mortality rate is twice as high.9 The incidence of cervical cancer is highest among Hispanics.8
Although many risk factors contribute to the development of cervical cancer, HPV infection is the most important (see Table 12,7,9). HPV has been detected in up to 99% of all invasive cervical cancers, and its presence is necessary for oncogenesis to occur.10 HPV is the most common type of sexually transmitted infection (STI) in the US, with 75% to 80% of sexually active adults acquiring an HPV infection before age 50.11 It is estimated that a woman has a 10% lifetime risk for being infected with HPV, and this risk increases by 15% to 25% with each new sexual partner.7
Studies have shown that cigarette smoking contributes to the development of cervical cancer, with both previous and current smokers having a two- to threefold increased risk for high-grade CIN and cervical cancer, compared with never-smokers.5,9,12 Although the exact cause of this association has not been determined, carcinogens from cigarettes have been found within the cervical mucosa, which may cause alterations in the tissue.2,7
Long-term (≥ 5 years) use of oral contraceptive pills (OCP) by patients with an HPV cervical infection has been established as a risk factor for cervical cancer. It has been shown that the use of OCP causes an increase in HPV gene expression.5 In a study that compared two groups of women who tested positive for HPV DNA, the group that used OCP had a fourfold greater risk for cervical cancer than the group that did not use OCP.2,9,13
Parity, particularly multiparity, and HIV co-infection have also been implicated as risk factors for cervical cancer. The relationship between parity and cervical cancer likely results from the presence of the transformation zone on the ectocervix and increased squamous metaplasia during pregnancy, both of which make cervical tissue more vulnerable to HPV infection.14 HIV co-infection increases the risk for cervical cancer secondary to its immunosuppressive effects; women with both HIV and high-risk HPV infections are four times more likely to develop cervical cancer.15
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