Cervical cancer continues to cause significant morbidity and mortality. After breast cancer, cervical cancer is the second most common type of cancer in women worldwide.

Most women with cervical cancer experience a long asymptomatic period before the disease becomes clinically evident. Therefore, early recognition of abnormal cytologic changes through regular screening may prevent progression from preinvasive to invasive disease. Identifying women at risk for developing invasive cervical cancer enables physicians to appropriately select patients who require continual screening rather than annual screening. Women who are at risk for developing cellular abnormalities include those who smoke and those with a history of sexually transmitted diseases, human papillomavirus (HPV) infection, low socioeconomic status, two or more lifetime sexual partners or immunosuppression. The latter factors cause frequent exposure to potential carcinogens, and their requisite presence supports the hypothesis that cervical cancer is a sexually transmitted disease. Smoking also contributes to the development of cervical cancer. While nicotine is not considered a causative agent, smoking may predispose a woman to the development of cervical cancer by lowering her immune surveillance at the cellular level. Smokers also may engage in behaviors that increase their susceptibility to malignant change.

HPV = human papillomavirus.
A preponderance of evidence suggests a causal link between HPV infection and cervical neoplasia. This link is strongest for certain HPV types, particularly types 16 and 18. In a prospective study of 297 women with HPV type 18 and cervical cancer, the relative risk of death was 4.4 times greater in study participants than in women who had tumors associated with a different HPV type. Other subtypes, specifically type 16, are associated with cervical cancer. The HPV subtypes are divided into three categories according to the risk of oncogenesis (Table 1). Other factors, such as smoking, nutrition, coexisting sexually transmitted diseases and genetics, may play a role in a person’s susceptibility to HPV subtypes. The presence of high-risk HPV subtypes is associated with a substantial risk of cancer. The relative risk of malignant transformation of the cervix to high-grade squamous intraepithelial lesion and invasive cancer has been reported to be as high as 296.1 for high-risk HPV subtypes.

Patients with a history of immunosuppression, including human immunodeficiency virus (HIV) infection, require aggressive management; in these patients, cervical disease follows a more severe and prolonged course. Patients with immuno-suppression must deal with persistent infection and the threat of progression to invasive disease. The Centers for Disease Control and Prevention advises all HIV-positive women to receive semiannual screening with a Pap smear during the first year after diagnosis. If no cytologic abnormalities are detected, annual screening is recommended thereafter. Immediate colposcopic examination with colposcopic-directed biopsy is warranted if any cytologic abnormalities are found, including atypical cells of undetermined significance.

Cervical neoplasia represents a spectrum of disease that most commonly affects women during their 40s and 50s. The earliest preinvasive changes, which are squamous intraepithelial lesions, are asymptomatic and usually diagnosed by Pap smear. The intraepithelial neoplasia (mild, moderate or severe) is limited to the cervical epithelium. As invasion occurs, the neoplastic cells penetrate the underlying basement membrane and invade the stroma with the potential for widespread dissemination.

The squamocolumnar junction (SCJ), an area of rapid cell turnover and squamous metaplasia, is the site of this oncogenic transformation. In young women of childbearing age, the SCJ is usually readily visible on the ectocervix. As the cervical epithelium matures, the SCJ may recede within the endocervical canal. This makes the SCJ difficult to visualize and to adequately sample. The importance of adequate sampling of the SCJ in each patient cannot be overemphasized. At the site of metaplastic transformation, the HPV is incorporated into the host DNA, and oncogenesis is initiated.