Cervical cancer: disparities in screening, treatment, and survival.

Introduction This article will use a case study to review the literature on cervical cancer disparities by race, ethnicity, and socioeconomic status. The patient exemplifies several issues facing underserved populations, including the presence of comorbid diseases, failure to have follow-up visits for colposcopic evaluation and treatment of abnormal Pap smears, and ultimate presentation with invasive cervical cancer. She is unable to keep appointments, receives suboptimal treatment, and is unlikely to be cured of her disease. Case Study. S. R. is a 41-year-old African-American female with a history of schizophrenia. The patient also has a history of abnormal Pap smears and has failed to appear for colposcopy on multiple occasions. Despite many attempts, her medical care providers have been unable to reach the patient, and she ultimately presents to the emergency ward with profuse vaginal bleeding and a hematocrit of 9% (normal: 36–48%). A pelvic examination reveals a large bleeding cervical mass. Emergency biopsy result is consistent with invasive squamous cervical cancer. The patient undergoes emergency radiation treatment and receives multiple blood transfusions. Social Services becomes involved in her care, and she is eventually discharged home in stable condition with a detailed plan for radiation therapy and sensitizing chemotherapy. She completes her radiation treatment after several interruptions but receives less than half of the recommended chemotherapy regimen because of missed appointments. Cervical cancer is now a preventable disease and any woman presenting with invasive cervical cancer should be viewed as a failure of screening. The developing world accounts for 80% of incident cervical cancers, and the disproportionate number of cervical cancer patients can largely be attributed to the lack of organized Pap smear screening programs (1, 2). Despite abundant healthcare resources in the United States, women in minority, socioeconomically disadvantaged, and rural populations have not equally benefited from Pap smear screening (3). HPV Infection and Cervical Neoplasia. HPV has been implicated in the development of virtually all cervical cancers, and HPV DNA is detected in 100% of invasive squamous cervical cancers (4–6). HPVs are classified into high-, intermediate-, and low-risk types based on their association with invasive cancer. Types 16 and 18 are considered high-risk (oncogenic) types and are associated with aggressive forms of cervical cancers (7). Conversely, infection with low-risk HPV subtypes is unlikely to progress to invasive cancer (5). HPV infection is the most common sexually transmitted disease, with reported prevalence rates of 19–46% (8–10). The major risk factor for HPV infection is sexual behavior, including early age at onset of sexual activity, multiple sexual partners, failure to use barrier methods of contraception, and coinfection with other sexually transmitted diseases, particularly HIV (11). The prevalence of HPV positivity declines with increasing age, and persistent infection after age 30 is usually associated with oncogenic types of HPV (12–14). HPV infection disrupts the four-phased cell cycle during which cellular replication occurs. Chromosomal DNA is replicated during the S (synthesis) phase. In the M (mitosis) phase, the separation of duplicated DNA takes place. These two phases are separated by gap phases G1 and G2. Cells that are not dividing exit the cell cycle during the G1 phase and reside in a quiescent state or G0. To replicate, HPV must induce DNA synthesis in host cells in the quiescent phase and move them into an activated G1 phase. The HPV oncogenes, E6 and E7, stimulate cell proliferation by interfering with the functions of the regulatory retinoblastoma protein and the p53 tumor suppressor protein. These cells undergo non-stop proliferation, eventually leading to premalignant changes and malignant transformation. The progression of cellular changes that take place in HPV-infected cells has been described previously (15). The vast majority of HPV infections are transient because the host’s immune response rapidly eliminates the virus. However, women with chronic HPV infection tend to develop cervical abnormalities that progress from mild abnormalities to invasive cancer in susceptible cells of the transformation zone of the cervix (16). The aggressive forms of HPV can dramatically shorten time intervals between infection and neoplasia from years to months. Aggressive forms of HPV infection might also bypass the stages of progression so that invasive cancer arises de novo (14). Determinants of risk for persistent infection and progression to invasive disease are not fully understood. Persistence of infection appears to be related to HPV type and concurrent infection with multiple viral types. As mentioned above, although prevalence of HPV infection is much lower among women over age 30, HPV infections at older ages tend to involve the oncogenic subtypes (16). Furthermore, HPV infection with lower viral load is more likely to persist in older women, suggesting reduced capability to clear the infection. Additionally, these older women are at increased risk for subsequent cervical dysplasia and cancer (10, 17). Reactivation of latent infection can also occur in women ages 55 and older (18). Another cofactor for cervical dysplasia and cancer is HIV infection, which disproportionately affects minority populations in the United States and elsewhere. AIDS induces proAccepted 1/6/03. 1 To whom requests for reprints should be addressed, at Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Biology Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115. E-mail: [email protected]. 2 The abbreviations used are: HPV, human papillomavirus; BACCIS, Breast and Cervical Cancer Intervention Study; NCI, National Cancer Institute. 242s Vol. 12, 242s–247s, March 2003 (Suppl.) Cancer Epidemiology, Biomarkers & Prevention