Since its adoption in the United States in the 1940s, universal screening using the Papanicolaou (Pap) test has decreased death from cervical cancer by more than 70%. Cervical cancer screening is the most successful cancer screening program in history. Although the Pap smear has reduced cervical cancer deaths in the United States, many challenges remain.The most significant barrier is lack of compliance with screening recommendations, particularly in older women , the uninsured, ethnic minorities, and women in rural areas. In the United States, 50% to 70% of cervical cancer cases occur among women who have never been screened or who have not been screened within the past 5 years. Signifi cant racial disparity exists in both incidence and death from cervical cancer, with the highest-risk ethnic group being Vietnamese women. Although cervical cancer accounts for only 2% of all cancer
deaths in women, it ranks second among women aged 20 to 39 years.
deaths in women, it ranks second among women aged 20 to 39 years.
Prevention of cervical cancer and cervical cancer mortality is feasible because (1) progression from early cellular abnormalities, termed low-grade dysplasia (LGSIL), through more severe dysplasia (high-grade dysplasia [HGSIL]), to carcinoma in situ (CIS) and invasive cancer is generally slow, allowing time for detection; (2) associated cellular abnormalities can be identifi ed; and (3) eff ective treatment is available for premalignant lesions. Although screening has been successful in reducing squamous cancer incidence and mortality, the
incidence of glandular or adenocarcinoma is increasing.
Etiology and Pathogenesis
Most cervical cancer develops within the cervical transformation zone, the region where the epithelial cells of the cervix and vagina undergo metaplastic transformation to the columnar epithelium that lines the endocervical glands. Demonstrates the findings in this area, visualized during colposcopy. The susceptibility of women to squamous cancer is due to the fragility of this tissue in combination with its direct exposure to environmental carcinogens, the most important being the human papilloma virus (HPV). HPV plays a central role in the development of cervical cancer. Ninety-five percent to 99% of squamous cell cervical cancers and 75% to 95% of high-grade CIN lesions have detectable HPV DNA. HPV is transmitted primarily by sexual intercourse and can persist in vulvar, vaginal, and cervical tissue throughout a woman’s lifetime. As a group of more than 100 viral types, HPV viruses cause a diverse spectrum of diseases. HPV types 6 and 11 cause warts, and types 16 and 18 cause cancer. Among women without cervical cytology abnormalities at baseline, those with high-risk HPV types have a relative risk for developing high-grade cervical lesions that is 58- to 71-fold higher than those without detectable HPV. HPV DNA must integrate into the host genomic DNA to promote the changes that lead to cervical cancer. This event appears to be rare, but it is essential for cancer progression. In the absence of viral integration, the normal viral life cycle produces morphologic changes in the cervical epithelium characteristic of LGSIL. With viral integration, cellular changes characteristic of HGSIL and ultimately cancer are observed (Fig. 85-2). Interrelated host factors such as age, nutritional status, immune function, smoking, and possibly silent genetic polymorphisms
modulate incorporation of viral DNA. It is estimated that nearly 100% of CIS and cancer lesions have integrated HPV DNA compared with a small minority of low-grade dysplastic lesions. The transition time from simple viral infection to integration of DNA and oncogenesis is unknown and may be influenced by the patient’s risk profile. Natural history studies confirm that, in most cases, the course of infection and cervical abnormalities progress in an orderly fashion from less to more severe lesions. Thus, the sequence of changes associated with HPV infection and the development of cervical cancer parallel the cytologic changes observed and are amenable to surveillance with Pap tests. In the United States, peak incidence and prevalence of HPV infection occurs among women younger than 25 years; however, more than 30% of postmenopausal women have detectable HPV DNA using polymerase chain reaction detection methods. Because most cervical cancers are associated with HPV infection, independent of age of cancer incidence, screening for epithelial changes caused by the virus is indicated in all age groups.
Cervical cancer develops a clinically visible lesion when invasive, and, when deeply invasive, it spreads by local extension, through lymphatics or the bloodstream Preinvasive cervical neoplasias are rarely associated with symptoms. With progression to invasive cervical cancer, women are more likely to complain of abnormal vaginal discharge and intermenstrual bleeding, specifically after douching or coitus. Pain, loss of appetite, and weight loss are all late manifestations. Back pain may indicate ureteral obstruction related to pelvic sidewall involvement by tumor. Involvement of the bladder or rectum may present with bleeding as well as fistula formation.
Many cervical conditions, including genital tract infection, can influence Pap test interpretation and may result in false-positive findings. Certain benign conditions such as leiomyomas, primary herpes infection, endometriosis, and cervical polyps can cause a palpable or visible cervical mass. Uterine cancer can extend to the cervix and vagina and needs to be considered in the differential diagnosis.
Management and Therapy
Pap test screening is recommended in women who are sexually active or age 18 or older. After three or more consecutive annual examinations with normal findings, the Pap test may be performed less frequently at the discretion of the physician. In asymptomatic women who have undergone hysterectomy and who do not have a history of genital dysplasia or cancer, Pap tests are not necessary. Conventional Triage of Abnormal
Treatment and management of screening cytologic abnormalities begins with referral to a specialist trained in colposcopy and therapy of preinvasive cervical dysplasia. Documented cases of invasive cervical cancer should be referred to a gynecologic oncologist. Understanding the triage of abnormal Pap tests requires an understanding of the current Bethesda classification of Pap test abnormalities. Women with two atypical squamous cells of undetermined significance (ASCUS) or LGSIL Pap tests should undergo colposcopy and directed biopsy. A single HGSIL or cancer Pap test should prompt immediate referral for colposcopic evaluation. Whenever a clinically suspicious lesion or ulceration of the cervix is observed, referral for examination with colposcopy and biopsy should occur, irrespective of the Pap test result. Colposcopy includes magnified examination of the cervix after the application of dilute acetic acid, which accentuates dysplastic epithelium by turning it white. Directed punch biopsies of the cervix of all acetowhite lesions and any ulcerative areas showing atypical vascular patterns are performed to determine which patients require treatment and which require routine or close follow-up.