Invasive cancer of the uterine cervix is either the leading or second leading cause of death from cancer among women worldwide and is the leading cause of death from cancer among women in developing countries. In some developing countries in the age group of 35 to 45, it is the leading cause of death from any cause. There are approximately 450,000 new cases of cervical cancer annually worldwide, compared to 13,500 new cases in the United States and 4,500 annual deaths.
It is widely recognized that cervical intraepithelial neoplasia (CIN) is a precursor to invasive squamous cell cancers and that adenocarcinoma in-situ is a precursor to invasive endocervical adenocarcinomas, but there are few reliable data on the number of new cases of these precursor lesions that are detected in most populations.
Screening
In the US, screening is performed almost exclusively using exfoliative cytology. In general, it is recommended that screening be initiated with onset of sexual activity and that, after three consecutive annual negative Papanicolaou tests, the subsequent screening interval be chosen by the patient and physician. For all practical purposes, this has translated into an annual recommendation.
The Papanicolaou smear should always include both an endocervical sample taken using a specialized brush device and a scraping sample from the immature transformation zone, including the present squamocolumnar junctions. Recent economic pressures have led to combining these samples on a single slide. There is no apparent loss in the detection efficiency when a one-slide technique is used. The specimen must be fixed immediately in order to avoid air-drying artifact.
Bethesda Classification of Cervical CytologyThe terminology for reporting the results of the Papanicolaou (Pap) smear interpretation generally follows the Bethesda System (TBS) nomenclature (Table 1). A statement of adequacy is important, and smears are classified as within normal limits if no abnormalities are detected. If abnormal cells are seen and they are characteristic of an human papillomavirus (HPV)-related lesion of the squamous epithelium, they are generally referred to as being consistent with the presence of a squamous intraepithelial lesion (SIL) and further stratified as being low-grade or high-grade. This is in keeping with the molecular evidence that squamous cell cancer precursors are best classified in a two-tiered system. Smears that contain cells that are abnormal but not readily classified are generally diagnosed as having atypical squamous cells of undetermined significance (ASCUS) and further subclassified as to the most likely lesion to be present. Invasive cancers, metastatic disease, and other neoplasms are classified appropriately.
Although there have been problems relating to the introduction of TBS in the United States, it is the dominant system of the nomenclature and brings a uniform language to a previously fragmented nomenclature, although variations are becoming apparent. False-negative Pap smears are inevitable and occur even in the most highly capable laboratories with extensive quality-control systems in place. A negative smear never rules out the presence of neoplasia, and patients with signs or symptoms that could be attributable to cervical neoplasia should be examined and neoplasia excluded.
Screening for cervical neoplasia with the Pap smear is the most cost-effective cancer reduction program yet devised. In all populations in which it has been studied adequately, it has been reported that there is a direct relationship between the proportion of the population screened and a decline in the incidence of cervical cancer and deaths from cervical cancer. It is clear that screening should be used in all at-risk populations if the resources are available to undertake such a program.
A number of potentially useful alternate or complementary screening techniques are being developed, including computer-analyzed Pap smears and HPV DNA typing. These new techniques have the potential to lower the false-negative rate, lower the cost of screening, or increase the screening interval. More data are needed before these adjuncts gain wider acceptance.
Diagnosis
The diagnosis of invasive cervical carcinoma requires microscopic examination of tissue. Cytology and colposcopy are not diagnostic, although each is extremely important in the diagnostic process. Once cytology has indicated the presence of cells suspicious for invasive disease and no lesion is visible, colposcopy is invaluable in finding the area to be biopsied for proof of invasion. Endocervical and endometrial sampling are important in the absence of colposcopic lesions.
The initial work-up of invasive cervical cancer patients includes a history and physical examination, chest radiography, intravenous pyelogram (IVP) or computed tomography (CT) scan, cystoscopy/proctosigmoidoscopy, and HIV testing (especially for the younger, at-risk patient). In microinvasive disease, IVP or CT scan is done selectively, and some centers do not routinely employ IVP/CT or cystoscopy/proctosigmoidoscopy for early stage I disease (less than 2 to 3 cm) because of relatively low yield. During the last decade, however, CT scan has become increasingly popular in the work-up and management of cervical cancer. Several authors have suggested its use in clinical staging; however, there are important limitations with its use. It has been found that CT scans are unreliable in detecting subclinical parametrial disease and nodal metastasis less than 2 cm in diameter. In patients who are not candidates for surgical staging, CT scan can be helpful in assessing nodal disease. All enlarged lymph nodes should be studied histologically/cytologically by either surgical excision or fine-needle aspiration because of the 5% to 10% false-positive rate of CT.
Recently, magnetic resonance imaging has emerged as a radiologic modality capable of detecting early parametrial and nodal disease. Further experience is needed to establish its role and cost-effectiveness in the work-up and management of cervical carcinoma. Because of infrequent colon involvement, the use of barium enema should be restricted to symptomatic patients. Routine bone scan is unproductive unless the patient complains of bone pain.
