Screening and Diagnosis
Screening
Pap smear
The paradigm for a cost-effective, easy-to-use, reliable screening test is the cervical cytology screen, or Pap smear. In the United States, the introduction of the Pap smear resulted in a 70% reduction in the incidence of invasive cervical carcinoma between 1955 and the mid-1980s, as well as a shift toward earlier stages at the time of diagnosis. Detection of atypical cells and cervical cancer and its precursor lesions was further improved by the introduction of liquid-based cytologic screening. ThinPrep and SurePath are two currently commercially available liquid-based techniques. Studies have demonstrated that liquid-based cytologic screening has an increased sensitivity in detecting high-grade lesions, a decreased false-negative rate, and a decreased incidence of inadequate samples compared with the conventional Pap test. The ThinPrep Pap Test was also given FDA approval for detection of glandular lesions and adenocarcinoma after studies demonstrated an improved sensitivity in detecting these lesions. The success of cervical cytology, as measured by the lowered incidence of cervical cancer, ironically has led to some controversy regarding the most effective application of this screening tool. With the marked reduction in the incidence of cervical carcinoma, more patients are screened and greater costs incurred to detect each additional case of cervical carcinoma.
HPV DNA testing
The devleopment of molecular-based HPV DNA testing has enhanced cervical cancer screening by identifying women at risk for developing preinvasive cervical lesions and subsequent invasive cancer, thus compensating for the false-negative rates with Pap tests that occur with sampling and detection errors. HPV DNA testing has been shown to have greater sensitivity in detecting preinvasive high-grade cervical lesions. The persistence of high-risk HPV infection contributes to the development of CIN as well as the progression from CIN to cervical cancer. Currently FDA-approved HPV tests include Hybrid Capture 2 (hc2), Cervista HPV HR, and Cervista HPV 16/18 genotyping tests.
Current screening recommendations
The American College of Obstetricians and Gynecologists recently changed its recommendations to start cervical cancer screening for women at the age of 21 regardless of the age of onset of sexual intercourse. For women between the ages of 21 and 29 years, cervical cytology screening is recommended every 2 years with either conventional or liquid-based cytology. Women aged 30 and older who have had three consecutive cervical cytology results that are negative for intraepithelial lesions or malignancy may be tested every 3 years. Screening can be discontinued at either 65 years of age or 70 years of age in women who have three or more negative cytology test results in a row and who have had no abnormal test results in the past 10 years. If screening is discontinued, risk factors should be assessed annually to determine whether reinitiating screening is appropriate. Routine cytologic testing should be discontinued in women who have had a total hysterectomy for benign indications and have no prior history of high-grade CIN. Adjunct HPV testing should not be performed in females younger than 21 years and should not influence management if the test was inadvertently performed. HPV DNA testing should only be used as a triage test to stratify risk to women 21 years and older with a cytology diagnosis of atypical squamous cells of undetermined significance (ASC-US) and postmenopausal women with a cytology diagnosis of low-grade squamous intraepithelial lesion (LSIL). It may be used as an adjunct to cytology for primary screening in women older than 30 years and as a follow-up test after CIN 1 or negative findings on colposcopy in women whose prior cytology diagnosis was ASC-US, ASC-H (atypical squamous cells, cannot rule out high-grade lesion), LSIL, or atypical glandular cells, and in follow-up after treatment for CIN 2 and CIN 3.
In March 2012, the American Cancer Society (ACS) and United States Preventive Service Task Force (USPTF) also released new cervical screening guidelines that recommended against yearly screening. The ACS now recommends that all women start cervical cancer screening at 21 years of age. Women aged 21 to 29 should be screened with conventional cervical cytology smears using liquid-based cytology every 3 years. HPV DNA testing should not be performed in this age-group unless necessary after an abnormal Pap smear. Women aged 30 to 65 should have a Pap smear and HPV testing every 5 years, although testing every 3 years with a Pap smear alone is also acceptable. Women older than 65 years who have had regular screening and normal results should no longer be screened for cervical cancer, while women who have had a diagnosis of cervical cancer or precancerous lesions should continue to be screened. Women who have had a complete hysterectomy (removal of uterus and cervix) and have no history of cervical cancer or precancer should not be screened. Women who received the HPV vaccine should still follow the screening recommendations for their age-group. Women who are at high risk for cervical cancer (ie, those with HIV infection, those who have had organ transplant, or those who were exposed to the drug diethylstilbestrol(Drug information on diethylstilbestrol)) may need to be screened more often. The USPSTF recommendation statement can be accessed at their website.
Diagnosis
The diagnosis of invasive cervical carcinoma can be suggested by either an abnormal Pap smear or an abnormal physical finding.
Colposcopy
In the patient who has an abnormal Pap smear but normal physical findings, colposcopy is indicated. Colposcopic findings consistent with invasive cervical carcinoma include dense white epithelium covering the ectocervix, punctation, mosaicism, and especially, an atypical blood vessel pattern.
Biopsy
If the colposcopic findings are suggestive of invasion, biopsies are obtained from the ectocervix and endocervix. If these biopsies demonstrate only precancerous changes but not an invasive carcinoma, the patient should undergo an excisional biopsy of the cervix. In most current clinical settings, the loop electrosurgical excision procedure is the most expedient method for performing an excisional biopsy. This can be easily accomplished in the office with the patient under local anesthesia and provides adequate tissue for diagnosis. Once the diagnosis of either microinvasive or invasive carcinoma has been established, the patient can be triaged accordingly.
Patient with signs/symptoms of advanced disease
The patient with signs/symptoms of advanced invasive cervical carcinoma requires a cervical biopsy for diagnosis and treatment planning. In this setting, a Pap smear is superfluous and may be misleading.
Pathology
Squamous Cell Carcinoma
The most common histology associated with invasive cervical carcinoma is squamous cell carcinoma, which accounts for approximately 80% of all carcinomas of the uterine cervix. For the most part, the decline in the annual incidence of invasive cervical carcinoma has been seen primarily among patients with this subtype.
Adenocarcinoma
In the past, adenocarcinoma was relatively uncommon as a primary histology of cervical cancer. As a result of the decrease in the overall incidence of invasive squamous cell cancer and, probably, an increase in the baseline incidence of adenocarcinoma of the uterine cervix, this histology now accounts for approximately 20% of all cervical cancers.
There is controversy over whether patients with adenocarcinoma of the cervix have a worse prognosis than those with the more common squamous cell histology. The poorer prognosis associated with adenocarcinoma may be due to the relatively higher frequency of late stage at the time of diagnosis among patients with this histologic type. In several series in which patients were stratified by stage and tumor size, the outcome of cervical adenocarcinoma appeared to be similar to that of squamous lesions of the cervix.
Among the various subtypes of adenocarcinoma, certain types are particularly aggressive and are associated with a poor prognosis. Among them are the small-cell, or neuroendocrine, tumors, which have a poor prognosis even when diagnosed at an early stage.
Rare Tumor Types
More rare lesions of the cervix include lymphoma, sarcoma, and melanoma. These histologic subtypes account for less than 1% of all cervical cancers.
