Why not just continue frequent screening in this less vulnerable population? The consequences of continuing screening in the older, previously well-screened population were nicely illustrated in a study by Sawaya et al,18 using data from the Heart and Estrogen/Progestin Replacement Study (HERS) of postmenopausal women, they evaluated the cytology results of 2,561 women followed over a 4-year period. These women had a Pap test 2 to 2 years after a normal entry cytology.
Subsequent follow-up of cases in which the Pap test was abnormal found only 1 woman with histologic dysplasia, which was a case of mild to moderate dysplasia. To make this diagnosis involved inconvenience, cost and morbidity to the group. To find this single case of mild to moderate dysplasia, 110 women were recalled for follow-ups, which required 231 interventions that included repeat Pap smears, colposcopies, endometrial biopsies, cervical and endocervical biopsies, D&Cs, and excision procedures.
Add to the additional tests, the anxiety inherent in a report of an abnormal Pap test and its follow-up, and the value of limiting screening in this very low risk population become more apparent.
Screen for cervical cancer if there is no cervix?
Since 1996, the US Preventive Services Task Force has recommended against cervical cytology screening in women whose uterus and cervix have been removed for benign indications. Despite this, a recent study showed, as many as 45.6% of such women were still having Pap tests.19
For any screening procedure to be cost effective, there must be a threshold prevalence of the disease in the population to be screened. While women with prior cervical cancer or high-grade dysplasia remain at increased risk for recurrences at the vaginal cuff, women with no history of such disease are at extremely low risk.
In essence, screening in these women becomes a search for primary vaginal cancer, which is one of the rarest of gynecologic malignancies—only 0.3% of cancers in women, a frequency less than that of cancer of the tongue.9 Continued screening in the absence of a cervix implies the need to screen an unacceptably large number of women to diagnose a single lesion. Cytology screening in this group is far more likely to diagnose low-grade vaginal intraepithelial neoplasia (VAIN). VAIN 1 reflects self-limited epithelial changes that are extremely unlikely to progress to cancer.
What is the role of HPV testing?
Last year, the US Food and Drug Administration approved the Hybrid Capture 2 test for high-risk HPV DNA (Digene, Gaithersburg, Md) for use in addition to cervical cytology for screening women over age 30. Both ACOG and the ACS acknowledged this combination of tests as an acceptable option as long as women who test negative on both tests are not retested for 3 years.1,2
Using HPV DNA screening in women under 30 makes little sense. Many studies have confirmed the high prevalence of high-risk HPV in this age group whose risk of invasive cancer is quite low.7,12,20 Screening with HPV before age 30 would result in an unacceptably high false-positive rate, with no advantage over annual screening with cytology alone.
High negative predictive value after age 30
On the other hand, after age 30, as the prevalence of HPV declines, the specificity of this test improves markedly.12 Why wait 3 years before retesting if both tests are negative? The answer lies in the extremely high negative predictive value of the combination. Sherman et al21 determined that the negative predictive value of the combination of cytology plus HPV DNA testing 33 months after both tests are negative is 99.88%. At 45 months, it was still 99.84%.
Thus we can provide excellent assurance to women who test negative that their risk of CIN 3 or squamous cancer is negligible over at least the intervening 3 years.
It’s worth noting that in this same study, the negative predictive value of cytology alone at 33 and 45 months was also quite high: 99.61% and 99.47%, respectively.
ABNORMAL RESULTSConsensus guidelines for combined testing
Management is clear when both tests are negative, or when the Pap shows SIL and the HPV is positive. But what if only 1 of the tests is abnormal? A February 2003 consensus workshop held by ACS, the American Society for Colposcopy and Cervical Pathology, and the National Institutes of Health developed recommendations for managing the various combinations of results.22
ASC-US and positive HPV
Data clearly support triaging these patients to colposcopy. The National Cancer Institute’s ASCUS/LSIL Triage study (ALTS) study showed that, in a group of 1,161 women, this combination of results had a 92% sensitivity for diagnosing CIN 3.23 Solomon Other studies, done under perhaps less rigorous scientific conditions, also showed high sensitivity, though generally not as high as in the ALTS study.