Atypical squamous cells: The case for HPV testing
New data, terminology, and guidelines are in, and human papillomavirus testing is emerging as the most efficient and cost-effective triage option.
No difference for conventional smears. All the advantages of HPV testing in the triage of women with ASC-US persist when the initial referral Pap test is a conventional smear. The only exception is that HPV testing would require the patient to return for a repeat office visit. An alternative would be co-collecting an HPV-test sample at the time of the primary screening Pap test.
One major health-maintenance organization collects a separate sample from all women when the routine conventional Pap test is obtained using a standard Hybrid Capture 2 HPV test kit. The HPV-testing samples are then held until the results of the Pap smear are reported. For women reported to have ASCUS, the samples are sent to the lab for HPV testing; the remaining samples (approximately 95% in most practices) are discarded as medical waste. The cost of each discarded kit is approximately $1. Modeling has found this approach to be cost-effective.19
Postcolposcopy management
Many clinicians are concerned that women referred for the evaluation of HPV-positive ASC-US and found not to have CIN or other manifestations of HPV at colposcopy have a “false-positive” HPV test. However, although there are occasional HPV tests that misclassify a low-risk HPV type as high-risk, actual false-positive tests are very rare.
The 2-year ALTS longitudinal data provide the best information on what to expect when a woman with HPV-positive ASC-US or LSIL is found at colposcopy to have no CIN or to have only CIN 1 that is subsequently managed expectantly.8
The cumulative risk of CIN 2,3 over the 2 years was nearly equivalent for women referred initially for LSIL (27.6%) and for women referred for HPV-positive ASCUS (26.7%), further verifying that management should be similar. Two thirds of the CIN 2,3 was detected at initial colposcopy, and the remaining one third during the postcolposcopy 2-year follow-up.
The risk for subsequent detection of high-grade CIN was nearly identical for all women initially found not to have CIN 2,3 regardless of whether CIN 1 was detected at initial colposcopy, whether the colposcopy was initially completely normal, or whether there were changes that were biopsied and found not to have CIN (risk for CIN 2,3 was 13%, 11.3%, and 11.7% respectively).
Hence, all women referred for evaluation of HPV-positive ASC-US or LSIL and not treated for CIN 2,3 require similar diligent follow-up.
A single HPV test at 12 months detected 92% of all CIN 2,3 found over the 24-month follow-up; 55% tested HPV-positive and were referred to colposcopy.20 Repeat liquid-based cytology at 6 and 12 months referred to colposcopy 63% of women (using a threshold of a repeat Pap test of ASCUS or greater). Cumulative sensitivity of 2 repeat cytologies for CIN 2,3 was slightly less (88%). Combining a repeat Pap test with an HPV test did not increase sensitivity, but did significantly increase referral to colposcopy.
An HPV test alone at 12 months might be the most efficient test for identifying women with CIN 2,3 after colposcopy.20 Further support for this approach can be found in the substantial body of evidence showing that only persistent HPV progresses to CIN 321 and that testing for high-risk HPV detects most CIN 3.4,17,20
The ASCCP guidelines for women referred for either HPV-positive ASC-US or LSIL and found not to have CIN 2,3 or greater at initial colposcopy recommend either HPV testing at 12 months or repeat cytology at 6 and 12 months (FIGURE 1).11,22
Posttreatment follow-up. The ASCCP treatment guidelines also list HPV testing as an acceptable option for follow-up after treatment with cryosurgery, loop electrosurgical excision procedure, laser, or cold-knife conization,22 since there is substantial evidence that women successfully treated for CIN become HPV-negative, whereas women with persistent disease remain HPV-positive.23-25
A posttreatment HPV test should be performed no sooner than 6 months following the procedure, as it takes time for the patient to return to HPV-negative status. A positive HPV test is an indication for colposcopy. However, the guidelines advise against basing repeat treatment on a positive HPV test alone without documentation of persistent CIN.22
Other options for posttreatment surveillance include either repeat cytology or a combination of Pap testing and colposcopy at 4- to 6-month intervals until at least 3 cytologic results are “negative for squamous intraepithelial lesion or malignancy.”22
Annual cytologic follow-up is recommended thereafter. During that follow-up, any abnormal Pap test (ASC-US or greater) should be referred to colposcopy.
Managing ASC-US in special populations
Management of ASC-US may differ from the general recommendations when the patient is postmenopausal or immunosuppressed. However, there are no differences in the management guidelines during pregnancy.
