Role of HPV Type 16 in Cervix and Intraepithelial Neoplasia

At the hospital of ter Harmsel et al, all women who had Pap smears performed in the gynecology department during the years 1988 and 1989 also had screening for HPV 16 infection using PCR technology. Those women who had a positive screen for HPV 16 and had a normal smear were asked to return at six-month intervals for repeat testing. After three consecutive tests had been performed, the study participants were divided into those who had three consecutive HPV 16-positive tests and those who did not.

Of the 5500 women who were screened, 110 (2%) were found to be HPV 16-positive. Thirty-two of these women had an abnormal Pap smear and were excluded. Fifty-four of the remaining 78 women consented to be part of the study. Twenty-five of these 54 had persistent infections, and 29 did not. Eleven of the twenty-five (44%) women with persistent infections developed CIN, whereas only six of the 29 (21%) women who had transient infections did so (P = 0.036). The CIN in those women with persistent infection tended to be more advanced.

In the discussion section of the paper, ter Harmsel et al suggest that women who have positive HPV 16 tests should be monitored more closely because of their increased risk of developing CIN. They further suggest that the routine use of HPV testing would not be cost- effective, even though they used a low estimate of the cost of each HPV test. ter Harmsel et al suggest that women with (atypical squamous cell of undetermined significance) smears might represent a sub-group for whom HPV 16 testing might be cost-effective, but their study did not address this issue.

Comment by Kenneth Noller, MD

Considerable discussion occurs at every cytology meeting, colposcopy meeting, and constantly in the literature regarding the role of HPV testing. There is no doubt that those women who are infected with one of the high-risk virus types (and HPV 16 is by far the most common in the United States) are at higher risk for developing CIN than women who are not infected. Yet, few women who are infected with HPV 16 ever develop detectable CIN. Almost no one would argue for the routine use of HPV 16 testing of all women because it would add an enormous cost to the U.S. health care system. However, there might be a sub-group for whom such testing would be appropriate. For example, ter Harmsel et al suggest that women with ASCUS smears might represent an appropriate sub-group. Presumably, those women with ASCUS smears who were high-risk HPV type positive would continue to be frequently screened. Those who were HPV negative would stop the screenings and return to routine, once yearly Pap smear screening. Indeed, in any algorithm that uses HPV testing, those women who are HPV negative, regardless of their initial status, must be returned to annual screening for the test to be cost-effective.

The controversy will continue probably far into the future. This current article certainly does not help us very much in our clinical practices. Rather, it is an interesting anecdote.

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