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May 17, 2000

Human Papillomavirus Testing as a Screening Tool for Cervical Cancer

Author Affiliations

Phil B.FontanarosaMD, Deputy EditorIndividualAuthorStephen J.LurieMD, PhD, Contributing EditorIndividualAuthor

JAMA. 2000;283(19):2525-2526. doi:10.1001/jama.283.19.2521

To the Editor: In their study of the utility of testing for high-risk human papillomavirus (HPV) in underprivileged women in rural Costa Rica, Dr Schiffman and colleagues1 suggested that in women older than 35 years, this test is comparable or even superior to the Papanicolaou (Pap) test. The concept of HPV infection as an important factor in the genesis of cancer of the uterine cervix is based on the observation that the DNA of "high risk" viruses is commonly found in nearly all invasive cancers and that viral proteins may impede events in the normal cell cycle.2 The initial theory that the mere presence of high-risk HPV is tantamount to a precancerous or malignant lesion of the uterine cervix is no longer tenable today because of very high rates of transient infections observed in sexually active young women.3 Thus, HPV testing in women aged 18 to 35 years, the age at which most of the important precancerous events occur, would be highly misleading and could result in an inordinately high level of referrals for colposcopy, perhaps as high as 30%. In the study by Schiffman et al, the rate of referral for colposcopy for women aged 18 to 30 years based on HPV testing was 21%, and 11% of women in all age groups had false-positive HPV test results.

Because of the high frequency of HPV infection in younger women, it is now thought that older women with persisting infection with a high-risk virus are at greatest risk for cervical cancer. However, even in this group of women, only a small percentage develop high-grade precancerous lesions.4 Waiting until the age of 35 or 40 years to test for the presence of high-risk HPV infection with some measure of reliability would put the lives of many younger women in serious jeopardy. Schiffman et al found 12 invasive cervical cancers, clearly showing that these women should have been tested many years earlier. Furthermore, to test for persistence of the virus would require 2 or more sequential tests which, in 1 study cited,4 were triggered by high-grade cytologic abnormalities identified in Pap test results. It has been shown that Pap tests not only have a significant false-negative rate5 but that the precise cytologic classification of low-grade vs high-grade lesions is often inaccurate.6

There is little doubt that additional research on the significance of HPV in cervical cancer is warranted, but, in my judgment, there is no evidence that the technique of testing for HPV is currently mature enough to replace the Pap test as a screening test, particularly in younger women who should be the primary target of these efforts. To be sure, the accuracy of the Pap test is far from perfect,5,6 and improvements in its performance would be welcome, but this may require better quality control, additional time needed to screen the material adequately, and better training of cytotechnologists and cytopathologists in the interpretation of this complex test.

Schiffman  MHerrero  RHildesheim  A  et al.  HPV DNA testing in cervical cancer screening: results from women in a high-risk province of Costa Rica.  JAMA. 2000;283:87-93.Google Scholar
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