HPV Testing More Accurate Than Pap Smears in Diagnosing Cervical Cancer

When I read a recent article (see: NEJM Report Finds HPV Test More Effective Than Pap in Determining Cervical Cancer Risk), it dawned on my that we may have reached a tipping point in terms of using only morphologic observation as the primary basis for diagnosing malignant lesions. The article focuses on cervical Pap smears and suggests that this technique should not be used as a front-line approach for diagnosing pre-cancerous and cancerous cervical lesions. Here is an excerpt from it (boldface emphasis mine):

The first randomized, controlled study in North America of HPV testing as a stand-alone screen concluded that it is almost 40 percent more accurate than traditional cytology (the Pap "smear") in identifying women with advanced cervical disease, according to a report published ... in The New England Journal of Medicine. The study, which involved more than 10,000 Canadian women age 30-69, found that the HPV test's sensitivity - its ability to accurately identify women with pre-cancerous cervical cells or cancer - was 94.6 percent, compared to 55.4 percent for the Pap. HPV (humanpapilloma virus) is the primary cause of cervical cancer. This seminal study used QAIGEN's Hybrid Capture 2 High-Risk HPV DNA test...."We already knew before conducting this study that the sensitivity of the Pap left a lot to be desired," stated one of the study's authors...."However, 55.4 percent accuracy is only slightly above chance. Flipping a coin gives you 50 percent."...Under the currently recommended guidelines, screening that includes HPV testing may be performed at longer intervals than when the Pap is used alone. However, the authors of the NEJM report concluded that co-testing "only marginally improved sensitivity compared with HPV testing alone". The conclusions of [the study] reinforce a growing number of other studies showing greater sensitivity for HPV testing and suggesting its use as the primary, front-line screen -- with the Pap reserved for follow-up evaluation.

As noted in a previous note (see: Defining Test Sensitivity and Specificity for the General Public), sensitivity is the ability of a test to detect a true positive. The sensitivity of QAIGEN's Hybrid Capture 2 High-Risk HPV DNA test was 94.6% and that of the standard cervical Pap test was little better than a coin flip. The authors of this paper went on to predict that the detection of cervical cancer will henceforth involve consumer education, HPV vaccination, and DNA testing of cervical cells. It appears that we are witnessing the twilight of the cervical Pap smear except for follow-up of patients with diagnosed disease.

For me, the take-home lesson here is that the days are numbered for diagnosing clinically significant lesions only on a morphologic basis. Such observations will need to be correlated with genetic, proteomic, or immunohistochemical analysis of the tissue or cells under review or a search for a viral agent. Surgical pathology is thus becoming more like clinical pathology. It's not clear at this time how many other malignant lesions beyond cervical cancer will be discovered to have a viral or bacterial etiology. Nevertheless, it's clear that major technical and scientific forces are at work that will reshape the practice of surgical and cytopathology.

Comments

[bev M.D.]

Your thoughts about the future of surgical pathology/cytology echo mine precisely. In the future I can even see the entire demise of the surgical pathologist, with specially trained technologists (or even instruments)screening slides to direct further testing, all as part of your "Dept. of Diagnostic Medicine" including the radiologists. I did not find this a personally satisfying career evolution and thus it helped assist my early retirement, although I think every pathologist would agree that it will eventually erase the subjectivity rampant in our specialty.