Am J Clin Pathol 2007;127:335-337 335 335 DOI: 10.1309/RNF3C01JKADQCLKP 335 © American Society for Clinical Pathology AJCP / SPECIAL ARTICLE The Expanded Use of HPV Testing in Gynecologic Practice per ASCCP-Guided Management Requires the Use of Well-Validated Assays Mark H. Stoler, MD, Philip E. Castle, PhD, MPH, Diane Solomon, MD, and Mark Schiffman, MD, MPH DOI: 10.1309/RNF3C01JKADQCLKP In 2001, scientists and clinicians in gynecology and pathol- ogy gathered with the common goals of standardizing and improving the quality of patient care for women with abnormal cervical cytology. The American Society for Colposcopy and Cervical Pathology (ASCCP)-sponsored consensus conference established a series of evidence-based guidelines to help guide clinical practice and management of women with cervical abnormalities. At this time, the value of a large public invest- ment was realized: the National Cancer Institute–sponsored clinical trial called ALTS (ASCUS [atypical squamous cells of undetermined significance] and LSIL [low-grade squamous intraepithelial lesion] Triage Study) firmly established the clin- ical value of human papillomavirus (HPV) testing in the man- agement of patients with equivocal cytologic abnormality. Infection with carcinogenic genotypes of HPV is the necessary cause of cervical cancer 1 and its precursor lesions 2 and, as a corollary, the absence of HPV provides strong reassurance of low cancer risk. To a large extent, the wealth of data generated by ALTS regarding multiple parts of precolposcopic and post- colposcopic management “guided the guidelines” developed by the ASCCP-sponsored consensus conference. These guidelines clarified and simplified management and have been widely adopted. In a commentary accompanying the 2002 JAMA pub- lication of the ASCCP guidelines it was noted 3 : “Human papillomavirus (HPV) testing has matured, appears clinically validated and should become integral to both screening and clinical management…. [The] bar has been raised for bringing forward newer HPV diagnostics. Having well-established positive and negative predictive val- ues for the current [Food and Drug Administration (FDA)- approved] test, which are applicable to most populations, allows for clear probabilistic reporting of the results in direct correlation with those of the source cervical cytology. Any new test must document its performance relative to this stan- dard, because many of the proposed management guidelines are based on the performance data….” Only 1 FDA-approved HPV test was available at the time, although it was widely assumed that the marketplace would rapidly drive the establishment of several newer clinically val- idated HPV tests. In addition to the use of HPV testing in the management of women with abnormal cytology, multiple studies have demonstrated that HPV testing in a primary screening setting is more sensitive, more reproducible, and of better predictive value than cytology alone. When used in combination with cytology, HPV testing compensates for the relative insensitiv- ity of a single Papanicolaou test. 4,5 No detectable high-risk HPV essentially translates to “virtually no risk” of precancer or cancer until the next screening. More than 5 years have passed, and the ASCCP has once again engaged the community to formulate revised guidelines. These guidelines expand the clinical indications for HPV test- ing at additional points in management of cervical abnormali- ties, to identify women at risk for precancer (HPV+) from women (often the majority) who can be safely reassured that they are at virtually no risk for cancer (HPV–). Yet as of this writing, there are still no other FDA-approved HPV tests, although several nonapproved tests are being sold. The lack of multiple, competitive, well-validated tests is a problem, as noted in the new, soon-to-be-published ASCCP guidelines. “These Guidelines expand clinical indications for HPV test- ing based on studies using validated HPV assays. One cannot assume that management decisions that are based on results of HPV tests that have not been similarly validated will result in the by guest on September 23, 2016 http://ajcp.oxfordjournals.org/ Downloaded from