The Value of Monitoring Human Papillomavirus DNA Results for Papanicolaou Tests Diagnosed As Atypical Squamous Cells of Undetermined Significance: A College of American Pathologists Q-Probes Study of 68 Institutions (Report‪)‬

Human papillomavirus (HPV) has been established as the cause of cervical cancer. (1-3) In the United States, cytologic screening has reduced the incidence of cervical cancer. (4) However, as a result of screening, many women are diagnosed with equivocal Papanicolaou (Pap) test abnormalities, currently categorized by the 2001 Bethesda System Classification as ASC-US (atypical squamous cells). (5) The introduction of liquid-based Pap techniques and the application of HPV DNA testing to the residual sample have dramatically altered the management of women diagnosed with ASC-US. The American Society for Colposcopy and Cervical Pathology recommends reflex high-risk HPV DNA testing for ASC-US Pap test interpretations, and it also recognizes repeat cervical cytologic testing or colposcopy as alternative options. (6) The American Cancer Society supports consideration of the use of HPV DNA testing as an adjunct to cervical cytologic testing or colposcopy as alternative options. (6) The American Cancer Society supports consideration of the use of HPV DNA testing as an adjunct to cervical cytology. (7) The diagnosis of ASC-US reflects a degree of uncertainty in the interpretation of a Pap test. The incidence of cases diagnosed as ASC-US differs dramatically among laboratories, as does the rate of subsequent diagnosis of squamous intraepithelial lesion (SIL) on follow-up biopsies. (8) The interpretation of cervical biopsies also suffers from similar interobserver variation as the interpretation of Pap tests. (9) The application of molecular HPV DNA testing has allowed an objective means to triage patients diagnosed with ASC-US. (10) The percentage of HPV-positive ASC-US cases has been promoted as a quality metric for cytology laboratories. (11,12) However, this rate varies with the threshold of the laboratory in rendering a diagnosis of ASC-US and with the prevalence of HPV infection in the study population. Thus, the utility of this rate as a quality metric remains controversial.