Use of human papillomavirus DNA testing to compare equivocal cervical cytologic interpretations in the United States, Scandinavia, and the United Kingdom.
BACKGROUND
Human papillomavirus (HPV) DNA testing may be useful in clarifying equivocal cervical cytologic interpretations. One application might be to standardize the meaning of equivocal interpretations from laboratories in various regions. Because international differences may be particularly marked, international comparisons of emerging data will require clear translations of "equivocal" and similar terms.


METHODS
To perform a three-country comparison, the authors selected a morphologically diverse set of 188 conventional Papanicolaou tests initially classified as "squamous atypia" from a study of more than 20,000 women in Portland, Oregon (1989-1990). Previously, five U.S. expert cytopathologists independently interpreted the slides with screening cytotechnologists' marks in place. For this comparison, one British and two Scandinavian reviewers involved in HPV research reviewed the slides after original marks had been removed. The authors compared all eight reviewers' classifications of negative, equivocal, or abnormal in a series of pairwise comparisons using the kappa statistic. They then compared cytologic interpretations with HPV DNA testing.


RESULTS
Oncogenic HPV DNA detection was significantly associated with increasingly abnormal interpretations for each reader. The British reader tended to rate tests as more abnormal than the American pathologists did, whereas the Scandinavians tended to rate tests as more normal. Reference to the HPV DNA standard clarified the tendency of readers to render systematically more or less severe interpretations. For example, the Scandinavian cytologists discounted subtle (often HPV-associated) changes in favor of cytologic certainty, making HPV triage of equivocal tests less applicable there.


CONCLUSIONS
International research on cytopathology, particularly on the possible uses of HPV DNA testing, will require calibration of local cytologic definitions.
Scott
David R
DR
Kaiser Permanente Department of Pathology, Portland, Oregon, USA.
Hagmar
Bjorn
B
Maddox
Peter
P
Hjerpe
Anders
A
Dillner
Joakim
J
Cuzick
Jack
J
Sherman
Mark E
ME
Stoler
Mark H
MH
Kurman
Robert J
RJ
Kiviat
Nancy B
NB
Manos
M Michele
MM
Schiffman
Mark
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D002138:Calibration; D004279:DNA, Viral / Q000032:analysis*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007391:International Cooperation; D008875:Middle Aged; D015588:Observer Variation; D065006:Papanicolaou Test; D027383:Papillomaviridae / Q000235:genetics* / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000150:complications / Q000175:diagnosis*; D016133:Polymerase Chain Reaction; D012016:Reference Values; D012189:Retrospective Studies; D012537:Scandinavian and Nordic Countries; D014412:Tumor Virus Infections / Q000150:complications / Q000175:diagnosis*; D006113:United Kingdom; D014481:United States; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000821:virology*; D014626:Vaginal Smears
D004279:DNA, Viral