Determinants of human papillomavirus-negative, low-grade squamous intraepithelial lesions in the atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesions triage study (ALTS).
BACKGROUND
Although low-grade squamous intraepithelial lesions (LSIL) most often are the result of infection by human papillomaviruses (HPV), a small proportion of women with LSIL have negative HPV tests. Using the Atypical Squamous Cells of Undetermined Significance/LSIL Triage Study (ALTS) population, the authors evaluated the significance of HPV-negative LSIL.


METHODS
Women with cytologic interpretations of LSIL by referral Papanicolaou (Pap) tests or enrollment ThinPrep tests (range, 1195-1476 women, depending on the specimen type and the reviewer) had HPV testing performed by both Hybrid Capture 2 and polymerase chain reaction (PCR)-based linear array for 27 HPV types.


RESULTS
Using 4 independent cytologic definitions of LSIL, only 3-11% of women with LSIL were found to have HPV-negative results on both HPV tests. The demographic characteristics of women with HPV-negative LSIL were consistent with those of a low-risk population; many were age > 35 years, and many reported no or only 1 recent sexual partner. The absolute risk of a histologic diagnosis of cervical intraepithelial neoplasia (CIN) Grade 3/carcinoma during the 2-year trial was lower for women with HPV-negative LSIL (range, 2-4%) compared with the absolute risks for oncogenic HPV-positive women with LSIL (range, 13-19%). However, at the next 6-month follow-up visit, 12%-32% of the women with HPV-negative LSIL had a positive HPV test. Finally, visual inspection of cervigrams demonstrated a clear association between a larger os and negative HPV test results compared with women who had HPV-positive LSIL. This may have influenced HPV sample adequacy.


CONCLUSIONS
Based on the ALTS data, the authors found no evidence to support the existence of HPV-negative LSIL as a distinct biologic entity related to the risk of cervical carcinoma. Such results appear to represent cytologic misinterpretations or falsely negative HPV tests.
Pathology Department, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA. rosemary-zuna@ouhsc.edu
Rosemary E
RE
Zuna
Sophia S
SS
Wang
Dorothy L
DL
Rosenthal
Jose
J
Jeronimo
Mark
M
Schiffman
Diane
D
Solomon
D000328:Adult; D000367:Age Factors; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D005188:False Negative Reactions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D065006:Papanicolaou Test; D030361:Papillomavirus Infections / Q000150:complications* / Q000175:diagnosis; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D014218:Triage; D002583:Uterine Cervical Neoplasms / Q000209:etiology* / Q000821:virology; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000473:pathology*
D004279:DNA, Viral