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.
Zuna
Rosemary E
RE
Pathology Department, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA. rosemary-zuna@ouhsc.edu
Wang
Sophia S
SS
Rosenthal
Dorothy L
DL
Jeronimo
Jose
J
Schiffman
Mark
M
Solomon
Diane
D
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