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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)
Author(s) -
Zuna Rosemary E.,
Wang Sophia S.,
Rosenthal Dorothy L.,
Jeronimo Jose,
Schiffman Mark,
Solomon Diane
Publication year - 2005
Publication title -
cancer cytopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.21232
Subject(s) - medicine , koilocyte , human papillomavirus , squamous intraepithelial lesion , pathology , triage , cancer , cervical intraepithelial neoplasia , cervical cancer , emergency medicine
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. Cancer (Cancer Cytopathol) 2005. Published 2005 American Cancer Society.