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)

Rosemary E. Zuna, Sophia S. Wang, Dorothy Rosenthal, Jose Jeronimo, Mark Schiffman, Diane Solomon

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)253-262
Number of pages10
JournalCancer
Volume105
Issue number5
DOIs
StatePublished - Oct 25 2005

Fingerprint

Triage
Squamous Intraepithelial Lesions of the Cervix
Atypical Squamous Cells of the Cervix
Carcinoma
Papanicolaou Test
Cervical Intraepithelial Neoplasia
Papillomavirus Infections
Sexual Partners

Keywords

  • Cervical intraepithelial neoplasia
  • Human papillomavirus
  • Hybrid capture 2
  • Low-grade squamous intraepithelial lesions
  • Polymerase chain reaction

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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). / Zuna, Rosemary E.; Wang, Sophia S.; Rosenthal, Dorothy; Jeronimo, Jose; Schiffman, Mark; Solomon, Diane.

In: Cancer, Vol. 105, No. 5, 25.10.2005, p. 253-262.

Research output: Contribution to journalArticle

@article{f90de7b78fbc4da79f50549387f704cd,
title = "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)",
abstract = "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.",
keywords = "Cervical intraepithelial neoplasia, Human papillomavirus, Hybrid capture 2, Low-grade squamous intraepithelial lesions, Polymerase chain reaction",
author = "Zuna, {Rosemary E.} and Wang, {Sophia S.} and Dorothy Rosenthal and Jose Jeronimo and Mark Schiffman and Diane Solomon",
year = "2005",
month = "10",
day = "25",
doi = "10.1002/cncr.21232",
language = "English (US)",
volume = "105",
pages = "253--262",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "5",

}

TY - JOUR

T1 - 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)

AU - Zuna, Rosemary E.

AU - Wang, Sophia S.

AU - Rosenthal, Dorothy

AU - Jeronimo, Jose

AU - Schiffman, Mark

AU - Solomon, Diane

PY - 2005/10/25

Y1 - 2005/10/25

N2 - 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.

AB - 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.

KW - Cervical intraepithelial neoplasia

KW - Human papillomavirus

KW - Hybrid capture 2

KW - Low-grade squamous intraepithelial lesions

KW - Polymerase chain reaction

UR - http://www.scopus.com/inward/record.url?scp=26844550367&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=26844550367&partnerID=8YFLogxK

U2 - 10.1002/cncr.21232

DO - 10.1002/cncr.21232

M3 - Article

C2 - 15991244

AN - SCOPUS:26844550367

VL - 105

SP - 253

EP - 262

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 5

ER -