An analysis of high-risk human papillomavirus DNA-negative cervical precancers in the ASCUS-LSIL Triage Study (ALTS)

Philip E. Castle, J. Thomas Cox, Jose Jeronimo, Diane Solomon, Cosette M. Wheeler, Patti E. Gravitt, Mark Schiffman

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

OBJECTIVE: To describe women diagnosed with cervical intraepithelial neoplasia-grade 3 (CIN-3) diagnosed over the 2-year duration of the atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) Triage Study (ALTS) that tested negative for high-risk human papillomavirus (HPV) at enrollment. METHODS: Clinical center pathologists and quality control pathology group reviewed all histology; any CIN-3 diagnosis on biopsy or loop electrosurgical excision procedure (n=621) by at least one pathology review over the duration of ALTS led to inclusion in this analysis. Enrollment cervical specimens were tested for high-risk HPV DNA by two HPV assays; results were combined to minimize simple testing errors. We compared the characteristics of baseline high-risk HPV-negative (n=33) to baseline high-risk HPV-positive (n=588) cumulative diagnosed CIN-3. RESULTS: High-risk HPV-negative CIN-3 cases were less likely to have a second, confirming diagnosis of CIN-3 (24% compared with 56%) by the other pathology group, were more likely to be diagnosed later in follow-up, and more likely to be referred into ALTS because of an ASCUS Pap test rather than an LSIL Pap. Upon review of case histories of the 33 baseline high-risk HPV-negative CIN-3 (5.3% of all cases), there was evidence that these cases were due to incident (new) cases (n=12, 1.9%), non-high-risk HPV (n=5, 0.8%), misclassified histology (n=8, 1.3%), and false-negative high-risk HPV (n=8, 1.3%). CONCLUSION: In any sizeable population, even among women with evidence of cytologic abnormalities, there will be a few cases of cervical precancer that will test high-risk HPV negative for one or more reasons. LEVEL OF EVIDENCE: II.

Original languageEnglish (US)
Pages (from-to)847-856
Number of pages10
JournalObstetrics and Gynecology
Volume111
Issue number4
DOIs
StatePublished - Apr 2008
Externally publishedYes

Fingerprint

Triage
Cervical Intraepithelial Neoplasia
DNA
Pathology
Histology
Atypical Squamous Cells of the Cervix
Squamous Intraepithelial Lesions of the Cervix
Papanicolaou Test
Quality Control
Biopsy
Control Groups

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

An analysis of high-risk human papillomavirus DNA-negative cervical precancers in the ASCUS-LSIL Triage Study (ALTS). / Castle, Philip E.; Cox, J. Thomas; Jeronimo, Jose; Solomon, Diane; Wheeler, Cosette M.; Gravitt, Patti E.; Schiffman, Mark.

In: Obstetrics and Gynecology, Vol. 111, No. 4, 04.2008, p. 847-856.

Research output: Contribution to journalArticle

Castle, Philip E. ; Cox, J. Thomas ; Jeronimo, Jose ; Solomon, Diane ; Wheeler, Cosette M. ; Gravitt, Patti E. ; Schiffman, Mark. / An analysis of high-risk human papillomavirus DNA-negative cervical precancers in the ASCUS-LSIL Triage Study (ALTS). In: Obstetrics and Gynecology. 2008 ; Vol. 111, No. 4. pp. 847-856.
@article{96e98ad2b5b54521a67860709453dc23,
title = "An analysis of high-risk human papillomavirus DNA-negative cervical precancers in the ASCUS-LSIL Triage Study (ALTS)",
abstract = "OBJECTIVE: To describe women diagnosed with cervical intraepithelial neoplasia-grade 3 (CIN-3) diagnosed over the 2-year duration of the atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) Triage Study (ALTS) that tested negative for high-risk human papillomavirus (HPV) at enrollment. METHODS: Clinical center pathologists and quality control pathology group reviewed all histology; any CIN-3 diagnosis on biopsy or loop electrosurgical excision procedure (n=621) by at least one pathology review over the duration of ALTS led to inclusion in this analysis. Enrollment cervical specimens were tested for high-risk HPV DNA by two HPV assays; results were combined to minimize simple testing errors. We compared the characteristics of baseline high-risk HPV-negative (n=33) to baseline high-risk HPV-positive (n=588) cumulative diagnosed CIN-3. RESULTS: High-risk HPV-negative CIN-3 cases were less likely to have a second, confirming diagnosis of CIN-3 (24{\%} compared with 56{\%}) by the other pathology group, were more likely to be diagnosed later in follow-up, and more likely to be referred into ALTS because of an ASCUS Pap test rather than an LSIL Pap. Upon review of case histories of the 33 baseline high-risk HPV-negative CIN-3 (5.3{\%} of all cases), there was evidence that these cases were due to incident (new) cases (n=12, 1.9{\%}), non-high-risk HPV (n=5, 0.8{\%}), misclassified histology (n=8, 1.3{\%}), and false-negative high-risk HPV (n=8, 1.3{\%}). CONCLUSION: In any sizeable population, even among women with evidence of cytologic abnormalities, there will be a few cases of cervical precancer that will test high-risk HPV negative for one or more reasons. LEVEL OF EVIDENCE: II.",
author = "Castle, {Philip E.} and Cox, {J. Thomas} and Jose Jeronimo and Diane Solomon and Wheeler, {Cosette M.} and Gravitt, {Patti E.} and Mark Schiffman",
year = "2008",
month = "4",
doi = "10.1097/AOG.0b013e318168460b",
language = "English (US)",
volume = "111",
pages = "847--856",
journal = "Obstetrics and Gynecology",
issn = "0029-7844",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - An analysis of high-risk human papillomavirus DNA-negative cervical precancers in the ASCUS-LSIL Triage Study (ALTS)

AU - Castle, Philip E.

AU - Cox, J. Thomas

AU - Jeronimo, Jose

AU - Solomon, Diane

AU - Wheeler, Cosette M.

AU - Gravitt, Patti E.

AU - Schiffman, Mark

PY - 2008/4

Y1 - 2008/4

N2 - OBJECTIVE: To describe women diagnosed with cervical intraepithelial neoplasia-grade 3 (CIN-3) diagnosed over the 2-year duration of the atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) Triage Study (ALTS) that tested negative for high-risk human papillomavirus (HPV) at enrollment. METHODS: Clinical center pathologists and quality control pathology group reviewed all histology; any CIN-3 diagnosis on biopsy or loop electrosurgical excision procedure (n=621) by at least one pathology review over the duration of ALTS led to inclusion in this analysis. Enrollment cervical specimens were tested for high-risk HPV DNA by two HPV assays; results were combined to minimize simple testing errors. We compared the characteristics of baseline high-risk HPV-negative (n=33) to baseline high-risk HPV-positive (n=588) cumulative diagnosed CIN-3. RESULTS: High-risk HPV-negative CIN-3 cases were less likely to have a second, confirming diagnosis of CIN-3 (24% compared with 56%) by the other pathology group, were more likely to be diagnosed later in follow-up, and more likely to be referred into ALTS because of an ASCUS Pap test rather than an LSIL Pap. Upon review of case histories of the 33 baseline high-risk HPV-negative CIN-3 (5.3% of all cases), there was evidence that these cases were due to incident (new) cases (n=12, 1.9%), non-high-risk HPV (n=5, 0.8%), misclassified histology (n=8, 1.3%), and false-negative high-risk HPV (n=8, 1.3%). CONCLUSION: In any sizeable population, even among women with evidence of cytologic abnormalities, there will be a few cases of cervical precancer that will test high-risk HPV negative for one or more reasons. LEVEL OF EVIDENCE: II.

AB - OBJECTIVE: To describe women diagnosed with cervical intraepithelial neoplasia-grade 3 (CIN-3) diagnosed over the 2-year duration of the atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) Triage Study (ALTS) that tested negative for high-risk human papillomavirus (HPV) at enrollment. METHODS: Clinical center pathologists and quality control pathology group reviewed all histology; any CIN-3 diagnosis on biopsy or loop electrosurgical excision procedure (n=621) by at least one pathology review over the duration of ALTS led to inclusion in this analysis. Enrollment cervical specimens were tested for high-risk HPV DNA by two HPV assays; results were combined to minimize simple testing errors. We compared the characteristics of baseline high-risk HPV-negative (n=33) to baseline high-risk HPV-positive (n=588) cumulative diagnosed CIN-3. RESULTS: High-risk HPV-negative CIN-3 cases were less likely to have a second, confirming diagnosis of CIN-3 (24% compared with 56%) by the other pathology group, were more likely to be diagnosed later in follow-up, and more likely to be referred into ALTS because of an ASCUS Pap test rather than an LSIL Pap. Upon review of case histories of the 33 baseline high-risk HPV-negative CIN-3 (5.3% of all cases), there was evidence that these cases were due to incident (new) cases (n=12, 1.9%), non-high-risk HPV (n=5, 0.8%), misclassified histology (n=8, 1.3%), and false-negative high-risk HPV (n=8, 1.3%). CONCLUSION: In any sizeable population, even among women with evidence of cytologic abnormalities, there will be a few cases of cervical precancer that will test high-risk HPV negative for one or more reasons. LEVEL OF EVIDENCE: II.

UR - http://www.scopus.com/inward/record.url?scp=41649121450&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41649121450&partnerID=8YFLogxK

U2 - 10.1097/AOG.0b013e318168460b

DO - 10.1097/AOG.0b013e318168460b

M3 - Article

C2 - 18378743

AN - SCOPUS:41649121450

VL - 111

SP - 847

EP - 856

JO - Obstetrics and Gynecology

JF - Obstetrics and Gynecology

SN - 0029-7844

IS - 4

ER -