Five-year risks of CIN 3+ and cervical cancer among women who test pap-negative but are HPV-positive

Hormuzd A. Katki, Mark Schiffman, Philip E. Castle, Barbara Fetterman, Nancy E. Poitras, Thomas Lorey, Li C. Cheung, Tina Raine-Bennett, Julia C. Gage, Walter K. Kinney

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

OBJECTIVE: Current US guidelines for cotesting recommend that the large numbers of women who test Pap-negative, but human papillomavirus (HPV)-positive, return in 1 year, and those who remain HPV-positive or have low-grade squamous intraepithelial lesion (LSIL) or worse Pap results be referred for colposcopy. However, the performance of these guidelines in routine clinical practice has not been evaluated. METHODS: We estimated cumulative 5-year risks of cervical intraepithelial neoplasia grade 3 or worse (CIN 3+) among 32,374 women aged 30 to 64 years with HPV-positive/Pap-negative cotest results at Kaiser Permanente Northern California during 2003 to 2010. RESULTS: The 5-year CIN 3+ risk after an HPV-positive/Pap-negative cotest result, which was found in 3.6% of women, was 4.5% (95% confidence interval [CI] = 4.2%-4.8%). The 5-year cancer risk was 0.34% (95% CI = 0.26%-0.45%), and half of the cases were adenocarcinoma. Overall, 48% of the women remained HPV-positive on return (median = 418 days after baseline), a percentage that varied little over ages 30 to 64 years. At the return after a baseline HPV-positive/Pap-negative result, almost every repeat cotest result predicted greater subsequent 5-year CIN 3+ risk than the same cotest result had at baseline (HPV-positive/LSIL, 9.2% vs 6.1%, p = .01; HPV-positive/atypical squamous cells of undetermined significance [ASC-US], 7.9% vs 6.8%, p = .2; HPV-positive/Pap-negative, 7.4% vs 4.5%, p < .0001; HPV-negative/LSIL,1.7% vs 2.0%, p = .8; HPV-negative/ASC-US, 2.9% vs 0.43%, p = .0005; HPV-negative/Pap-negative, 0.93% vs 0.08%, p < .0001). CONCLUSIONS: Using the principle of "equal management of equal risks," women testing HPV-positive/Pap-negative had a subsequent CIN 3+ risk consistent with risk thresholds for a 1-year return. However, on returning in approximately 1 year, about one-half of women will be referred for colposcopy because of continued HPV positivity or Pap abnormality. Clinicians should keep in mind that cotest results at the return after a baseline HPV-positive/Pap-negative finding are riskier than the same baseline cotest results in the general population, supporting intensified clinical management at return testing.

Original languageEnglish (US)
JournalJournal of Lower Genital Tract Disease
Volume17
Issue number5 SUPPL.1
DOIs
StatePublished - Apr 2013

Fingerprint

Papanicolaou Test
Uterine Cervical Neoplasms
Colposcopy
Guidelines
Confidence Intervals
Cervical Intraepithelial Neoplasia
Risk Management

Keywords

  • Cancer prevention
  • Cervical intraepithelial neoplasia (CIN)
  • Human papillomavirus (HPV)
  • Pap
  • Prospective cohort

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Five-year risks of CIN 3+ and cervical cancer among women who test pap-negative but are HPV-positive. / Katki, Hormuzd A.; Schiffman, Mark; Castle, Philip E.; Fetterman, Barbara; Poitras, Nancy E.; Lorey, Thomas; Cheung, Li C.; Raine-Bennett, Tina; Gage, Julia C.; Kinney, Walter K.

In: Journal of Lower Genital Tract Disease, Vol. 17, No. 5 SUPPL.1, 04.2013.

Research output: Contribution to journalArticle

Katki, HA, Schiffman, M, Castle, PE, Fetterman, B, Poitras, NE, Lorey, T, Cheung, LC, Raine-Bennett, T, Gage, JC & Kinney, WK 2013, 'Five-year risks of CIN 3+ and cervical cancer among women who test pap-negative but are HPV-positive', Journal of Lower Genital Tract Disease, vol. 17, no. 5 SUPPL.1. https://doi.org/10.1097/LGT.0b013e318285437b
Katki, Hormuzd A. ; Schiffman, Mark ; Castle, Philip E. ; Fetterman, Barbara ; Poitras, Nancy E. ; Lorey, Thomas ; Cheung, Li C. ; Raine-Bennett, Tina ; Gage, Julia C. ; Kinney, Walter K. / Five-year risks of CIN 3+ and cervical cancer among women who test pap-negative but are HPV-positive. In: Journal of Lower Genital Tract Disease. 2013 ; Vol. 17, No. 5 SUPPL.1.
@article{a794f20bc4fa44d4bba88d4ec033eea4,
title = "Five-year risks of CIN 3+ and cervical cancer among women who test pap-negative but are HPV-positive",
abstract = "OBJECTIVE: Current US guidelines for cotesting recommend that the large numbers of women who test Pap-negative, but human papillomavirus (HPV)-positive, return in 1 year, and those who remain HPV-positive or have low-grade squamous intraepithelial lesion (LSIL) or worse Pap results be referred for colposcopy. However, the performance of these guidelines in routine clinical practice has not been evaluated. METHODS: We estimated cumulative 5-year risks of cervical intraepithelial neoplasia grade 3 or worse (CIN 3+) among 32,374 women aged 30 to 64 years with HPV-positive/Pap-negative cotest results at Kaiser Permanente Northern California during 2003 to 2010. RESULTS: The 5-year CIN 3+ risk after an HPV-positive/Pap-negative cotest result, which was found in 3.6{\%} of women, was 4.5{\%} (95{\%} confidence interval [CI] = 4.2{\%}-4.8{\%}). The 5-year cancer risk was 0.34{\%} (95{\%} CI = 0.26{\%}-0.45{\%}), and half of the cases were adenocarcinoma. Overall, 48{\%} of the women remained HPV-positive on return (median = 418 days after baseline), a percentage that varied little over ages 30 to 64 years. At the return after a baseline HPV-positive/Pap-negative result, almost every repeat cotest result predicted greater subsequent 5-year CIN 3+ risk than the same cotest result had at baseline (HPV-positive/LSIL, 9.2{\%} vs 6.1{\%}, p = .01; HPV-positive/atypical squamous cells of undetermined significance [ASC-US], 7.9{\%} vs 6.8{\%}, p = .2; HPV-positive/Pap-negative, 7.4{\%} vs 4.5{\%}, p < .0001; HPV-negative/LSIL,1.7{\%} vs 2.0{\%}, p = .8; HPV-negative/ASC-US, 2.9{\%} vs 0.43{\%}, p = .0005; HPV-negative/Pap-negative, 0.93{\%} vs 0.08{\%}, p < .0001). CONCLUSIONS: Using the principle of {"}equal management of equal risks,{"} women testing HPV-positive/Pap-negative had a subsequent CIN 3+ risk consistent with risk thresholds for a 1-year return. However, on returning in approximately 1 year, about one-half of women will be referred for colposcopy because of continued HPV positivity or Pap abnormality. Clinicians should keep in mind that cotest results at the return after a baseline HPV-positive/Pap-negative finding are riskier than the same baseline cotest results in the general population, supporting intensified clinical management at return testing.",
keywords = "Cancer prevention, Cervical intraepithelial neoplasia (CIN), Human papillomavirus (HPV), Pap, Prospective cohort",
author = "Katki, {Hormuzd A.} and Mark Schiffman and Castle, {Philip E.} and Barbara Fetterman and Poitras, {Nancy E.} and Thomas Lorey and Cheung, {Li C.} and Tina Raine-Bennett and Gage, {Julia C.} and Kinney, {Walter K.}",
year = "2013",
month = "4",
doi = "10.1097/LGT.0b013e318285437b",
language = "English (US)",
volume = "17",
journal = "Journal of Lower Genital Tract Disease",
issn = "1089-2591",
publisher = "Lippincott Williams and Wilkins",
number = "5 SUPPL.1",

}

TY - JOUR

T1 - Five-year risks of CIN 3+ and cervical cancer among women who test pap-negative but are HPV-positive

AU - Katki, Hormuzd A.

AU - Schiffman, Mark

AU - Castle, Philip E.

AU - Fetterman, Barbara

AU - Poitras, Nancy E.

AU - Lorey, Thomas

AU - Cheung, Li C.

AU - Raine-Bennett, Tina

AU - Gage, Julia C.

AU - Kinney, Walter K.

PY - 2013/4

Y1 - 2013/4

N2 - OBJECTIVE: Current US guidelines for cotesting recommend that the large numbers of women who test Pap-negative, but human papillomavirus (HPV)-positive, return in 1 year, and those who remain HPV-positive or have low-grade squamous intraepithelial lesion (LSIL) or worse Pap results be referred for colposcopy. However, the performance of these guidelines in routine clinical practice has not been evaluated. METHODS: We estimated cumulative 5-year risks of cervical intraepithelial neoplasia grade 3 or worse (CIN 3+) among 32,374 women aged 30 to 64 years with HPV-positive/Pap-negative cotest results at Kaiser Permanente Northern California during 2003 to 2010. RESULTS: The 5-year CIN 3+ risk after an HPV-positive/Pap-negative cotest result, which was found in 3.6% of women, was 4.5% (95% confidence interval [CI] = 4.2%-4.8%). The 5-year cancer risk was 0.34% (95% CI = 0.26%-0.45%), and half of the cases were adenocarcinoma. Overall, 48% of the women remained HPV-positive on return (median = 418 days after baseline), a percentage that varied little over ages 30 to 64 years. At the return after a baseline HPV-positive/Pap-negative result, almost every repeat cotest result predicted greater subsequent 5-year CIN 3+ risk than the same cotest result had at baseline (HPV-positive/LSIL, 9.2% vs 6.1%, p = .01; HPV-positive/atypical squamous cells of undetermined significance [ASC-US], 7.9% vs 6.8%, p = .2; HPV-positive/Pap-negative, 7.4% vs 4.5%, p < .0001; HPV-negative/LSIL,1.7% vs 2.0%, p = .8; HPV-negative/ASC-US, 2.9% vs 0.43%, p = .0005; HPV-negative/Pap-negative, 0.93% vs 0.08%, p < .0001). CONCLUSIONS: Using the principle of "equal management of equal risks," women testing HPV-positive/Pap-negative had a subsequent CIN 3+ risk consistent with risk thresholds for a 1-year return. However, on returning in approximately 1 year, about one-half of women will be referred for colposcopy because of continued HPV positivity or Pap abnormality. Clinicians should keep in mind that cotest results at the return after a baseline HPV-positive/Pap-negative finding are riskier than the same baseline cotest results in the general population, supporting intensified clinical management at return testing.

AB - OBJECTIVE: Current US guidelines for cotesting recommend that the large numbers of women who test Pap-negative, but human papillomavirus (HPV)-positive, return in 1 year, and those who remain HPV-positive or have low-grade squamous intraepithelial lesion (LSIL) or worse Pap results be referred for colposcopy. However, the performance of these guidelines in routine clinical practice has not been evaluated. METHODS: We estimated cumulative 5-year risks of cervical intraepithelial neoplasia grade 3 or worse (CIN 3+) among 32,374 women aged 30 to 64 years with HPV-positive/Pap-negative cotest results at Kaiser Permanente Northern California during 2003 to 2010. RESULTS: The 5-year CIN 3+ risk after an HPV-positive/Pap-negative cotest result, which was found in 3.6% of women, was 4.5% (95% confidence interval [CI] = 4.2%-4.8%). The 5-year cancer risk was 0.34% (95% CI = 0.26%-0.45%), and half of the cases were adenocarcinoma. Overall, 48% of the women remained HPV-positive on return (median = 418 days after baseline), a percentage that varied little over ages 30 to 64 years. At the return after a baseline HPV-positive/Pap-negative result, almost every repeat cotest result predicted greater subsequent 5-year CIN 3+ risk than the same cotest result had at baseline (HPV-positive/LSIL, 9.2% vs 6.1%, p = .01; HPV-positive/atypical squamous cells of undetermined significance [ASC-US], 7.9% vs 6.8%, p = .2; HPV-positive/Pap-negative, 7.4% vs 4.5%, p < .0001; HPV-negative/LSIL,1.7% vs 2.0%, p = .8; HPV-negative/ASC-US, 2.9% vs 0.43%, p = .0005; HPV-negative/Pap-negative, 0.93% vs 0.08%, p < .0001). CONCLUSIONS: Using the principle of "equal management of equal risks," women testing HPV-positive/Pap-negative had a subsequent CIN 3+ risk consistent with risk thresholds for a 1-year return. However, on returning in approximately 1 year, about one-half of women will be referred for colposcopy because of continued HPV positivity or Pap abnormality. Clinicians should keep in mind that cotest results at the return after a baseline HPV-positive/Pap-negative finding are riskier than the same baseline cotest results in the general population, supporting intensified clinical management at return testing.

KW - Cancer prevention

KW - Cervical intraepithelial neoplasia (CIN)

KW - Human papillomavirus (HPV)

KW - Pap

KW - Prospective cohort

UR - http://www.scopus.com/inward/record.url?scp=84876132391&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876132391&partnerID=8YFLogxK

U2 - 10.1097/LGT.0b013e318285437b

DO - 10.1097/LGT.0b013e318285437b

M3 - Article

VL - 17

JO - Journal of Lower Genital Tract Disease

JF - Journal of Lower Genital Tract Disease

SN - 1089-2591

IS - 5 SUPPL.1

ER -