Human papillomavirus testing following loop electrosurgical excision procedure identifies women at risk for posttreatment cervical intraepithelial neoplasia grade 2 or 3 disease

Aimée R. Kreimer, Richard S. Guido, Diane Solomon, Mark Schiffman, Sholom Wacholder, José Jeronimo, Cosette M. Wheeler, Philip E. Castle

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Abstract

Background: Loop electrosurgical excision procedure (LEEP) is the predominant treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN2+) in the United States, yet following treatment ∼10% of women are diagnosed again with CIN2+, necessitating close follow-up of such patients. Methods: Surveillance strategies using cytology and/or human papillomavirus (HPV) testing were compared among women who underwent LEEP (n = 610) in the Atypical Squamous Cells of Undetermined Significance (ASCUS) Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study. Cervical specimens, collected at 6-month visits for 2 years, were used for cytology, Hybrid Capture 2 (HC2) detection of carcinogenic HPVs, and PCR for genotyping of carcinogenic and noncarcinogenic HPV types. At exit, women had colposcopy for safety and disease ascertainment. Results: At the visit post-LEEP (median time: 4.5 months after LEEP), 36.9% [95% confidence interval (95% CI), 32.7-41.1%] of women were positive for carcinogenic HPV by PCR and 33.7% (95% CI, 29.7-37.9) had ASCUS or more severe (ASCUS+) cytology. The overall 2-year cumulative incidence of histologically confirmed posttreatment CIN2+ was 7.0%; this could be further stratified by the HPV risk category detected at the 6-month visit after LEEP. The 2-year risk associated with HPV16 positivity was 37.0%, significantly higher than for other carcinogenic HPV types (10.8%, P < 0.001), noncarcinogenic types (1.5%, P < 0.001), or testing HPV negative (0%). Post-LEEP cytology (using a positive threshold of ASCUS+) was 78.1% (95% CI, 60.0-90.7%) sensitive for detection of posttreatment CIN2+. By comparison, PCR for carcinogenic HPV and combination testing (using a positive result from carcinogenic HPV testing or cytology as the test threshold with HPV-negative ASCUS not referred) were significantly more sensitive (96.9% for each, P = 0.03); HC2 alone was nonsignificantly more sensitive (90.6%, P = 0.3). Specificity was similar for ASCUS+ cytology (69.1%, 95% CI, 64.6-73.3%) and PCR for carcinogenic HPV (67.1%, P = 0.5), yet was lower for HC2 (63.8%, P = 0.048) and combination testing (62.9%, P = 0.02). Conclusion: Women who tested positive after LEEP for carcinogenic HPV types, especially HPV16, had high risk of subsequent CIN2+. HPV-based detection methods, alone or in combination with cytology, may be useful to incorporate in post-LEEP management strategies.

Original languageEnglish (US)
Pages (from-to)908-914
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume15
Issue number5
DOIs
StatePublished - May 2006
Externally publishedYes

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Cervical Intraepithelial Neoplasia
Cell Biology
Confidence Intervals
Polymerase Chain Reaction
Colposcopy
Triage
Atypical Squamous Cells of the Cervix

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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Human papillomavirus testing following loop electrosurgical excision procedure identifies women at risk for posttreatment cervical intraepithelial neoplasia grade 2 or 3 disease. / Kreimer, Aimée R.; Guido, Richard S.; Solomon, Diane; Schiffman, Mark; Wacholder, Sholom; Jeronimo, José; Wheeler, Cosette M.; Castle, Philip E.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 15, No. 5, 05.2006, p. 908-914.

Research output: Contribution to journalArticle

Kreimer, Aimée R. ; Guido, Richard S. ; Solomon, Diane ; Schiffman, Mark ; Wacholder, Sholom ; Jeronimo, José ; Wheeler, Cosette M. ; Castle, Philip E. / Human papillomavirus testing following loop electrosurgical excision procedure identifies women at risk for posttreatment cervical intraepithelial neoplasia grade 2 or 3 disease. In: Cancer Epidemiology Biomarkers and Prevention. 2006 ; Vol. 15, No. 5. pp. 908-914.
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title = "Human papillomavirus testing following loop electrosurgical excision procedure identifies women at risk for posttreatment cervical intraepithelial neoplasia grade 2 or 3 disease",
abstract = "Background: Loop electrosurgical excision procedure (LEEP) is the predominant treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN2+) in the United States, yet following treatment ∼10{\%} of women are diagnosed again with CIN2+, necessitating close follow-up of such patients. Methods: Surveillance strategies using cytology and/or human papillomavirus (HPV) testing were compared among women who underwent LEEP (n = 610) in the Atypical Squamous Cells of Undetermined Significance (ASCUS) Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study. Cervical specimens, collected at 6-month visits for 2 years, were used for cytology, Hybrid Capture 2 (HC2) detection of carcinogenic HPVs, and PCR for genotyping of carcinogenic and noncarcinogenic HPV types. At exit, women had colposcopy for safety and disease ascertainment. Results: At the visit post-LEEP (median time: 4.5 months after LEEP), 36.9{\%} [95{\%} confidence interval (95{\%} CI), 32.7-41.1{\%}] of women were positive for carcinogenic HPV by PCR and 33.7{\%} (95{\%} CI, 29.7-37.9) had ASCUS or more severe (ASCUS+) cytology. The overall 2-year cumulative incidence of histologically confirmed posttreatment CIN2+ was 7.0{\%}; this could be further stratified by the HPV risk category detected at the 6-month visit after LEEP. The 2-year risk associated with HPV16 positivity was 37.0{\%}, significantly higher than for other carcinogenic HPV types (10.8{\%}, P < 0.001), noncarcinogenic types (1.5{\%}, P < 0.001), or testing HPV negative (0{\%}). Post-LEEP cytology (using a positive threshold of ASCUS+) was 78.1{\%} (95{\%} CI, 60.0-90.7{\%}) sensitive for detection of posttreatment CIN2+. By comparison, PCR for carcinogenic HPV and combination testing (using a positive result from carcinogenic HPV testing or cytology as the test threshold with HPV-negative ASCUS not referred) were significantly more sensitive (96.9{\%} for each, P = 0.03); HC2 alone was nonsignificantly more sensitive (90.6{\%}, P = 0.3). Specificity was similar for ASCUS+ cytology (69.1{\%}, 95{\%} CI, 64.6-73.3{\%}) and PCR for carcinogenic HPV (67.1{\%}, P = 0.5), yet was lower for HC2 (63.8{\%}, P = 0.048) and combination testing (62.9{\%}, P = 0.02). Conclusion: Women who tested positive after LEEP for carcinogenic HPV types, especially HPV16, had high risk of subsequent CIN2+. HPV-based detection methods, alone or in combination with cytology, may be useful to incorporate in post-LEEP management strategies.",
author = "Kreimer, {Aim{\'e}e R.} and Guido, {Richard S.} and Diane Solomon and Mark Schiffman and Sholom Wacholder and Jos{\'e} Jeronimo and Wheeler, {Cosette M.} and Castle, {Philip E.}",
year = "2006",
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T1 - Human papillomavirus testing following loop electrosurgical excision procedure identifies women at risk for posttreatment cervical intraepithelial neoplasia grade 2 or 3 disease

AU - Kreimer, Aimée R.

AU - Guido, Richard S.

AU - Solomon, Diane

AU - Schiffman, Mark

AU - Wacholder, Sholom

AU - Jeronimo, José

AU - Wheeler, Cosette M.

AU - Castle, Philip E.

PY - 2006/5

Y1 - 2006/5

N2 - Background: Loop electrosurgical excision procedure (LEEP) is the predominant treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN2+) in the United States, yet following treatment ∼10% of women are diagnosed again with CIN2+, necessitating close follow-up of such patients. Methods: Surveillance strategies using cytology and/or human papillomavirus (HPV) testing were compared among women who underwent LEEP (n = 610) in the Atypical Squamous Cells of Undetermined Significance (ASCUS) Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study. Cervical specimens, collected at 6-month visits for 2 years, were used for cytology, Hybrid Capture 2 (HC2) detection of carcinogenic HPVs, and PCR for genotyping of carcinogenic and noncarcinogenic HPV types. At exit, women had colposcopy for safety and disease ascertainment. Results: At the visit post-LEEP (median time: 4.5 months after LEEP), 36.9% [95% confidence interval (95% CI), 32.7-41.1%] of women were positive for carcinogenic HPV by PCR and 33.7% (95% CI, 29.7-37.9) had ASCUS or more severe (ASCUS+) cytology. The overall 2-year cumulative incidence of histologically confirmed posttreatment CIN2+ was 7.0%; this could be further stratified by the HPV risk category detected at the 6-month visit after LEEP. The 2-year risk associated with HPV16 positivity was 37.0%, significantly higher than for other carcinogenic HPV types (10.8%, P < 0.001), noncarcinogenic types (1.5%, P < 0.001), or testing HPV negative (0%). Post-LEEP cytology (using a positive threshold of ASCUS+) was 78.1% (95% CI, 60.0-90.7%) sensitive for detection of posttreatment CIN2+. By comparison, PCR for carcinogenic HPV and combination testing (using a positive result from carcinogenic HPV testing or cytology as the test threshold with HPV-negative ASCUS not referred) were significantly more sensitive (96.9% for each, P = 0.03); HC2 alone was nonsignificantly more sensitive (90.6%, P = 0.3). Specificity was similar for ASCUS+ cytology (69.1%, 95% CI, 64.6-73.3%) and PCR for carcinogenic HPV (67.1%, P = 0.5), yet was lower for HC2 (63.8%, P = 0.048) and combination testing (62.9%, P = 0.02). Conclusion: Women who tested positive after LEEP for carcinogenic HPV types, especially HPV16, had high risk of subsequent CIN2+. HPV-based detection methods, alone or in combination with cytology, may be useful to incorporate in post-LEEP management strategies.

AB - Background: Loop electrosurgical excision procedure (LEEP) is the predominant treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN2+) in the United States, yet following treatment ∼10% of women are diagnosed again with CIN2+, necessitating close follow-up of such patients. Methods: Surveillance strategies using cytology and/or human papillomavirus (HPV) testing were compared among women who underwent LEEP (n = 610) in the Atypical Squamous Cells of Undetermined Significance (ASCUS) Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study. Cervical specimens, collected at 6-month visits for 2 years, were used for cytology, Hybrid Capture 2 (HC2) detection of carcinogenic HPVs, and PCR for genotyping of carcinogenic and noncarcinogenic HPV types. At exit, women had colposcopy for safety and disease ascertainment. Results: At the visit post-LEEP (median time: 4.5 months after LEEP), 36.9% [95% confidence interval (95% CI), 32.7-41.1%] of women were positive for carcinogenic HPV by PCR and 33.7% (95% CI, 29.7-37.9) had ASCUS or more severe (ASCUS+) cytology. The overall 2-year cumulative incidence of histologically confirmed posttreatment CIN2+ was 7.0%; this could be further stratified by the HPV risk category detected at the 6-month visit after LEEP. The 2-year risk associated with HPV16 positivity was 37.0%, significantly higher than for other carcinogenic HPV types (10.8%, P < 0.001), noncarcinogenic types (1.5%, P < 0.001), or testing HPV negative (0%). Post-LEEP cytology (using a positive threshold of ASCUS+) was 78.1% (95% CI, 60.0-90.7%) sensitive for detection of posttreatment CIN2+. By comparison, PCR for carcinogenic HPV and combination testing (using a positive result from carcinogenic HPV testing or cytology as the test threshold with HPV-negative ASCUS not referred) were significantly more sensitive (96.9% for each, P = 0.03); HC2 alone was nonsignificantly more sensitive (90.6%, P = 0.3). Specificity was similar for ASCUS+ cytology (69.1%, 95% CI, 64.6-73.3%) and PCR for carcinogenic HPV (67.1%, P = 0.5), yet was lower for HC2 (63.8%, P = 0.048) and combination testing (62.9%, P = 0.02). Conclusion: Women who tested positive after LEEP for carcinogenic HPV types, especially HPV16, had high risk of subsequent CIN2+. HPV-based detection methods, alone or in combination with cytology, may be useful to incorporate in post-LEEP management strategies.

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