Relative Performance of HPV and Cytology Components of Cotesting in Cervical Screening

Mark Schiffman, Walter K. Kinney, Li C. Cheung, Julia C. Gage, Barbara Fetterman, Nancy E. Poitras, Thomas S. Lorey, Nicolas Wentzensen, Brian Befano, John Schussler, Hormuzd A. Katki, Philip E. Castle

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background: The main goal of cervical screening programs is to detect and treat precancer before cancer develops. Human papillomavirus (HPV) testing is more sensitive than cytology for detecting precancer. However, reports of rare HPV-negative, cytology-positive cancers are motivating continued use of both tests (cotesting) despite increased testing costs. Methods: We quantified the detection of cervical precancer and cancer by cotesting compared with HPV testing alone at Kaiser Permanente Northern California (KPNC), where 1 208 710 women age 30 years and older have undergone triennial cervical cotesting since 2003. Screening histories preceding cervical cancers (n = 623) and precancers (n = 5369) were examined to assess the relative contribution of the cytology and HPV test components in identifying cases. The performances of HPV testing and cytology were compared using contingency table methods, general estimating equation models, and nonparametric statistics; all statistical tests were two-sided. Results: HPV testing identified more women subsequently diagnosed with cancer (P < .001) and precancer (P < .001) than cytology. HPV testing was statistically significantly more likely to be positive for cancer at any time point (P < .001), except within 12 months (P = .10). HPV-negative/cytology-positive results preceded only small fractions of cases of precancer (3.5%) and cancer (5.9%); these cancers were more likely to be regional or distant stage with squamous histopathology than other cases. Given the rarity of cancers among screened women, the contribution of cytology to screening translated to earlier detection of at most five cases per million women per year. Two-thirds (67.9%) of women found to have cancer during 10 years of follow-up at KPNC were detected by the first cotest performed. Conclusions: The added sensitivity of cotesting vs HPV alone for detection of treatable cancer affected extremely few women.

Original languageEnglish (US)
Pages (from-to)501-508
Number of pages8
JournalJournal of the National Cancer Institute
Volume110
Issue number5
DOIs
StatePublished - May 1 2018

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Cell Biology
Neoplasms
Uterine Cervical Neoplasms
Nonparametric Statistics
Costs and Cost Analysis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Relative Performance of HPV and Cytology Components of Cotesting in Cervical Screening. / Schiffman, Mark; Kinney, Walter K.; Cheung, Li C.; Gage, Julia C.; Fetterman, Barbara; Poitras, Nancy E.; Lorey, Thomas S.; Wentzensen, Nicolas; Befano, Brian; Schussler, John; Katki, Hormuzd A.; Castle, Philip E.

In: Journal of the National Cancer Institute, Vol. 110, No. 5, 01.05.2018, p. 501-508.

Research output: Contribution to journalArticle

Schiffman, M, Kinney, WK, Cheung, LC, Gage, JC, Fetterman, B, Poitras, NE, Lorey, TS, Wentzensen, N, Befano, B, Schussler, J, Katki, HA & Castle, PE 2018, 'Relative Performance of HPV and Cytology Components of Cotesting in Cervical Screening', Journal of the National Cancer Institute, vol. 110, no. 5, pp. 501-508. https://doi.org/10.1093/jnci/djx225
Schiffman, Mark ; Kinney, Walter K. ; Cheung, Li C. ; Gage, Julia C. ; Fetterman, Barbara ; Poitras, Nancy E. ; Lorey, Thomas S. ; Wentzensen, Nicolas ; Befano, Brian ; Schussler, John ; Katki, Hormuzd A. ; Castle, Philip E. / Relative Performance of HPV and Cytology Components of Cotesting in Cervical Screening. In: Journal of the National Cancer Institute. 2018 ; Vol. 110, No. 5. pp. 501-508.
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abstract = "Background: The main goal of cervical screening programs is to detect and treat precancer before cancer develops. Human papillomavirus (HPV) testing is more sensitive than cytology for detecting precancer. However, reports of rare HPV-negative, cytology-positive cancers are motivating continued use of both tests (cotesting) despite increased testing costs. Methods: We quantified the detection of cervical precancer and cancer by cotesting compared with HPV testing alone at Kaiser Permanente Northern California (KPNC), where 1 208 710 women age 30 years and older have undergone triennial cervical cotesting since 2003. Screening histories preceding cervical cancers (n = 623) and precancers (n = 5369) were examined to assess the relative contribution of the cytology and HPV test components in identifying cases. The performances of HPV testing and cytology were compared using contingency table methods, general estimating equation models, and nonparametric statistics; all statistical tests were two-sided. Results: HPV testing identified more women subsequently diagnosed with cancer (P < .001) and precancer (P < .001) than cytology. HPV testing was statistically significantly more likely to be positive for cancer at any time point (P < .001), except within 12 months (P = .10). HPV-negative/cytology-positive results preceded only small fractions of cases of precancer (3.5{\%}) and cancer (5.9{\%}); these cancers were more likely to be regional or distant stage with squamous histopathology than other cases. Given the rarity of cancers among screened women, the contribution of cytology to screening translated to earlier detection of at most five cases per million women per year. Two-thirds (67.9{\%}) of women found to have cancer during 10 years of follow-up at KPNC were detected by the first cotest performed. Conclusions: The added sensitivity of cotesting vs HPV alone for detection of treatable cancer affected extremely few women.",
author = "Mark Schiffman and Kinney, {Walter K.} and Cheung, {Li C.} and Gage, {Julia C.} and Barbara Fetterman and Poitras, {Nancy E.} and Lorey, {Thomas S.} and Nicolas Wentzensen and Brian Befano and John Schussler and Katki, {Hormuzd A.} and Castle, {Philip E.}",
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AU - Schiffman, Mark

AU - Kinney, Walter K.

AU - Cheung, Li C.

AU - Gage, Julia C.

AU - Fetterman, Barbara

AU - Poitras, Nancy E.

AU - Lorey, Thomas S.

AU - Wentzensen, Nicolas

AU - Befano, Brian

AU - Schussler, John

AU - Katki, Hormuzd A.

AU - Castle, Philip E.

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N2 - Background: The main goal of cervical screening programs is to detect and treat precancer before cancer develops. Human papillomavirus (HPV) testing is more sensitive than cytology for detecting precancer. However, reports of rare HPV-negative, cytology-positive cancers are motivating continued use of both tests (cotesting) despite increased testing costs. Methods: We quantified the detection of cervical precancer and cancer by cotesting compared with HPV testing alone at Kaiser Permanente Northern California (KPNC), where 1 208 710 women age 30 years and older have undergone triennial cervical cotesting since 2003. Screening histories preceding cervical cancers (n = 623) and precancers (n = 5369) were examined to assess the relative contribution of the cytology and HPV test components in identifying cases. The performances of HPV testing and cytology were compared using contingency table methods, general estimating equation models, and nonparametric statistics; all statistical tests were two-sided. Results: HPV testing identified more women subsequently diagnosed with cancer (P < .001) and precancer (P < .001) than cytology. HPV testing was statistically significantly more likely to be positive for cancer at any time point (P < .001), except within 12 months (P = .10). HPV-negative/cytology-positive results preceded only small fractions of cases of precancer (3.5%) and cancer (5.9%); these cancers were more likely to be regional or distant stage with squamous histopathology than other cases. Given the rarity of cancers among screened women, the contribution of cytology to screening translated to earlier detection of at most five cases per million women per year. Two-thirds (67.9%) of women found to have cancer during 10 years of follow-up at KPNC were detected by the first cotest performed. Conclusions: The added sensitivity of cotesting vs HPV alone for detection of treatable cancer affected extremely few women.

AB - Background: The main goal of cervical screening programs is to detect and treat precancer before cancer develops. Human papillomavirus (HPV) testing is more sensitive than cytology for detecting precancer. However, reports of rare HPV-negative, cytology-positive cancers are motivating continued use of both tests (cotesting) despite increased testing costs. Methods: We quantified the detection of cervical precancer and cancer by cotesting compared with HPV testing alone at Kaiser Permanente Northern California (KPNC), where 1 208 710 women age 30 years and older have undergone triennial cervical cotesting since 2003. Screening histories preceding cervical cancers (n = 623) and precancers (n = 5369) were examined to assess the relative contribution of the cytology and HPV test components in identifying cases. The performances of HPV testing and cytology were compared using contingency table methods, general estimating equation models, and nonparametric statistics; all statistical tests were two-sided. Results: HPV testing identified more women subsequently diagnosed with cancer (P < .001) and precancer (P < .001) than cytology. HPV testing was statistically significantly more likely to be positive for cancer at any time point (P < .001), except within 12 months (P = .10). HPV-negative/cytology-positive results preceded only small fractions of cases of precancer (3.5%) and cancer (5.9%); these cancers were more likely to be regional or distant stage with squamous histopathology than other cases. Given the rarity of cancers among screened women, the contribution of cytology to screening translated to earlier detection of at most five cases per million women per year. Two-thirds (67.9%) of women found to have cancer during 10 years of follow-up at KPNC were detected by the first cotest performed. Conclusions: The added sensitivity of cotesting vs HPV alone for detection of treatable cancer affected extremely few women.

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