Performance of high-risk human papillomavirus DNA testing as a primary screen for cervical cancer

A pooled analysis of individual patient data from 17 population-based studies from China

Fang Hui Zhao, Margaret Jane Lin, Feng Chen, Shang Ying Hu, Rong Zhang, Jerome L. Belinson, John W. Sellors, Silvia Franceschi, You Lin Qiao, Philip E. Castle

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Background: Controversy remains over whether high-risk human papillomavirus (HPV) DNA testing should be used as a primary screen for cervical cancer. The aims of our study were to assess whether HPV DNA testing could be applied to cervical-cancer screening programmes in China, as well as other similar developing countries. Methods: We did a pooled analysis of population-based cervical cancer screening studies done in mainland China from 1999 to 2008 with concurrent HPV DNA testing (Hybrid Capture 2 assay; Qiagen, Gaithersburg, MD, USA), liquid-based cytology (LBC), and visual inspection with acetic acid (VIA). Eligible women were sexually active, not pregnant, had an intact uterus, and had no history of cervical intraepithelial neoplasia (CIN), cervical cancer, or pelvic irradiation. All women positive for any test were referred for colposcopy and biopsy. Cervical lesions were diagnosed by directed or random biopsy. We assessed the diagnostic accuracy of HPV DNA testing for the detection of CIN grade 3 or greater. Findings: 30 371 women from 17 cross-sectional, population-based studies in various parts of China were screened. 1523 women were subsequently excluded because of inadequate HPV DNA specimens or they did not have a biopsy taken, which included women with atypical squamous cells of undetermined significance; low-grade squamous intraepithelial lesion or worse; positive HPV, negative cytology, and missing or positive colposcopy results; and unsatisfactory cytology results. HPV DNA testing had a higher sensitivity of 97·5% (95% CI 95·7-98·7) for detection of CIN grade 3 or worse, and a lower specificity of 85·1% (82·3-87·9), compared with cytology (sensitivity 87·9% [95% CI 84·7-90·7], specificity 94·7% [93·5-96·0]) and VIA (54·6% [48·0-61·2], 89·9% [86·8-93·0]). Sensitivity did not vary by study or age (<35 years, 35-49 years, ≥50 years); however, specificity did vary with age (p<0·0001) and was highest in women younger than 35 years (89·4%; 95% CI 86·1-91·5). An increase in the positive cutoff point from the manufacturer recommended 1 pg/mL to 2 pg/mL led to a decrease in the overall HPV DNA positivity from 16·3% to 13·9% (p<0·0001), which could result in a decrease in referral rates, although sensitivity was slightly lower (97·5% to 95·2%). An increase in the cutoff point to 10 pg/mL in women younger than 35 years maintained a high sensitivity 97·7% (95% CI 87·7-99·9) and increased specificity to 93·5% (95% CI 91·9-94·6). Interpretation: HPV DNA testing is highly sensitive and moderately specific for CIN grade 3 or worse, with consistent results across study sites and age groups-including women younger than 35 years. A rise in the cutoff point might be beneficial for future screening programmes in China, especially when screening women younger than 35 years. Funding: Fogarty International Clinical Research Scholars Program (Fogarty International Center, US National Institutes of Health, through the International Clinical Research Fellows Program at Vanderbilt University); Academic Capacity Development Program of the Beijing Municipal Commission of Education; and Cancer Institute and Hospital of the Chinese Academy of Medical Sciences.

Original languageEnglish (US)
Pages (from-to)1160-1171
Number of pages12
JournalThe Lancet Oncology
Volume11
Issue number12
DOIs
StatePublished - Dec 2010
Externally publishedYes

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Uterine Cervical Neoplasms
China
DNA
Cervical Intraepithelial Neoplasia
Population
Cell Biology
Colposcopy
Biopsy
Early Detection of Cancer
Acetic Acid
Enoxacin
Cancer Care Facilities
National Institutes of Health (U.S.)
Research
Developing Countries
Uterus
Referral and Consultation
Age Groups
Education

ASJC Scopus subject areas

  • Oncology

Cite this

Performance of high-risk human papillomavirus DNA testing as a primary screen for cervical cancer : A pooled analysis of individual patient data from 17 population-based studies from China. / Zhao, Fang Hui; Lin, Margaret Jane; Chen, Feng; Hu, Shang Ying; Zhang, Rong; Belinson, Jerome L.; Sellors, John W.; Franceschi, Silvia; Qiao, You Lin; Castle, Philip E.

In: The Lancet Oncology, Vol. 11, No. 12, 12.2010, p. 1160-1171.

Research output: Contribution to journalArticle

Zhao, Fang Hui ; Lin, Margaret Jane ; Chen, Feng ; Hu, Shang Ying ; Zhang, Rong ; Belinson, Jerome L. ; Sellors, John W. ; Franceschi, Silvia ; Qiao, You Lin ; Castle, Philip E. / Performance of high-risk human papillomavirus DNA testing as a primary screen for cervical cancer : A pooled analysis of individual patient data from 17 population-based studies from China. In: The Lancet Oncology. 2010 ; Vol. 11, No. 12. pp. 1160-1171.
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abstract = "Background: Controversy remains over whether high-risk human papillomavirus (HPV) DNA testing should be used as a primary screen for cervical cancer. The aims of our study were to assess whether HPV DNA testing could be applied to cervical-cancer screening programmes in China, as well as other similar developing countries. Methods: We did a pooled analysis of population-based cervical cancer screening studies done in mainland China from 1999 to 2008 with concurrent HPV DNA testing (Hybrid Capture 2 assay; Qiagen, Gaithersburg, MD, USA), liquid-based cytology (LBC), and visual inspection with acetic acid (VIA). Eligible women were sexually active, not pregnant, had an intact uterus, and had no history of cervical intraepithelial neoplasia (CIN), cervical cancer, or pelvic irradiation. All women positive for any test were referred for colposcopy and biopsy. Cervical lesions were diagnosed by directed or random biopsy. We assessed the diagnostic accuracy of HPV DNA testing for the detection of CIN grade 3 or greater. Findings: 30 371 women from 17 cross-sectional, population-based studies in various parts of China were screened. 1523 women were subsequently excluded because of inadequate HPV DNA specimens or they did not have a biopsy taken, which included women with atypical squamous cells of undetermined significance; low-grade squamous intraepithelial lesion or worse; positive HPV, negative cytology, and missing or positive colposcopy results; and unsatisfactory cytology results. HPV DNA testing had a higher sensitivity of 97·5{\%} (95{\%} CI 95·7-98·7) for detection of CIN grade 3 or worse, and a lower specificity of 85·1{\%} (82·3-87·9), compared with cytology (sensitivity 87·9{\%} [95{\%} CI 84·7-90·7], specificity 94·7{\%} [93·5-96·0]) and VIA (54·6{\%} [48·0-61·2], 89·9{\%} [86·8-93·0]). Sensitivity did not vary by study or age (<35 years, 35-49 years, ≥50 years); however, specificity did vary with age (p<0·0001) and was highest in women younger than 35 years (89·4{\%}; 95{\%} CI 86·1-91·5). An increase in the positive cutoff point from the manufacturer recommended 1 pg/mL to 2 pg/mL led to a decrease in the overall HPV DNA positivity from 16·3{\%} to 13·9{\%} (p<0·0001), which could result in a decrease in referral rates, although sensitivity was slightly lower (97·5{\%} to 95·2{\%}). An increase in the cutoff point to 10 pg/mL in women younger than 35 years maintained a high sensitivity 97·7{\%} (95{\%} CI 87·7-99·9) and increased specificity to 93·5{\%} (95{\%} CI 91·9-94·6). Interpretation: HPV DNA testing is highly sensitive and moderately specific for CIN grade 3 or worse, with consistent results across study sites and age groups-including women younger than 35 years. A rise in the cutoff point might be beneficial for future screening programmes in China, especially when screening women younger than 35 years. Funding: Fogarty International Clinical Research Scholars Program (Fogarty International Center, US National Institutes of Health, through the International Clinical Research Fellows Program at Vanderbilt University); Academic Capacity Development Program of the Beijing Municipal Commission of Education; and Cancer Institute and Hospital of the Chinese Academy of Medical Sciences.",
author = "Zhao, {Fang Hui} and Lin, {Margaret Jane} and Feng Chen and Hu, {Shang Ying} and Rong Zhang and Belinson, {Jerome L.} and Sellors, {John W.} and Silvia Franceschi and Qiao, {You Lin} and Castle, {Philip E.}",
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TY - JOUR

T1 - Performance of high-risk human papillomavirus DNA testing as a primary screen for cervical cancer

T2 - A pooled analysis of individual patient data from 17 population-based studies from China

AU - Zhao, Fang Hui

AU - Lin, Margaret Jane

AU - Chen, Feng

AU - Hu, Shang Ying

AU - Zhang, Rong

AU - Belinson, Jerome L.

AU - Sellors, John W.

AU - Franceschi, Silvia

AU - Qiao, You Lin

AU - Castle, Philip E.

PY - 2010/12

Y1 - 2010/12

N2 - Background: Controversy remains over whether high-risk human papillomavirus (HPV) DNA testing should be used as a primary screen for cervical cancer. The aims of our study were to assess whether HPV DNA testing could be applied to cervical-cancer screening programmes in China, as well as other similar developing countries. Methods: We did a pooled analysis of population-based cervical cancer screening studies done in mainland China from 1999 to 2008 with concurrent HPV DNA testing (Hybrid Capture 2 assay; Qiagen, Gaithersburg, MD, USA), liquid-based cytology (LBC), and visual inspection with acetic acid (VIA). Eligible women were sexually active, not pregnant, had an intact uterus, and had no history of cervical intraepithelial neoplasia (CIN), cervical cancer, or pelvic irradiation. All women positive for any test were referred for colposcopy and biopsy. Cervical lesions were diagnosed by directed or random biopsy. We assessed the diagnostic accuracy of HPV DNA testing for the detection of CIN grade 3 or greater. Findings: 30 371 women from 17 cross-sectional, population-based studies in various parts of China were screened. 1523 women were subsequently excluded because of inadequate HPV DNA specimens or they did not have a biopsy taken, which included women with atypical squamous cells of undetermined significance; low-grade squamous intraepithelial lesion or worse; positive HPV, negative cytology, and missing or positive colposcopy results; and unsatisfactory cytology results. HPV DNA testing had a higher sensitivity of 97·5% (95% CI 95·7-98·7) for detection of CIN grade 3 or worse, and a lower specificity of 85·1% (82·3-87·9), compared with cytology (sensitivity 87·9% [95% CI 84·7-90·7], specificity 94·7% [93·5-96·0]) and VIA (54·6% [48·0-61·2], 89·9% [86·8-93·0]). Sensitivity did not vary by study or age (<35 years, 35-49 years, ≥50 years); however, specificity did vary with age (p<0·0001) and was highest in women younger than 35 years (89·4%; 95% CI 86·1-91·5). An increase in the positive cutoff point from the manufacturer recommended 1 pg/mL to 2 pg/mL led to a decrease in the overall HPV DNA positivity from 16·3% to 13·9% (p<0·0001), which could result in a decrease in referral rates, although sensitivity was slightly lower (97·5% to 95·2%). An increase in the cutoff point to 10 pg/mL in women younger than 35 years maintained a high sensitivity 97·7% (95% CI 87·7-99·9) and increased specificity to 93·5% (95% CI 91·9-94·6). Interpretation: HPV DNA testing is highly sensitive and moderately specific for CIN grade 3 or worse, with consistent results across study sites and age groups-including women younger than 35 years. A rise in the cutoff point might be beneficial for future screening programmes in China, especially when screening women younger than 35 years. Funding: Fogarty International Clinical Research Scholars Program (Fogarty International Center, US National Institutes of Health, through the International Clinical Research Fellows Program at Vanderbilt University); Academic Capacity Development Program of the Beijing Municipal Commission of Education; and Cancer Institute and Hospital of the Chinese Academy of Medical Sciences.

AB - Background: Controversy remains over whether high-risk human papillomavirus (HPV) DNA testing should be used as a primary screen for cervical cancer. The aims of our study were to assess whether HPV DNA testing could be applied to cervical-cancer screening programmes in China, as well as other similar developing countries. Methods: We did a pooled analysis of population-based cervical cancer screening studies done in mainland China from 1999 to 2008 with concurrent HPV DNA testing (Hybrid Capture 2 assay; Qiagen, Gaithersburg, MD, USA), liquid-based cytology (LBC), and visual inspection with acetic acid (VIA). Eligible women were sexually active, not pregnant, had an intact uterus, and had no history of cervical intraepithelial neoplasia (CIN), cervical cancer, or pelvic irradiation. All women positive for any test were referred for colposcopy and biopsy. Cervical lesions were diagnosed by directed or random biopsy. We assessed the diagnostic accuracy of HPV DNA testing for the detection of CIN grade 3 or greater. Findings: 30 371 women from 17 cross-sectional, population-based studies in various parts of China were screened. 1523 women were subsequently excluded because of inadequate HPV DNA specimens or they did not have a biopsy taken, which included women with atypical squamous cells of undetermined significance; low-grade squamous intraepithelial lesion or worse; positive HPV, negative cytology, and missing or positive colposcopy results; and unsatisfactory cytology results. HPV DNA testing had a higher sensitivity of 97·5% (95% CI 95·7-98·7) for detection of CIN grade 3 or worse, and a lower specificity of 85·1% (82·3-87·9), compared with cytology (sensitivity 87·9% [95% CI 84·7-90·7], specificity 94·7% [93·5-96·0]) and VIA (54·6% [48·0-61·2], 89·9% [86·8-93·0]). Sensitivity did not vary by study or age (<35 years, 35-49 years, ≥50 years); however, specificity did vary with age (p<0·0001) and was highest in women younger than 35 years (89·4%; 95% CI 86·1-91·5). An increase in the positive cutoff point from the manufacturer recommended 1 pg/mL to 2 pg/mL led to a decrease in the overall HPV DNA positivity from 16·3% to 13·9% (p<0·0001), which could result in a decrease in referral rates, although sensitivity was slightly lower (97·5% to 95·2%). An increase in the cutoff point to 10 pg/mL in women younger than 35 years maintained a high sensitivity 97·7% (95% CI 87·7-99·9) and increased specificity to 93·5% (95% CI 91·9-94·6). Interpretation: HPV DNA testing is highly sensitive and moderately specific for CIN grade 3 or worse, with consistent results across study sites and age groups-including women younger than 35 years. A rise in the cutoff point might be beneficial for future screening programmes in China, especially when screening women younger than 35 years. Funding: Fogarty International Clinical Research Scholars Program (Fogarty International Center, US National Institutes of Health, through the International Clinical Research Fellows Program at Vanderbilt University); Academic Capacity Development Program of the Beijing Municipal Commission of Education; and Cancer Institute and Hospital of the Chinese Academy of Medical Sciences.

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