Evaluation of cytology versus human papillomavirus-based cervical cancer screening algorithms in Bhutan

Ugyen Tshomo, Silvia Franceschi, Tshokey Tshokey, Tashi Tobgay, Iacopo Baussano, Vanessa Tenet, Daniëlle A M Heideman, Peter J F Snijders, Gary M Clifford

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

To evaluate the performance of existing versus alternative cervical cancer screening protocols in Bhutan, cervical exfoliated cells were collected for cytology and high-risk human papillomavirus (HR-HPV) testing among 1,048 women aged 30-69 years. Conventional smears were prepared and read locally. HR-HPV was tested by GP5+/6+ polymerase chain reaction, followed by genotyping and human DNA methylation analysis among HR-HPV-positives, in Europe. Test positivity was 7.5% for ASCUS or worse (ASCUS+) cytology and 14.0% for HR-HPV. All women with ASCUS+ and/or HR-HPV positivity (n=192) were recalled for colposcopy, among whom a total of 29 cases of histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) were identified. An additional 7 CIN2+ cases were imputed among women without colposcopy. Corrected sensitivities for CIN2+ and CIN3+ were 61% and 74% for ASCUS+, 86% and 96% for HR-HPV, and 47% and 70% for ASCUS+ triage of HR-HPV. Specificity varied from 88% for HR-HPV up to 98% for ASCUS+ triage of HR-HPV, similarly for CIN2+ and CIN3+. Among HR-HPV-positive women with biopsies, methylation analysis offered similar discrimination of CIN2/3 and cervical cancer as ASCUS+, and better than HPV16/18 genotyping alone, but sample sizes were limited. In conclusion, the performance of cytology in Bhutan is in the mid-range of that reported in other screening settings. HR-HPV testing has the potential to improve detection of CIN2+, albeit with a higher referral rate for colposcopy. Cytological triage of HR-HPV-positives (performed in the absence of knowledge of HR-HPV status) reduced referral but missed more than one third of CIN2+.

Original languageEnglish
Pages (from-to)72438-72446
Number of pages9
JournalOncotarget
Volume8
Issue number42
DOIs
Publication statusPublished - 22 Sep 2017

Cite this

Tshomo, U., Franceschi, S., Tshokey, T., Tobgay, T., Baussano, I., Tenet, V., ... Clifford, G. M. (2017). Evaluation of cytology versus human papillomavirus-based cervical cancer screening algorithms in Bhutan. Oncotarget, 8(42), 72438-72446. https://doi.org/10.18632/oncotarget.19783
Tshomo, Ugyen ; Franceschi, Silvia ; Tshokey, Tshokey ; Tobgay, Tashi ; Baussano, Iacopo ; Tenet, Vanessa ; Heideman, Daniëlle A M ; Snijders, Peter J F ; Clifford, Gary M. / Evaluation of cytology versus human papillomavirus-based cervical cancer screening algorithms in Bhutan. In: Oncotarget. 2017 ; Vol. 8, No. 42. pp. 72438-72446.
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abstract = "To evaluate the performance of existing versus alternative cervical cancer screening protocols in Bhutan, cervical exfoliated cells were collected for cytology and high-risk human papillomavirus (HR-HPV) testing among 1,048 women aged 30-69 years. Conventional smears were prepared and read locally. HR-HPV was tested by GP5+/6+ polymerase chain reaction, followed by genotyping and human DNA methylation analysis among HR-HPV-positives, in Europe. Test positivity was 7.5{\%} for ASCUS or worse (ASCUS+) cytology and 14.0{\%} for HR-HPV. All women with ASCUS+ and/or HR-HPV positivity (n=192) were recalled for colposcopy, among whom a total of 29 cases of histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) were identified. An additional 7 CIN2+ cases were imputed among women without colposcopy. Corrected sensitivities for CIN2+ and CIN3+ were 61{\%} and 74{\%} for ASCUS+, 86{\%} and 96{\%} for HR-HPV, and 47{\%} and 70{\%} for ASCUS+ triage of HR-HPV. Specificity varied from 88{\%} for HR-HPV up to 98{\%} for ASCUS+ triage of HR-HPV, similarly for CIN2+ and CIN3+. Among HR-HPV-positive women with biopsies, methylation analysis offered similar discrimination of CIN2/3 and cervical cancer as ASCUS+, and better than HPV16/18 genotyping alone, but sample sizes were limited. In conclusion, the performance of cytology in Bhutan is in the mid-range of that reported in other screening settings. HR-HPV testing has the potential to improve detection of CIN2+, albeit with a higher referral rate for colposcopy. Cytological triage of HR-HPV-positives (performed in the absence of knowledge of HR-HPV status) reduced referral but missed more than one third of CIN2+.",
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Tshomo, U, Franceschi, S, Tshokey, T, Tobgay, T, Baussano, I, Tenet, V, Heideman, DAM, Snijders, PJF & Clifford, GM 2017, 'Evaluation of cytology versus human papillomavirus-based cervical cancer screening algorithms in Bhutan' Oncotarget, vol. 8, no. 42, pp. 72438-72446. https://doi.org/10.18632/oncotarget.19783

Evaluation of cytology versus human papillomavirus-based cervical cancer screening algorithms in Bhutan. / Tshomo, Ugyen; Franceschi, Silvia; Tshokey, Tshokey; Tobgay, Tashi; Baussano, Iacopo; Tenet, Vanessa; Heideman, Daniëlle A M; Snijders, Peter J F; Clifford, Gary M.

In: Oncotarget, Vol. 8, No. 42, 22.09.2017, p. 72438-72446.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Evaluation of cytology versus human papillomavirus-based cervical cancer screening algorithms in Bhutan

AU - Tshomo, Ugyen

AU - Franceschi, Silvia

AU - Tshokey, Tshokey

AU - Tobgay, Tashi

AU - Baussano, Iacopo

AU - Tenet, Vanessa

AU - Heideman, Daniëlle A M

AU - Snijders, Peter J F

AU - Clifford, Gary M

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N2 - To evaluate the performance of existing versus alternative cervical cancer screening protocols in Bhutan, cervical exfoliated cells were collected for cytology and high-risk human papillomavirus (HR-HPV) testing among 1,048 women aged 30-69 years. Conventional smears were prepared and read locally. HR-HPV was tested by GP5+/6+ polymerase chain reaction, followed by genotyping and human DNA methylation analysis among HR-HPV-positives, in Europe. Test positivity was 7.5% for ASCUS or worse (ASCUS+) cytology and 14.0% for HR-HPV. All women with ASCUS+ and/or HR-HPV positivity (n=192) were recalled for colposcopy, among whom a total of 29 cases of histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) were identified. An additional 7 CIN2+ cases were imputed among women without colposcopy. Corrected sensitivities for CIN2+ and CIN3+ were 61% and 74% for ASCUS+, 86% and 96% for HR-HPV, and 47% and 70% for ASCUS+ triage of HR-HPV. Specificity varied from 88% for HR-HPV up to 98% for ASCUS+ triage of HR-HPV, similarly for CIN2+ and CIN3+. Among HR-HPV-positive women with biopsies, methylation analysis offered similar discrimination of CIN2/3 and cervical cancer as ASCUS+, and better than HPV16/18 genotyping alone, but sample sizes were limited. In conclusion, the performance of cytology in Bhutan is in the mid-range of that reported in other screening settings. HR-HPV testing has the potential to improve detection of CIN2+, albeit with a higher referral rate for colposcopy. Cytological triage of HR-HPV-positives (performed in the absence of knowledge of HR-HPV status) reduced referral but missed more than one third of CIN2+.

AB - To evaluate the performance of existing versus alternative cervical cancer screening protocols in Bhutan, cervical exfoliated cells were collected for cytology and high-risk human papillomavirus (HR-HPV) testing among 1,048 women aged 30-69 years. Conventional smears were prepared and read locally. HR-HPV was tested by GP5+/6+ polymerase chain reaction, followed by genotyping and human DNA methylation analysis among HR-HPV-positives, in Europe. Test positivity was 7.5% for ASCUS or worse (ASCUS+) cytology and 14.0% for HR-HPV. All women with ASCUS+ and/or HR-HPV positivity (n=192) were recalled for colposcopy, among whom a total of 29 cases of histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) were identified. An additional 7 CIN2+ cases were imputed among women without colposcopy. Corrected sensitivities for CIN2+ and CIN3+ were 61% and 74% for ASCUS+, 86% and 96% for HR-HPV, and 47% and 70% for ASCUS+ triage of HR-HPV. Specificity varied from 88% for HR-HPV up to 98% for ASCUS+ triage of HR-HPV, similarly for CIN2+ and CIN3+. Among HR-HPV-positive women with biopsies, methylation analysis offered similar discrimination of CIN2/3 and cervical cancer as ASCUS+, and better than HPV16/18 genotyping alone, but sample sizes were limited. In conclusion, the performance of cytology in Bhutan is in the mid-range of that reported in other screening settings. HR-HPV testing has the potential to improve detection of CIN2+, albeit with a higher referral rate for colposcopy. Cytological triage of HR-HPV-positives (performed in the absence of knowledge of HR-HPV status) reduced referral but missed more than one third of CIN2+.

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Tshomo U, Franceschi S, Tshokey T, Tobgay T, Baussano I, Tenet V et al. Evaluation of cytology versus human papillomavirus-based cervical cancer screening algorithms in Bhutan. Oncotarget. 2017 Sep 22;8(42):72438-72446. https://doi.org/10.18632/oncotarget.19783