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

2017; Impact Journals LLC; Volume: 8; Issue: 42 Linguagem: Inglês

10.18632/oncotarget.19783

1949-2553

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

Cervical Cancer and HPV Research

// Ugyen Tshomo 1 , Silvia Franceschi 2 , Tshokey Tshokey 3 , Tashi Tobgay 3 , Iacopo Baussano 2 , Vanessa Tenet 2 , Daniëlle A.M. Heideman 4 , Peter J.F. Snijders 4 and Gary M. Clifford 2 1 Department of Obstetrics & Gynaecology, Jigme Dorji Wangchuck National Referral Hospital, Thimphu, Bhutan 2 International Agency for Research on Cancer, Lyon, France 3 Department of Pathology & Laboratory Medicine, Jigme Dorji Wangchuck National Referral Hospital, Thimphu, Bhutan 4 Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands Correspondence to: Gary M. Clifford, email: cliffordg@iarc.fr Keywords: cytology, methylation, human papillomavirus, cervical cancer, Bhutan Received: January 25, 2017 Accepted: June 26, 2017 Published: August 02, 2017 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+.