Details

Autor(en) / Beteiligte

• Cook, Darrel A.
• Krajden, Mel
• Brentnall, Adam R.
• Gondara, Lovedeep
• Chan, Tracy
• Law, Jennifer H.
• Smith, Laurie W.
• Niekerk, Dirk J.
• Ogilvie, Gina S.
• Coldman, Andrew J.
• Warman, Rhian
• Reuter, Caroline
• Cuzick, Jack
• Lorincz, Attila T.

Titel

Evaluation of a validated methylation triage signature for human papillomavirus positive women in the HPV FOCAL cervical cancer screening trial

Ist Teil von

• International journal of cancer, 2019-05, Vol.144 (10), p.2587-2595

Ort / Verlag

Hoboken, USA: John Wiley & Sons, Inc

Erscheinungsjahr

2019

Quelle

Wiley Blackwell Single Titles

Beschreibungen/Notizen

• Human papillomavirus (HPV)‐based cervical cancer screening requires triage of HPV positive women to identify those at risk of cervical intraepithelial neoplasia grade 2 (CIN2) or worse. We conducted a blinded case–control study within the HPV FOCAL randomized cervical cancer screening trial of women aged 25–65 to examine whether baseline methylation testing using the S5 classifier provided triage performance similar to an algorithm relying on cytology and HPV genotyping. Groups were randomly selected from women with known HPV/cytology results and pathology outcomes. Group 1: 104 HPV positive (HPV+), abnormal cytology (54 CIN2/3; 50 <CIN2); Group 2: 103 HPV+, normal cytology with HPV persistence at 12 mo. (53 CIN2/3; 50 <CIN2); Group 3: 50 HPV+, normal cytology with HPV clearance at 12 mo. (assumed <CIN2), total n=257. For the combined groups, S5 risk score CIN2/3 relative sensitivity, specificity and positive predictive value (PPV) were compared with other triage approaches. Methylation showed a highly significant increasing trend with disease severity. For CIN3, S5 relative sensitivity and specificity were: 93.2% (95%CI: 81.4–98.0) and 41.8% (35.2–48.8), compared to 86.4% (75.0–95.7) and 49.8% (43.1–56.6) respectively for combined abnormal cytology/HPV16/18 positivity (differences not statistically significant at 5% level); adjusted PPVs were 18.2% (16.2–20.4) and 19.3% (16.6–22.2) respectively. S5 was also positive in baseline specimens from eight cancers detected during or after trial participation. The S5 methylation score had high sensitivity and PPV for CIN3, compatible with US and European thresholds for colposcopy referral. Methylation signatures can identify most HPV positive women at increased risk of cervical cancer from their baseline screening specimens. What's new? DNA methylation testing could simplify the triage process for screening HPV+ women for cervical cancer, according to new results from a case‐control study. Most pre‐cancerous cervical lesions do not progress to cancer, so triage is done to identify those lesions more likely to become cancerous and boost screening specificity. Here, the authors tested women in the HPV FOCAL study for baseline methylation using the S5 classifier. Methylation signatures, they found, performed with 93% sensitivity and 18% PPV for CIN3, comparable to the combination of cytology and HPV genotyping (86% sensitivity and 19% PPV).