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Published on: June 14, 2019
Informed cytology for triaging HPV-positive women: substudy nested in the NTCC randomized controlled trial
Christine Bergeron1, Paolo Giorgi-Rossi1, Frederic Cas1
1Department of Pathology, Laboratoire Cerba, Cergy Pontoise France (CB, FC); Servizio Interaziendale Epidemiologia, AUSL Reggio Emilia, Italy (PGR); Department of Pathology, S. Giovanni Hospital, Rome, Italy (MLS); Laboratory Department University Hospital "Città della Salute e della Scienza di Torino," Turin, Italy (BG); Department of Pathology, S. Chiara Hospital, Trento, Italy (PDP); Women's Health Department, University Hospital, Padua, Italy (DM); Veneto Oncology Institute IRCCS, Padua, Italy (MZ); Emilia-Romagna Region, Bologna, Italy (CN); Laboratory of Preventive Oncology, Institute for Cancer Study and Prevention (ISPO), Florence (MC); Department of Cancer Screening, Center for Epidemiology and Prevention in Oncology (CPO), University Hospital "Città della Salute e della Scienza di Torino," Turin, Italy (GR, NS, SR).
Informed cytology significantly improves human papillomavirus (HPV) testing triage accuracy for cervical cancer screening. HPV-positive women with informed cytology have higher sensitivity for detecting CIN2+, potentially allowing longer screening intervals.
Area of Science:
- Oncology
- Virology
- Gynecology
Background:
- Human papillomavirus (HPV) testing is crucial for cervical cancer screening but requires effective triage methods.
- Current randomized controlled trials (RCTs) often use cytology interpretation blinded to HPV status, limiting triage accuracy.
Purpose of the Study:
- To evaluate the diagnostic performance of HPV status-informed cytology compared to standard (blind) cytology in women undergoing cervical cancer screening.
- To assess the impact of informed cytology on the detection of cervical intraepithelial neoplasia (CIN2+).
Main Methods:
- A randomized controlled trial (NTCC RCT) involving women aged 25-60 years comparing HPV testing with cytology.
- Cytological slides from HPV-positive women were independently interpreted with awareness of HPV status.
- Sensitivity, specificity, PPV, and NPV for CIN2+ were calculated for HPV status-informed cytology.
Main Results:
- HPV status-informed cytology demonstrated a cross-sectional sensitivity of 85.6% for CIN2+ in HPV-positive women.
- Informed cytology showed a relative sensitivity of 1.58 for CIN2+ compared to blind cytology.
- Referral rates to colposcopy were similar between informed and blind cytology groups (0.95).
Conclusions:
- Cytology informed by HPV positivity offers superior sensitivity for detecting CIN2+ compared to blind cytology.
- This improved accuracy could enable extended screening intervals for HPV-positive, cytology-negative women, optimizing cervical cancer management.

