Slide 1: Multimodal Spectroscopic Imaging of the Cervix for Triaging Patients to Colposcopy
Multimodal Spectroscopic Imaging of the Cervix for Triaging Patients to Colposcopy L Twiggs, T De Santis, NM Chaktoura, D Ferris, L Flowers, M Lashgari, E Wilkinson, S Bambot, A Agrawal, and D Mongin EUROGIN 2003 LuViva Advanced Cervical Scan
Slide 2: Clinical Rationale
Clinical Rationale • Current triage methods miss disease and result in excessive false positive rate ALTS trial showed that current triage of colposcopy after referral for ASC-US/HPV+ and LSIL patients would still miss 30% to 40% of CIN3 disease Only about 5% of ASCUS Pap tests and 10% of LSIL Pap
Slide 3: Triage Background: ALTS Data Key Results
Triage Background: ALTS Data Key Results* • Adjunctive test would be useful because of the following findings: ASCUS/HPV+ would boost colposcopy referral rate to 56% ASCUS/HPV+ (26% CIN2/3) was nearly equivalent to LSIL (28% CIN2/3) Sensitivity of immediate colposcopy for CIN3 was 53.6% No u
Slide 4: Multimodal Spectroscopy Potential Benefits
Multimodal Spectroscopy Potential Benefits • Immediate result • Objective, more accurate test • Less discomfort • Time – Exam time: 3-5 minute test vs. 20-30 minute colposcopy – Patient time lost due to repeated office visits • Reduced cost to patient and healthcare system • Underserved populations
Slide 5: Multimodal Spectroscopy
Multimodal Spectroscopy Light In – Multiple wavelengths used Spectrometer to penetrate different tissue Results depths 1. Fluorescence Spectra - Reveal metabolic changes associated with neoplasia 2. Reflectance Spectra – Reveal structural changes associated with neoplasia Technology developed by Spe
Slide 6: Clinical Trial Objectives
Clinical Trial Objectives • Evaluate Multimodal Spectroscopy at four U.S. centers with diverse population – 414 subjects enrolled, 398 with evaluable cytology and histology – Age range 18-72, Median 27 • Primary goal: Develop and validate diagnostic algorithm for use in commercial system • Additiona
Slide 7: Study Hypotheses
Study Hypotheses • At equal sensitivity (90%), Multimodal Spectroscopy will produce a significant increase in specificity compared to the Pap test • At equal specificity (70%), Multimodal Spectroscopy will produce a significant increase in sensitivity compared to the Pap test • Additional analyses (
Slide 8: Patient Flow Chart
Patient Flow Chart Subject Had Referral Pap and was Scheduled for Colposcopy ASC-US Pap Dysplasia Pap Other Factors •Repeat ASC-US •ASC-H •Previous CIN •HPV Positive •LSIL •Recurrent Changes •W/Risk Factors •HSIL •Other Risk Factors CNDS Study 1) CNDS Spectroscopy 2) Sample taken for Pap and HPV 3)
Slide 9: Study Inclusion Criteria
Study Inclusion Criteria • Age 18 or above • Able to read or understand and give informed consent • Scheduled for colposcopy • Pap test within 120 days • Willing to undergo a Pap test and HPV test on day of study LuViva Advanced Cervical Scan
Slide 10: Study Exclusion Criteria
Study Exclusion Criteria • Pregnancy • Menstruating on the day of study • Radiation to genitourinary system within 1 year • Prior hysterectomy • Congenital anatomical cervical variant (e.g., double cervix) LuViva Advanced Cervical Scan
Slide 11: Cytology and Histology Results
Cytology and Histology Results HISTOLOGY CYTOLOGY Normal Benign CIN 1 CIN 2+ Total Within Normal Limits 62 19 13 11 105 Benign changes 17 10 6 3 36 ASCUS 41 27 19 15 102 LSIL 18 31 31 26 106 HSIL+ 3 3 6 37 49 Total 141 90 75 92 398 LuViva Advanced Cervical Scan
Slide 12: Smoothed ROC Curves for Training and Validation
Smoothed ROC Curves for Training and Validation Training (n=258) Validation (n=140) LuViva Advanced Cervical Scan
Slide 13: Comparative Diagnostic Performance
Comparative Diagnostic Performance: Combined Training and Validation Sets (at 90% Sensitivity for CIN2 Threshold) Modality Sensitivity Specificity NPV PPV Pap 90% 25% 89% 27% Alone Spectro- scopy alone 90% 41% 93% 32% Pap + Spectroscopy 90% 55% 95% 38% LuViva Advanced Cervical Scan
Slide 14: Cervical Maps of Patient with Dysplasia
Cervical Maps of Patient with Dysplasia CIN 1 CIN 2+ Biopsy sites marked with X’s LuViva Advanced Cervical Scan
Slide 15: Cervical Maps of Patient with Metaplasia
Cervical Maps of Patient with Metaplasia Metaplasia Biopsy sites marked with X’s LuViva Advanced Cervical Scan
Slide 16: PSA Test – Analogy to CNDS Results
PSA Test – Analogy to CNDS Results PSA Result Category Triage Percent Men (ng/mL) Recommendation with PCA 0-4 Normal Re-test in one year Less than 20% Ultrasound or 4 – 10 Borderline 20% to 30% biopsy Ultrasound guided > 10 High 40% to 60% or random biopsies Note: PSA result is used in combination w
Slide 17: Predictive Values of SpectRx Results
Predictive Values of SpectRx Results (Adds New Data and Processing; N =420) % % % % CNDS Risk Benign CIN1 CIN2 CIN3 Triage Strategy Result Level N=214 N=106 N=47 N=53 0-35 Low Risk 85% 12% 2% 1% Return to Screening N=141 36-50 Borderline Follow-up in 6 months 53% 30% 11% 6% N=122 Low or colposcopy 5
Slide 18: Study Conclusions
Study Conclusions • At 90% sensitivity, Multimodal Spectroscopy increased specificity of Pap test by 30% • Diagnostic algorithm trained on first 258 cases validated on the remaining 140 cases • There were no adverse events and patient acceptance of the procedure was excellent LuViva Advanced Cervica