Slide 1: Comparison of HPV Testing and Spectroscopy Combined with Cytology for Detection of High-grade Cervical Neoplasia
Comparison of HPV Testing and Spectroscopy Combined with Cytology for the Detection of High- grade Cervical Neoplasia C Werner, W Griffith III, R Ashfaq, D Gossett, E Wilkinson, S Raab, S Bambot, D Mongin, M Faupel ASCCP Biennial 2006 LuViva Advanced Cervical Scan
Slide 2: Current screening and diagnostic strategies have reduced cervical cancer, however...
Current screening and diagnostic strategies have greatly reduced the incidence of cervical cancer, however…. • Significant CIN2+ disease goes undetected (cytology & colposcopy) • Current management algorithms are multi- stepped and varied combinations of cytology, HPV DNA testing, and colposcopy • Y
Slide 3: HPV DNA Testing
HPV DNA Testing • Currently used for: – Primary screening age > 30 – Triage of ASC-US, some LSIL cytologies – Post-colposcopy surveillance (histology negative or LSIL) – Post-treatment surveillance • High sensitivity for CIN2+ (> 90%) • Low specificity due to high prevalence in general population (e
Slide 4: Clinical Trial Objective
Clinical Trial Objective • Compare performance of cervical spectroscopy (CS) with HPV DNA testing (HPV) when used in conjunction with cytology in detecting CIN2+ • Hypothesis: CS is as sensitive as HPV but more specific LuViva Advanced Cervical Scan
Slide 5: Rationale
Rationale • HPV DNA testing detects HPV infection • CS detects the metabolic and morphologic changes occurring in neoplastic tissue LuViva Advanced Cervical Scan
Slide 6: Cervical Spectroscopy Device
Cervical Spectroscopy Device • Rated as nonsignificant risk device: FDA •Base unit and hand-held unit •Contact tube 1” diameter •Exam time: 3 to 4 minute test LuViva Advanced Cervical Scan
Slide 7: Multimodal Spectroscopy
Multimodal Spectroscopy Light In – Spectrometer •Multiple wavelengths of UV and visible light used to penetrate different tissue Results depths •Multiple, non-overlapping, equally distributed points 1. Fluorescence Spectra - Function of metabolic changes 2. Reflectance Spectra – Structural changes a
Slide 8: Methodology
Methodology • Prospective double-masked trial – Clinicians masked to spectral output – Technical team masked to clinical results (history, colposcopy, cytology, histology, HPV test) • Approved by IRB at University of Texas Southwestern Medical Center at Dallas • Conducted in a gynecology clinic of P
Slide 9: Methodology
Methodology • All colposcopies performed by one of 2 experienced colposcopists • Pathology QA: agreement by 2 of 3 pathologists (1 site / 2 outside pathologists) • Study was funded by a grant from NCI and by Guided Therapeutics (sponsor) LuViva Advanced Cervical Scan
Slide 10: Study Inclusion/Exclusion Criteria
Study Inclusion/ Exclusion Criteria • Age 18 or above • Scheduled for colposcopy • Able to give informed consent • Cervix present and cytology within 120 days • Not pregnant • Not menstruating LuViva Advanced Cervical Scan
Slide 11: Subjects Referred for Colposcopy
Subjects Referred for Colposcopy ASC-US (56) Other (4) •Repeat ASC-US •LSIL (35) •Recurrent Changes •HPV Positive •ASC-H/ HSIL (7) •Previous CIN •W/Risk Factors •Other Risk Factors CS Study 1) Spectroscopy 2) Pap and HPV test 3) Colposcopy 4) Biopsy (if indicated) LuViva Advanced Cervical Scan
Slide 12: CS Spectral Output + Concurrent Cytology Algorithm
CS Spectral Output + Concurrent Cytology Algorithm •Data from previous studies •Numeric index that correlates with likelihood of CIN2+ Squamous Normal = Blue Transition Zone = Green High Grade Dysplasia = Red LuViva Advanced Cervical Scan
Slide 13: Results
Results • 109 were enrolled and completed the study • CS data from 5 (4.6%) cases not evaluable due to device malfunction or operator error • 104 subjects included in final data analysis LuViva Advanced Cervical Scan
Slide 14: Results
Results • Racial diversity – 57% African/ American – 31% Hispanic – 11% Caucasian – 1% Asian/ American • Median age 31 (range 16-57) • No cases of invasive cancer LuViva Advanced Cervical Scan
Slide 15: Performance Comparison
Performance Comparison • Sensitivity of Pap+HPV and Pap+CS were identical – CIN2/ CIN3 95% (19/20) – CIN3 100% (10/10) – Single case missed was borderline CIN1/CIN2 lesion • Specificity – Pap+ HPV 27.4% (23/84) p <0.0001 – Pap+CS 65.5% (55/84) McNemar’s test LuViva Advanced Cervical Scan
Slide 16: Study Conclusions
Study Conclusions • Pap+CS demonstrated high sensitivity (95%) and specificity (65%) for detection of CIN 2/ CIN 3 in a population women at high risk for cervical disease • Specificity was significantly higher than Pap+HPV, which could potentially reduce the number of colposcopy referrals in patient
Slide 17: Limitations
Limitations • Small sample size – Limits subgroup analyses • Inclusion of ASC-H, LSIL, HSIL referral Paps did not mirror current management algorithms exactly LuViva Advanced Cervical Scan
Slide 18: Future Potential
Future Potential • Alternative triage and surveillance strategy in the management of minor cytological and histological abnormalities • Localize high grade neoplasia for directing biopsy and /or treatment • Stand-alone primary screening technology for detection of CIN2+ LuViva Advanced Cervical Scan