Innovative Approaches for
Global and Local
Cervical Cancer Prevention
Kathleen M. Schmeler, MD
Associate Professor
Department of Gynecologic Oncology
Inequity of Cervical Cancer
85% of cervical cancer cases occur in the developing world
Cervical Cancer
Worldwide:
• >500,000 new cases and >275,000 deaths annually
Developing Countries:
• 85% of cases and deaths occur in low and middle
income countries (LMICs)
• 1st or 2nd leading cause of cancer and related deaths
United States:
• 14th most frequent cancer among women
– 12,000 new cases and 4,000 related deaths per year
• Cervical cancer rates have decreased by ~70% over
the last 40y due to screening with Pap test
Siegel et al, CA Cancer J Clin, 2014
Globocan 2012 (WHO/IARC)
Cervical Cancer is Preventable
• Known Etiology:
– Human Papillomavirus (HPV)
• Prevention:
– HPV Vaccination
• Screening:
– Pap Test, HPV DNA Testing, VIA
• Treatable Pre-Invasive Phase:
– Cervical Cone/LEEP/Cryotherapy
– Takes years to progress from CIN
to cancer
Dr. Harald zur Hausen
Nobel Prize, 2008
Why We Still Need Screening
• Poor vaccination rates
• Existing vaccines do not
cover all high-risk HPV types
• Vaccines do not treat preexisting HPV infections
– 2 generations of women
*Screening will be necessary for
the foreseeable future and still
recommended after vaccination
Dr. George Papanikolaou
1883 - 1962
Cervical Cancer Prevention in USA
Three Clinical Visits:
1. Pap test +/- HPV testing
2. Colposcopy with cervical biopsies if
abnormal Pap
3. If significant precancerous lesions (<5%) conization/LEEP/cryotherapy
– Removal or ablation of precancerous lesion
** Not feasible in low resource settings
Availability of Pathologist
Number of People per
Pathologist:
• UK: 15,108*
• US: 19,232**
*Royal College of Pathologists, 2012
**Anatomic and Clinical Pathologists,
AAMC, 2007
Adesina et al., Lancet Oncology, 2012
Visual Inspection with Acetic
Acid (VIA) and Cryotherapy
• Low cost
• Requires 1 visit “See & Treat”
• India study:
• >150,000 women
• VIA by Primary Health Workers
PWH vs. cancer education every
24 months x 4 rounds
• 31% decrease in cervical cancer
mortality
Shastri et al, ASCO Proceedings, 2013
HPV Testing in Low-Resource Settings
India:
• Randomized >131,000 women ages 30-59
to a single lifetime screening test:
– Pap, VIA, HPV testing, or standard treatment
(cervical cancer education)
• A single HPV test led to a 50% decrease
in cervical cancer incidence and mortality
Sankaranarayanan et al, NEJM, 2009
Limitations of HPV Testing
• Cost: US$50-100
• Need laboratory
• Waiting time of several days/weeks for
results
• Several low-cost, rapid tests under
development:
– careHPV® (Qiagen)
– GeneXpert® (Cepheid)
Screening in Low-Resource Settings
Both VIA and HPV testing have low specificity:
• Many “false positive” results
• Overtreatment
• Increased costs
• Unnecessary concern for patients
• Limited availability of colposcopists and
pathologists in low-resource settings
** Need better methods to identify patients
needing cryotherapy or other intervention
High-Resolution Microendoscope
(HRME)
• Novel cervical visualization technique
• Developed by Dr. Rebecca Richards-Kortum
and team at Rice University
• Assesses pathologic features in vivo in realtime vs. performing colposcopy and biopsy
No colposcopist, lab, or pathologist needed….
High-Resolution Microendoscope (HRME)
• Proflavine (topical contrast agent that stains
nuclei) is placed on cervix
• A fiber-optic probe is placed on the cervix
• Fluorescence from the proflavine-stained
epithelium is transmitted back to the HRME
unit
• Image is displayed on a computer screen in
real-time
High-Resolution Microendoscope (HRME)
HRME
• Image analysis software quantifies
features of typically evaluated by a
pathologist on a biopsy:
– Nuclear size
– Calculates nuclear/cytoplasmic (N/C) ratio
– Nuclear crowding
– Nuclear pleomorphism
• Assessment is in vivo and in real-time
Normal vs. HG Dysplasia (CIN2/3)
Mobile HRME (mHRME)
Cell Phone Based System
Pilot Study - China
• 174 women in rural China
• HPV testing, VIA, colposcopy, and HRME imaging
• 69 women had abnormalities on colposcopy:
– Only 12 (17%) showed CIN2+ on biopsy
• HRME imaging:
– correctly classified all 12 CIN2+ (100%) as
abnormal
– correctly classified 38 of the remaining 57 (67%)
as normal
– Correctly classified 100% of HPV+ pts with CIN2+
Pierce et al, AACR Cancer Prev Res, 2013
Pilot Study – Barretos, Brazil
Collaborative Effort:
• José Humberto Fregnani (Barretos Cancer
Hospital)
• Rebecca Richards Kortum (Rice
University)
• Kathleen Schmeler (MD Anderson)
Pilot Study – Barretos, Brazil
Objectives:
1. Determine the feasibility of using HRME
in Brazil
2. Test the performance of HRME compared
with VIA and standard colposcopy with
cervical biopsies
Pilot Study – Barretos, Brazil
Preliminary Results:
• Enrollment complete (n=59 patients with
abnormal screening Pap tests)
• 46 patients had abnormal findings on VIA
and/or colposcopy with 79 biopsies
performed
• Central pathology review and image
analysis is currently underway
LIMAC Study
Low-cost Imaging with Microendoscopy
for Cervical Cancer Prevention
• Brazil (Barretos and rural areas using
mobile units)
• El Salvador
• Texas/Mexico border??
* Supported by the MD Anderson Sister Institution
Network Funds and the NCI Center for Global Health
Vaccinate Your Kids Against HPV!