ClickMedix founder partnered with University of Pennsylvania and Botswana-UPenn Partnership program to pioneer cervical cancer screening using mobile camera phones. *Note: This presentation contains medical images which may be unsuitable for those not accustomed.

1. Mobile T elemedicine
& E ducation:
Use of mobile telemedicine for cervical cancer
screening – improving access to cancer
prevention for HI V+ women in B otswana
T ing Shih
CEO & Founder
http:clickmedix.com

2. Mobile telemedicine is designed to simultaneously
solve these healthcare challenges
High costs Lack of
Inaccessible
Specialists
doctors •For providers: manage •Not enough
•No doctor nearby clinic operations for specialists to serve
•Long and rural areas patients
•For patients: travel •Specialists are often
inconvenient travel
•Long wait in line to costs, loss of wages, unavailable to rural
see doctors consultation population
payments, etc.
© ClickMedix, LLC 2012 http://clickmedix.com 2

3. HPV/HIV Co-Infection and Cervical Cancer
Prevention in Botswana
Slides adopted from:
Doreen Ramogola-Masire, MD
Country Director, Botswana-UPenn Partnership
University of Pennsylvania

4. Click to edit Master title style
Human papillomavirus (HPV)
• HPV is a relatively small virus containing circular double-
stranded DNA within a spherical shell (capsid)
• HPVs infect cutaneous epithelium (skin) and mucosal
epithelium (e.g. cervical and other anogenital mucosae)
55 nm
Slide courtesy of
Burd EM. Clin Microbiol Rev 2003; 16:1–17.
EXCCEL

5. Estimated numberedit Master title style (2002)
Click to of cases of cervical cancer
493,243 cases worldwide
North America Europe
14,670 59,931
Africa
78,897
South and Asia
Central America 265,884
71,862
< 9.2 < 16.1 < 26.2 < 32.6 < 87.3*
* per 100,000.
5 Ferlay J, et al. GLOBOCAN 2002 Cancer Incidence, Mortality and
Prevalence Worldwide. IARC CancerBase; Lyon, 2004.

6. Virtually all cervical cancers are caused
Click to editby HPV title style
Master
Global total HPV-attributable cancers in females, 2002
Attributable % all Attributable to
to HPV HPV HPV 16/18
cancer
Total in
Site % Cases % Cases
cancers females
Cervix 492,800 ~100 492,800 93.5 70+ 344,900
Vulva, vagina 40,000 40 16,000 3.0 80 12,800
Anus 15,900 90 14,300 2.7 92 13,100
Oropharynx 9,600 12 1,100 0.2 91 1,000
Mouth 98,400 3 2,900 0.6 97 2,800
Total 527,100 374,600
Slide courtesy of 6 Adapted from Parkin DM & Bray F. Vaccine 2006; 24(Suppl 3):S11–S25;
EXCCEL Walboomers JMM, et al. J P athol 1999; 18 9 : 12–19.

7. Click to edit Master title style
HPV lifecycle and immune evasion
Cervical HPV has many immune
canal evasion mechanisms:1
• Viral lifecycle occurs entirely
within epithelium
• No viraemia
Cervical
epithelium
• No cell death
• No inflammation
• Local immunosuppression caused
by viral proteins
• HPV ‘stealth’ and immune evasive mechanisms enable infection to persist1
• Persistent infection is a prerequisite2 but may not be enough alone –
co-factors may play an important role in progression to cervical cancer3,4
Slide courtesy of 1. Stanley M, et al. Vaccine 2006; 24S1:S1/16–S1/22; 2. Bosch FX, et al. J Clin Pathol 2002; 55:244–265;
EXCCEL
7
3. Ho GY, et al. N Engl J Med 1998; 338:423–428; 4. Richardson H. Cancer Epidemiol Biomarkers Prev 2003;
12:485–490.

8. Global prevalenceMaster title style
Click to edit of HIV Infection (2007)
Botswana

9. Botswana
Click to edit Master title style
HIV prevalence = 24.8% (ages 15–49)
 HIV modifies the natural history of HPV infection
 HIV-infected vs. non-HIV infected women more likely to
have:
 Persistent high-risk HPV infection
 Multiple HPV infections
 Precancer and ca cx earlier age/more rapid development
 High recurrence rates of treated lesions
 ART does not necessarily alter precancer/ca cx course
UNAIDS (2010) 'UNAIDS report on the global AIDS epidemic‘; http://www.unaids.org/globalreport/Global_report.htm

10. Use of mobile telemedicine for cervical
cancer screening
• Study: 99 women. VIA and HPV typing
• 71% HPV positive
• 26/93 VIA positive, also HPV +ve
• 92% of VIA +ve infected with at least one strain of high risk HPV
• HPV 35 - 13%
• HPV 16, 33, 53 - 9%
• HPV 52, 58 8%
K E Quinley et alJournal of Telemedicine and Telecare 2011; 17:
203–209.
© ClickMedix, LLC 2012 http://clickmedix.com 10

11. Linear Increase in Cervicaltitle style
Click to edit Master Cancer Cases
Botswana National Cancer Registry 1998-2008

12. Higher Clickof Cervical Cancertitle style
Risk to edit Master for HIV+ Patients
Botswana National Cancer Registry 1998-2008

13. Clinical Spectrum OfMaster title style
Click to edit HPV and Cervical Cancer
Peak Ages: 15-25 25-35 45-50
Schiffman et al., Lancet, 2007

14. Major steps in development
Click to edit Master title style
of cervical cancer
Infection with HPV
Persistent infection over 2-5yrs
may progress to pre-cancer
SCREEN AND TREAT
PRECANCER
Pre-cancer may
progress to invasive
cancer
Slide courtesy of Dr. Carla Chibwesha

15. Cervical cytology Master title style
Click to edit (Pap smear) screening
1. Woman aware of need for screening
2. Access to provider with supplies
3. Provider trained to take adequate specimen
4. Transport specimen to cytology lab
5. Cytology lab services
6. Report generated then sent to clinic
7. Clinic is able to report results to woman

16. Pap Smear to edit Master times-Botswana
Click Screening: Wait title style
1.
2.
Pap 3.
test + Colposcopy
& Return
Biopsy for
test - biopsy test + 4.
(confirm & results
diagnose) Treatment
test -
6 weeks 2-4 months 4-6 weeks 3-5 months
Loss to follow up Loss to follow up Loss to follow up Loss to follow up
TOTAL WAIT to complete treatment = 7 ½ to 12 MONTHS
Slide courtesy of Sara Forhan,,CDC

17. PEPFAR Funded Cervical Cancer Prevention Clinics
© ClickMedix, LLC 2012 http://clickmedix.com 17

18. Click to edit Master title style
Courtesy: Kelley Quinley

19. VisualClick to edit Master title style with
Inspection After Acetic Acid (VIA)
Enhanced Digital Imaging
Courtesy: Ann Steiner

20. Click to edit Master title style
VIA Strengths and Limitation
 Strengths:
 Very well accepted by health workers and women
 Simple; immediate result, very suitable for single-visit—”screen-
and-treat” (with cryotherapy) approach
 Requires only acetic acid, a speculum, and a light source (torch)
 Can be performed by nurses and midwives
 Single visit approaches using VIA once a lifetime cost less and
reduce CaCx by 26% compared with no screening
 Limitations:
 Sensitivity is not optimal, but is similar or better than Pap
Slide courtesy of Dr. Jose Jeronimo, PATH

21. Approach: create healthcare delivery channels
(mHealth platform) to connect patients to medical experts
Clinics
Hospitals
© ClickMedix, LLC 2012 http://clickmedix.com 21

22. Process Scenario: connects patients to medical
experts efficiently
$
Patient Medical experts
case
review and
collaborate on case
Patient sees Health provider 6.Links appropriate
local health (health workers, nurses,
health providers and From:
primary doctors)
provider with experts
uses ClickMedix Hospital Referral
health issue 7.Package data securely Centers
application to
capture with time series, multi-
appropriate media analysis
Medical Research &
patient info
Treatment Education Institutions
Treatment Treatment
and
Plan and training Advice and
follow-up
materials training tips
care
© ClickMedix, LLC 2012 http://clickmedix.com 22

23. Photographic Inspection withtitle style (PIA)
Click to edit Master Acetic Acid
 August 2009 in Gaborone, Botswana (18+ years old, HIV+, non-pregnant with no prior procedures)
 Speculum exam with an endocervical swab to obtain cells for HPV testing
 A nurse midwife used forceps to soak a cotton ball in 4% acetic acid applied to cervix and vaginal
fornices for three minutes. The cervix was then examined for acetowhite lesions using standard VIA.
 Images were transmitted by MMS and stored to be evaluated by the same nurse midwife who
performed the VIA examination 3months after initial visit, and blinded to her original evaluation.
 Subjects deemed VIA-positive were treated at the same visit with cryotherapy in the ‘see-and-treat’
model of care. In cases where the lesions occupied over 75% of the cervix, could not be fully
visualized, or were suggestive of invasive carcinoma, referral was made to a tertiary medical center
for treatment by loop electrosurgical excision procedure (LEEP) or cervical cone biopsy.
 HPV genotyping of ThinPrep endocervical samples was performed using Gold Taq to evaluate the
presence of 32 different genotypic HPV strains

24. Click to edit Master title style
Images from Camera Phone (5 megapixel with zoom)
Cervical photographs taken with the Samsung SGH-900 mobile
phone with zoom function and hand-held LED flashlight light
source.
A: Healthy cervix B: Cervix with acetowhite lesion
A B

25. Click to editResults title style
Master
VIA and detection of HPV:
92% of VIA-positive women were infected with at least one strain of high-risk
HPV
47% of subjects infected with high-risk HPV subtypes tested positive with VIA
PIA results:
Nurse VIA and PIA showed overall 81% diagnostic concordance (2 out of 4
nurses showed 100% concordance with women’s health expert
89% of negative expert PIA readings were determined to be negative by
nurse PIA
82% of positive expert PIA readings were determined to be positive by nurse
PIA
Nurses and experts agreed more often than expected by chance (P<0.001),
kappa statistic (0.7)

26. Digitally Enhanced Cervicography
• Useful Tool
o Allows provider assessment
o Patient education
o Remote consultation
o Record keeping
o Continuing education/feedback
o Global wireless communication
o Improves sensititivity and specificity of VIA
© ClickMedix, LLC 2012 http://clickmedix.com 26

27. Conclusion
 When photographs are taken with sufficient quality, mobile phone
technology can be an effective method of transmitting high-quality
images, allowing clinicians to make a diagnosis from a PIA photo
remotely that is similar to the diagnosis they would make with VIA in
person.
 Improvement for PIA picture quality: appropriate lighting, minimizing
glare from the metal speculum, and correctly placing the speculum for full
visualization of the cervix.
 Benefits of mobile-telemedicine: no need for constant electrical supply,
low cost, easy to use, minimal training, and allows for immediate image
transmission.
 Reduce prevalence of cervical cancer and associated morbidity and
mortality: opportunity for evaluation by a remote expert while the patient
is still in the clinic, easier to setup especially in areas where a high HIV
infection rate and limited access to gynecological services
© ClickMedix, LLC 2012 http://clickmedix.com 27

28. Future Applicability: Cancer in Women-Botswana
•1496 cases of ca cx reported during 10yr period
National Policy Doc for non-communicable disease 2010
© ClickMedix, LLC 2012 http://clickmedix.com 28

29. Product Suite: single platform to serve
multitude of healthcare and education needs
Solutions Description Customers
•Electronic health record (EHR)
• Primary care clinics, rural clinics
management
Click- • Home-visit health workers
•Tele-Primary Care
Health • Health Organizations
•Tele-Geriatric Care
• Patients
•Tele-Maternal & Pediatric Care
• Telehealth centers
•Tele-Dermatology
Click- • Secondary and tertiary hospitals
•Tele-Wound Care
Specialist • Primary Care Clinics, rural clinics
•Tele-Radiology
• Patients
•Medical student/resident
Click- • Medical Schools
training
Training • Training Institutions
•Remote health worker training
•Epidemiology research • Research Organizations
Click-Data
•Clinical trial research • Pharmaceutical companies
© ClickMedix, LLC 2012 http://clickmedix.com 29

30. Join us in creating the future of healthcare!
• Contact:
o Email: ting@clickmedix.com
o Phone: +1 202 618 0188
o Skype: ting.shih
• Visit: http://clickmedix.com
• Try: http://clickmedix.com/demo
© ClickMedix, LLC 2012 http://clickmedix.com 30