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Using Mobile Phones for Cervical Cancer Screening
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Using Mobile Phones for Cervical Cancer Screening

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ClickMedix founder partnered with University of Pennsylvania and Botswana-UPenn Partnership program to pioneer cervical cancer screening using mobile camera phones. ...

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.

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  • Human papillomavirus
  • Estimated number of cases of cervical cancer (2002) The global distribution of cervical cancer cases per 100,000 individuals is shown, based on GLOBOCAN data from 2002. Reference Ferlay J, et al. GLOBOCAN 2002 Cancer Incidence, Mortality and Prevalence Worldwide. IARC CancerBase; Lyon, 2004 .
  • Virtually all cervical cancers are caused by HPV 99.7% of cervical cancer cases are attributable to HPV. Cervical cancer accounts for 93.5% of all HPV-related cancer globally, and over 70% of this type of cancer is caused by HPV 16 and 18. Vulval, vaginal, anal, oropharyngeal and mouth cancers combined account for 6.5% of all HPV cancer. Note that for cancers of the vulva, vagina, anus, oropharynx and mouth, a greater range in the percentage of cases attributable to HPV has been reported elsewhere. Munoz and colleagues (2006) reported that approximately 60–90% of vulval and vaginal cancers, 88–94% of anal cancers, 36% of oropharyngeal cancers (range 11–100%) and 24% of mouth cancers (range 4–80%) are HPV positive. References Parkin DM & Bray F. Vaccine 2006; 24 (Suppl 3) : S11. Mu ñ oz N, et al. Vaccine 2006; 24 (Suppl 3) : S1. Walboomers JMM, et al. J Pathol 1999; 189: 12–19.
  • The virus is thought to infect the basal cell layer of the epithelium via microabrasions. It then uses the host cell machinery to replicate viral DNA and express virally encoded proteins. Finally, new virus particles are assembled in the upper layers of the epithelium and virus is released with the cells as they are shed from the epithelial surface. HPV lifecycle and immune evasion HPV has several mechanisms for avoiding the immune system. HPV infects and multiplies in basal cells of the epithelial layer, which have a naturally short lifespan. HPV does not replicate in the blood (no viraemia) and the infection is not spread systemically. As a result, HPV does not need to destroy the host cell and, in the absence of cell death or a danger signal, HPV fails to trigger inflammation and an immune response. In addition, HPV downregulates the expression of interferon genes. Type 1 interferons are cytokines that have antiviral and antiproliferative properties, and HPV oncoproteins E6 and E7 can directly inhibit these antiviral pathways in the cell. Reference Stanley M. Vaccine 2006; 24: S16–22.
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  • 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 nmSlide 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 worldwideNorth 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 MasterGlobal 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 cancer3,4Slide 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 CancerPeak 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) screening1. Woman aware of need for screening2. Access to provider with supplies3. Provider trained to take adequate specimen4. Transport specimen to cytology lab5. Cytology lab services6. Report generated then sent to clinic7. Clinic is able to report results to woman
  • 16. Pap Smear to edit Master times-Botswana Click Screening: Wait title style1. 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 styleImages from Camera Phone (5 megapixel with zoom)Cervical photographs taken with the Samsung SGH-900 mobilephone with zoom function and hand-held LED flashlight lightsource.A: Healthy cervix B: Cervix with acetowhite lesion A B
  • 25. Click to editResults title style MasterVIA and detection of HPV:92% of VIA-positive women were infected with at least one strain of high-riskHPV47% of subjects infected with high-risk HPV subtypes tested positive with VIAPIA results:Nurse VIA and PIA showed overall 81% diagnostic concordance (2 out of 4nurses showed 100% concordance with women’s health expert89% of negative expert PIA readings were determined to be negative bynurse PIA82% of positive expert PIA readings were determined to be positive by nursePIA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