<![CDATA[Treatment of precancer lesions: overcoming the bottleneck]]>

Background
Cervical cancer is the first or second most common cancer and a leading cause of cancer deaths among women in low-and middle-income countries (LMICs) where nearly 90% of the deaths occur. The primary reason for this inequitable burden of disease is the absence of routine screening services in most LMICs. In 2012, Malawi was estimated to have the highest rate of cervical cancer in the world with an age-standardized rate of 75.9 per 100,000 women¹. In 2014, only 22% of Malawian women had access to cervical cancer screening using visual inspection with acetic acid (VIA). While many LMICs have started pilot screening programs in recent years, only a few programs have expanded to reach more than a small proportion of the women who need them.

Even when screening services are available, women identified as positive on screening tests often have little or no access to effective precancer treatment. In Malawi, 60% of precancerous lesions in 2014 were not trewated due to the unavailability of standard treatment (cryotherapy using carbon dioxide or nitrous oxide gas). Factors constraining treatment availability include the initial cost of equipment, the cost of ancillary supplies, and the burden of initial training and maintenance of skills when treatment is needed for only a fraction of women screened. While cryotherapy was seen as holding great promise, it has proven to be unsustainable due to the high cost and limited supplies of gas and the difficulty in central procurement and distribution of gas cylinders. In Malawi, in 2014, a cryotherapy unit cost US$1,350, and a cylinder of nitrous oxide gas cost $930, which provides 20 treatments on average ($46.50 per treatment in a country with a health expenditure of $14.50 per capita in 2010).

New technology options
Two non-gas-based treatment technologies have been identified. The CryoPen® Surgical System (CryoPen, Inc., Texas, USA) uses the same ablative principle of freezing abnormal tissue, but creates freezing temperatures using a recirculated refrigerant gas system powered by electricity. The device has been available in the United States for several years, but the company recently modified the design to make it more robust, easier to transport, and affordable for LMICs. An alternative ablative approach previously known as cold coagulation (also called thermal coagulation because it uses heat rather than cold) uses a metallic probe at 100 to 120 degrees centigrade for 30 to 60 seconds to destroy precancerous lesions. One version of the coagulator with probes (WISAP Medical Technology GmbH, Germany) requires electricity and costs about $3,400 (2013 discount by WISAP for Malawi). Another version being developed by a United States company (Liger Medical, LLC, Utah, USA) is a patent-pending hand-held battery-powered device that is anticipated to sell for about $1,000. Development of the Liger Medical unit is expected to be completed in 2016. Thermal coagulation is shown to be safe, effective, and suitable for low- to mid-level health providers in LMICs.2,3 With the availability of these new treatment options, both static and outreach services can be carried out more readily.

Experience with alternative treatment approaches
Experience with CryoPen in low-resource settings is limited, although a few small exercises were conducted in countries in Africa and Latin America.
A field evaluation is planned for Uganda in 2016. The bulk of the experience with thermal coagulation comes from the United Kingdom and a few scattered individual users in Africa and Asia. The most extensive experience comes from Nkhoma Hospital in rural Central Malawi, where a cervical cancer program in partnership with the Scottish Government, the University of Edinburgh, and NHSScotland turned to thermal coagulation in response to challenges with conventional cryotherapy. Nkhoma Hospital screened 7,088 women from October 2013 through March 2015, with 429 (6.1%) VIA positive, of whom 361 (84.1%) had same-day treatment with thermal coagulation. Of those treated, 234 (62.4%) returned for a 6-month follow-up, and of these, 220 (94%) were healed with no evidence of persistent lesions4. The procedure was well tolerated with minimal complaints of discomfort and few return visits for complications.

Next steps
To ensure wide availability of treatment options in LMICs, several parallel activities are needed. The development of technologies like CryoPen and the Liger Medical thermal coagulation unit must be completed and the units validated. A more diverse evidence base on efficacy is needed, particularly for thermal coagulation since there has been less experience with it. Nkhoma Hospital is currently working with the Malawi National Cervical Cancer Program to provide data on safety and effectiveness of thermal coagulation, but data from other sites would also be needed. Training programs will require materials for new treatment methods. Nkhoma Hospital has developed a training manual for thermal coagulation users that can serve as a starting point. Since many countries rely on World Health Organization (WHO) guidelines, it will be important to present essential information on equipment specifications and clinical performance to WHO for official endorsement. Only by overcoming the current bottlenecks to precancer treatment can we ensure that screening programs achieve their intended purpose and reduce the burden of this disease.

References

1. Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available at: http://globocan.iarc.fr. Accessed February 25, 2016.
2. Treatment Technologies for Precancerous Cervical Lesions in Low-Resource Settings: Review and Evaluation. Seattle: PATH, 2013. Available at: www.rho.org/files/rb5/Treatment_technologies_%20precancerous_cx_lesions_PATH_2013.pdf. Accessed February 29, 2016.
3. Dolman L, Sauvaget C, Muwonge R, Sankaranarayanan R. Meta-analysis of the efficacy of cold coagulation as a treatment method for cervical intraepithelial neoplasia: A systematic review. BJOG. 2014; 121:929–942.
4. Campbell C, Kafwafwa S, Brown H, et al. Use of thermo-coagulation as an alternative treatment modality in a ‘screen and treat’ programme of cervical screening in rural Malawi. Int J Cancer. In press.

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Dr. David Morton, PhD
Deputy Medical Director Consultant Physician, P.O. Box 48, Nkhoma, Malawi
kuluva2@gmail.com

Dr. Vivien Tsu, PhD, MPH
Associate Director Reproductive Health PATH, Seattle, USA
vtsu@path.org

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