Key Components of Cervical Cancer Screening
Updated: Sep 5, 2019
Cervical Cancer Screening & Treatment
What are the key components of a screening test for cervical cancer? How are these different in a resource-limited setting?
a. Resource-Rich Settings
Cervical cancer is the easiest cancer to prevent due to its long progression (10-15) years from atypical cells to fully fledged cancer. In a resource-rich setting, we typically see a three step process consisting of initial screening, colposcopy-guided biopsy, and treatment. This process assumes easy access to care - hospital, pathologist, or otherwise. There are various options for each step, each with their own positive and negative characteristics.
Regular screening is recommended by WHO at every 3 years with cytology (Pap smears) for women 21-65 years for women and another option of a combination of cytology and HPV DNA tests every 5 years for women 30-65 years of age. These screening methods enable early detection of cervical pre-cancers and early treatment before the cancer has metastasized. A Pap smear tests for presence of precancerous or cancerous cells on the surface of the cervix. It is named after George Papanicolau, a physician who discovered its usefulness in early detection of pre-cancer. It is conducted by a trained healthcare worker and involves using a modified spatula or cytobrush to obtain cell samples from the surface of the cervix.
It is important to note that only the top layer of cells in the cervix is accessed through these procedures. A cytology examination is then done on this sample, as will be discussed in greater detail below. Even though it has drastically decreased the incidence of cervical cancer, the Pap smear is overly sensitive and only about 0.1% of women with abnormal pap smears have high grade pre-cancer or cancer. Additionally, due to methods of sample collection abnormal cells could be missed. The HPV DNA test can identify the high risk HPV subtypes which cause cervical cancer. HPV testing alone does not replace the Pap smear but when used in combination with the Pap smear increases the sensitivity and specificity of screening. The HPV or cytology test is positive based of a classification known as the Bethesda system, the doctor recommends repeated HPV and cytology testing or colposcopy based off the degree of abnormality.
If a patient is referred to a colposcopy clinic they undergo for visual inspection with acetic acid (VIA) or visual inspection with Lugol’s Iodine (VILI) with image capture. During colposcopy, contrast agents; acetic acid for VIA or Lugol’s iodine for VILI are applied to the surface of the cervix. VIA causes aceto-whitening and mosaicism with a well defined margin for abnormal areas on the cervix due to increase in nuclei of epithelial cells, and no observed change for normal areas of the cervix. VILI causes a dark brown stain on normal areas of the cervix and a saffron yellow or mustard yellow stain on abnormal lesion areas. This is observed because iodine is glycophilic and normal cells store glycogen and hence up take the iodine. Abnormal cells have high metabolic rates, using up their glycogen and do not uptake the iodine.
If any suspicious pre-cancer areas are observed a biopsy is taken of the area and then sent to pathology which takes about 1 week. Pathology provided a diagnostic confirmation of whether the cervix is normal or precancerous. It also classifies the lesions as low grade (CIN1), highgrade (CIN2+) or cancer. If the pathology diagnosis is low grade the woman is requested to come back for a follow-up (since most CIN1 lesions regress on their own). If the pathology is high grade the patient returns for treatment at a laterdate.
If detected early, cervical cancer can be treated by removing the cancerous tissue in the cervix. The most common mode of treatment for cervical cancer in high-resource settings is the Loop Electrosurgical Excision Procedure(LEEP).This involves the use of a wire-loop with high current flowing through it to cut tissue. The LEEP can only be performed by a physician and requires a constant supply of power. The cut out tissue is sent to pathology to confirm that the entire lesion was removed.
b. Resource-Poor Settings
In regions where resources are limited, cervical cancer screening rates are often low. In many cases, women who are able to be screened are at risk being lost to follow-up. While the approach in high-resource hospitals is three-tiered, typically requiring at least three separate appointments, distance from a clinic, low capacity to serve the high volume of at-risk women, and other barriers to healthcare mean many women are unable to return for biopsy or treatment. This negates the effectiveness of the three-tiered approach use in resource-rich settings and leads to the need for the see-and-treat paradigm.
The See-and-Treat Paradigm
The screening process typically begins with visual inspection with Acetic Acid (VIA) or Lugol’s Iodine (VILI). Visual inspection can be digital, analog or just viewed with the naked eye, and is often conducted by community health workers Women who are suspected to have cancerous or pre-cancerous indications on their cervix are referred on the same day to a clinic for further testing. Where possible, the physician will conduct a colposcopy with the available medical devices and thereafter remove cancerous regions. This final step is often done through cryotherapy, a process during which a targeted pen is used to freeze specific parts of the cervix, resulting in their removal.
Although this process is low-cost, it tends to be subjective with high false positive and overtreatment rates. The low reproducibility and low specificity of the process requires additional quality control and training of clinicians. A cervical cancer screening device in a low-resource setting must be able to capture images of the cervix that can be analyzed immediately. The WHO recommends the see-and-treat approach for all lower and middle income countries with underdeveloped screening capabilities for cervical cancer, for reasons outlined below.
Access and Cost
In high-resource settings, there are few limits to the size, weight, and energy usage that colposcopes and other screening devices will require. However, these factors are critical in low- resource settings as devices may need to be transported between health clinics or across poor terrain to perform screenings in smaller communities. Similarly, lower cost devices will allow hospitals and health clinics to purchase these devices and increase their screening capacity.
Lack of pathologists and trained health professionals
In resource limited settings, we typically see a shortage of health practitioners with the training needed for the screening through treatment. For example, in Tanzania, there is 1 pathologist per 2.5 million people and the figures are very similar in Haiti. Furthermore, 60-75% of women are lost to follow up after cervical cancer screening. A low-resource device must address these issues in training and patients lost to follow-up, while maintaining low cost and high accessibility.
Integrated education and Quality Control
As mentioned above, the use of a qualitative visual assay like VIA for cervical cancer screening requires high training and quality control to ensure cancerous tissues are removed without over- treatment. Further, Pap smears and biopsies must be interpreted by a highly trained pathologist, for which there are typically very few in developing settings. Instead, devices in low-resource settings might incorporate computer algorithms to analyze cervix images or mobile health platforms to send images to experts in city centers or overseas. Also, because cervical cancer screening is not always performed by doctors and physicians, designing a simple tool with appropriate user interface will reduce training needed to operate thedevice.
Specific Needs for Low-Resource Settings
Accordingly, devices fit for resource-limited settings still need the high sensitivity and specificity of devices used for resource-rich settings, yet, must also be low-cost, easy-to-operate and can with stand rugged conditions including variable temperatures and voltages. In a number of these settings, practitioners cannot depend on their unreliable power sources to keep devices running so battery-operation may be a better alternative. Further, low-resource devices should have a high degree of portability for easy transport to other locations in times of need. As previously mentioned, clinicians may not have the proper skills or training in order to operate particular devices. With integration of device education and an easy-to-use design, it will be easier for ministries of health to train health practitioners and control the quality of healthcare delivery. Overall, a device for use in low-resource settings must fit the see-and-treat paradigm, increase accessibility, decrease cost, and integrate education and quality control while maintaining high sensitivity and specificity of a high-resource device.