Low-cost screening options for cervical cancer: Dr. Gauravi Mishra & Dr. Sharmila Pimple
M3 India Newsdesk Nov 28, 2018
Dr. Gauravi Mishra and Dr. Sharmila Pimple, experts in Preventive Oncology list the various low-cost screening tests available for detection of cervical cancer, one of the largest contributors to the cancer burden in India.
Cervical cancer is the fourth most common cancer afflicting women worldwide, and a leading cause of cancer mortality in low- and middle-income countries. As per WHO reports, these regions account for approximately 90% of deaths from cervical cancer and hence comprehensive management of this debilitating disease is the need of the hour.
In low-income countries, like India, women, especially those living in rural regions, have limited accessibility to screening procedures and treatment facilities. This coincides with the fact that more than 70% of cervix cancer patients in India present at stages III and IV and hence represents a dismal survival rate.
On the other hand, advanced healthcare scenarios in high-income countries (HICs) have led to a reduction in the incidence of and deaths from cervical cancer. Regular screening has lead to prompt diagnosis and early treatment, which in turn halts disease progression.
An approach that encompasses effective screening and treatment programmes, early diagnosis, and efficient preventive strategies, can help reduce the global burden of this disease in low- and middle-income countries.
Screening/diagnostic tests to detect cervical precancers and cancers
Different screening tests are now available to detect precancerous lesions and cancers, and each test has its own pros and cons. Selection of the most suitable test depends largely on the settings in which it is to be used.
The international standard of cervical cancer screening is cytology or the PAP smear. Another option is the HPV test, which involves testing the DNA of the human papillomavirus (HPV), which is closely associated with the development of cervical cancer. The HPV test costs substantially more than cytology and is routinely used in HICs.
Cytology-based screening - the gold standard for cervical cancer screening?
Cervical cytology or PAP smear has been the mainstay of detecting cervical cancer. Screening programs based on cytology have demonstrated a dramatic decline in the incidence and mortality from cervical cancer.
Even though cytologic screening can be regarded as the archetype of screening tests, there are some inherent limitations associated with it. Sensitivity problems, failure to acquire adequate specimens, interobserver bias, and misinterpretations are some other problems which hinder effective implementation. Robust infrastructure and rigid quality assurance procedures can help to maintain cytology-based screening programs.
Cytology-based screening test can be further classified as follows:
- Conventional cytology: The conventional method comprises a microscopic examination of cells from the ectocervix and endocervix, by specially trained technologists and doctors. Even though the conventional method boosts of a high specificity, high false negative rate and low sensitivity for the detection of CIN 2+ are some major limitations. All these dictate frequent repetition of the test to achieve programmatic effectiveness.
- Liquid-based cytology: Liquid Based Cytology (LBC) has largely replaced conventional cytology due to its practical advantages. The method guarantees transfer of homogeneous cells to the slide, thus facilitating improved detection of intraepithelial cervical neoplasia and preinvasive and invasive glandular lesions. This point makes liquid-based cytology a preferred method, even though it is associated with a high cost and high infrastructural requirements.
Automated analysis of PAP smears
The automated version of PAP testing uses computerised analysis to evaluate PAP smear slides. The system is based on the concept that malignant cells can be differentiated on the basis of nuclear size and optical density.
The AutoPap System
The AutoPap System utilises two slide classification algorithms to identify abnormal PAP smears. In the initial screening window, the system identifies 25% of slides as normal and confers the rest as having high probability of abnormal cells, which are then screened by cytotechnologists.
AutoCyte Screen
AutoCyte Screen works on the same principle of algorithmic classifiers as does the AutoPap. The method involves the presentation of various cell images to a human reviewer, after which the device reveals its determination based on a ranking as to whether a manual review is warranted.
A diagnosis of “within normal limits” is given when the findings of both the reviewer and the computer match and no further review is needed. The cases which are identified as abnormal by the cytologist or the computer ranking are subjected to manual review.
Visual examination of cervix – Enabling the “screen and treat” strategy!
Despite its limited specificity, visual inspection of the cervix has reemerged as a screening tool for low-resource settings. Visual inspection can have great impact in developing countries like India. Studies have shown that utilising screening strategy involving visual inspection after application of acetic acid (VIA) can reduce the lifetime risk of cervical cancer mortality by approximately 25 to 36%.
The reasons for increased use of visual approach are its low cost and ability to provide immediate results. Thus visual methods allow the implementation of “screen and treat” strategy. These methods are best screening option for women who do not have access to cervical cytology and human papillomavirus (HPV) testing.
Four different types of visual examination methods are currently available:
- Unaided visual inspection or downstaging: This method involves examination of the cervix with the naked eye without the use of acetic acid. Even though it has been suggested as an alternative method for cervical cancer screening in developing countries, it has demonstrated poor outcomes.
- Cervicoscopy (VIA or visual inspection after application of acetic acid): Cervicoscopy or direct visual inspection is the termed used to denote visual inspection of the cervix, with naked eye, after the application of 3 to 5% acetic acid. VIA offers a satisfactory method to detect cervical neoplasia.
- The acetic acid causes coagulation of cervical areas depicting dysplasia or invasive cancer
- The areas depicting such cells appear acetowhite and hence are able to differentiate from the normal cells
- Gynoscopy (aided visual inspection): Gynoscopy involves VIA performed under low magnification. As per the Mumbai cervix cancer trial, gynoscopy has similar sensitivity and specificity as compared with VIA and does not have any added benefit over VIA.
- Schiller's test (visual inspection after application of Lugol's iodine): Schiller's test involves the visual examination of cervix after the application of Lugol's iodine. The test utilises the fact that precancerous cells and invasive cancer lack glycogen whereas, squamous epithelium contains glycogen. When in contact with Lugol's iodine,
- normal mature squamous epithelium appears black
- precancerous lesions and invasive cancer due to the absence of glycogen, turn mustard or saffron yellow
Further testing to confirm the result and determine the severity of the abnormality
- Colposcopy: Positive screening tests during cytology tests or visual inspections warrant referral for colposcopy. Colposcopy involves magnified visual examination of the uterine cervix to identify the biopsy site for secondary histological diagnosis. If the squamocolumnar junction cannot be visualised in a colposcopy, endocervical curettage is usually obtained.
- Cervicography: It involves distant evaluations of photographic images of the cervix. It may be regarded as an adjunct method of cervical cancer screening. The images or cervicograms are classified as negative, atypical, or positive by certified evaluators. Cervicography cannot be recommended for universal screening, although it may help in the follow-up of patients with a mildly abnormal cervical smear.
- Human papillomavirus DNA test: The role of human papillomavirus in cervical cancer and its immediate precancerous lesions has been well established. A number of laboratory-based approaches for detecting HPV in cervical samples are currently available.
The FDA approved Hybrid Capture II kit is a commonly used test and can detect 13 high-risk HPV viral types (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68). It is especially useful to evaluate women, above 30-35 years of age, with equivocal PAP test.
As per a cluster randomised controlled trial in rural India HPV testing is the most objective and reproducible of all cervical screening tests. It also requires less training and quality assurance procedures for its conduction. The cost associated with HPV testing makes it currently unaffordable to be used as a population-based screening tool in India.
Based on: Mishra GA, Pimple SA, Shastri SS. Prevention of Cervix Cancer in India.Oncology.
Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.
-
Exclusive Write-ups & Webinars by KOLs
-
Daily Quiz by specialty -
Paid Market Research Surveys -
Case discussions, News & Journals' summaries
