VISUAL INSPECTION WITH ACETIC ACID FOR CERVICAL CANCER SCREENING- AN EFFECTIVE STRATEGY IN LOW-RESOURCE SETTINGS

ABOUT AUTHORS:
Dr. Balram Soni*
M.Pharm., Ph.D.
Psychiatric Centre, S.M.S. Medical College Jaipur, Rajasthan
brpharma@rediffmail.com

ABSTRACT:
A simple screening technique using an inexpensive agent dramatically reduced deaths related to cervical cancer in a population of Indian women. Visual inspection with acetic acid or vinegar (VIA), conducted by non medical personnel trained to deliver basic healthcare, cut the death rate by 31%. This strategy is effective and can be implemented on a broad scale in low-income countries. "There was almost no over diagnosis, it doesn't require a laboratory, and it can be widely implemented in the lowest-resource settings, such as India," If implemented nationally in India, it could prevent 22,000 cervical cancer deaths. If taken globally to the lowest-resource countries, it could prevent around 72,000 deaths in the developing world.

REFERENCE ID: PHARMATUTOR-ART-1927

INTRODUCTION:
Cervical cancer is the leading cause of cancer-related mortality in women in many developing nations, where access to Pap test screening is very limited or nonexistent. Widespread Pap test screening in high-income countries has significantly reduced the incidence and subsequent death rate from cervical cancer by 80%.

"There is no cervical cancer screening program in India because it is not feasible," There is inadequate infrastructure, a lack of trained human resources, logistic difficulties, and a relatively high cost.

Therefore, the researchers looked at VIA, which is a simple visual test that can be done without laboratory support. "It consists of an application of 4% vinegar to the cervix, and the results are available in 1 minute.

A swab of vinegar and a lamp is all that’s needed to perform cervical cancer screening, according to a 15-year study in India that found the low-cost alternative to Pap smears can save lives.

The vinegar-based screening approach lowered cervical cancer death rates among Indian women by 30 percent, researchers found. The study presented at the American Society of Clinical Oncology’s annual meeting in Chicago included 150,000 women.

While the Pap smear has reduced deaths from cervical cancer by 80 percent in the U.S. and other developed nations, the disease is the second most-common malignancy in less-developed regions in the world after breast cancer, according to the World Health Organization. Screening with vinegar doesn’t require specialized laboratory equipment, making it cheaper and more accessible in places where health-care infrastructure is poor.

Study Findings
Half of the women in the study received the vinegar screening, and half got no screening, which is the current standard of care in India, the authors said. The incidence of cancer was similar between the two groups, with about 27 cancers for every 100,000 women in the screening group and 28 cancers for every 100,000 in the non-screening group. That meant that the screening didn’t lead to over-diagnosis, researchers said.

Pap smears work by scraping skin off the cervix and examining it with a microscope, or doing a DNA test. With vinegar, the test is done by applying it to a cotton swab and brushing it onto the cervix. After 60 seconds, normal tissue stays the same color, and cancerous tissue turns white. This can be seen using a lamp. Because the results are known immediately, this also provides an advantage to rural women who may have to travel to seek further care.

Death Rates
About 11 percent of patients in the vinegar screening group died from cervical cancer during the trial, compared with 16 percent who weren’t screened, according to the study.

When the study began in 1996, the Indian Council of Medical Research found it wouldn’t be feasible to screen a quarter of the population even if the existing Pap facilities were multiplied 12-fold. The study, by researchers from Tata Memorial Center in Mumbai, was supported in part by the U.S. National Institutes of Health.

The vinegar strategy may aid many low-income women. The screenings can be done by primary care workers, which further lowers the cost. Last year, the Geneva-based WHO reported that vinegar screenings had been successfully implemented in six African countries, and made recommendations for more widespread use of the practice, saying it’s safe and simple for women in poor nations¹.

BACKGROUND:
Cervical cancer, the second most commonly diagnosed cancer among women worldwide, can be a preventable disease. Although the Pap smear remains the most common screening test for cervical cancer, many less developed countries do not have adequate resources to implement cytology-based prevention programs. An alternative, low-cost test, visual inspection using acetic acid (VIA), has emerged for use in low-resource settings where it can be performed by auxiliary health professionals^2-4. VIA is similar to colposcopy in that acetic acid is applied and any acetowhite lesion is visualized, although with VIA there is no magnification.

VIA accuracy studies have yielded a range of sensitivity and specificity values spanning from approximately 60 percent to over 90 percent ^5-15. While this range is narrower than observed for other tests including cytology (23% to 99% for sensitivity and 7% to 97% for specificity), it is important to investigate possible reasons for inter-study variability. The VIA studies cited above have involved a variety of reference standard measures. These include: 100 percent biopsy sampling, a combined colposcopy/biopsy reference standard for all participants, biopsy for colposcopically-suspicious lesions only, and colposcopy with histology only for women test-positive on all screening tests [i.e., visual inspection, Pap, human papillomavirus (HPV) and cervicography. Even among studies with similar reference standard measures, another source of variability across studies could be differences in the quality of the reference standard. Subjective (human) error may have affected the quality of colposcopy or the quality of tissue collection, slide fixing and biopsy interpretation which could have led to misclassification of the reference standard ^16,17.

Most published studies on VIA involve use of conventional methods and a 2 × 2 table for assessing test accuracy (i.e., sensitivity and specificity). In recent years, several statistical methods have been used to evaluate new tests when no or an imperfect gold/reference standard is available ^18-20.

VIA PROCEDURE²¹

When to Perform:
VIA can be performed at anytime during the menstrual cycle, including during menses (providing flow is not too heavy), during pregnancy, at a postpartum examination, or during a post abortion checkup. It can also be done when a woman comes for care related to STIs, HIV screening, or follow-up care. Most VIA programs recommend performing VIA screening on any sexually experienced woman age 30 or above, until the age of 40 to 50.

Preparing the Woman for VIA:
Health care providers need to provide a careful explanation of the procedure, why it is being done, what the possible findings might be, as well as what follow-up care might be necessary. A reproductive and health history should also be taken including menstrual history, bleeding pattern (irregular or post coital bleeding), parity, age, current pregnancy status or contraceptive method, and family history of mother or sister with cervical cancer. The woman should be draped with her own clothing or a sheet, if available, and placed on an examination table as comfortably as possible.

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Equipment Needed for VIA:

The following equipment is needed to perform VIA:

Report form or register to record the result
Examination table that enables the woman to position herself so that the clinician can insert a speculum and view the cervix
Adequate light source (halogen torch or flashlight)
Instrument tray
Cotton swabs
Vaginal speculum that can be locked open, leaving the examiner's hands free to adjust the light and swab the cervix
New examination gloves or high-level disinfected surgical gloves

VIA Procedure:
Following are steps that are essential to performing VIA:
1. Assemble equipment and arrange equipment on the tray.

2. Ensure that the light source is working.

3. Assist woman onto the examination table after she has emptied her bladder.

4. Put on gloves and arrange equipment on the tray.

5. Inspect the external genitalia for the presence of lesions, papules, vesicles, ulcerations, 6.Condylomata, discharge, redness, swelling, excoriation.

7. Tell the woman you will touch her. Check for inguinal lymph nodes.

8. Lubricate the speculum with clean, preferably warm, water.

9. Slowly and carefully insert the speculum without scraping the cervix with the bills.

10. Adjust the speculum, so the entire cervix is in view and adjust the light as needed.

11. Inspect the cervix for cervicitis, ectopy, nabothian cysts, ulcers, warts, polyps, leukoplakia (thickened, white patches), or tumors. Look for vesicles, small papules, or ulcers on the cervix.

12. Observe the size and shape of the cervix and the external os.

13. Check for signs of infection such as vaginitis, cervicitis, or mucopurulent discharge. 14. Use a dry cotton swab to wipe away any discharge, blood, or mucus from the cervix.

15. Identify the anterior and posterior lip of the cervix, red columnar epithelium, pink squamous epithelium, the squamocolumnar junction, and the transformation zone.

16. Observe all four vaginal fornices to make sure they are free from any growth.

17. Record any abnormal visual findings.

18. Soak a clean swab in 3% to 5% acetic acid and apply to the cervix liberally. Wait at least 1 full minute for the acetic acid to be absorbed (use a watch). Tell the woman that she might feel a slight burning sensation.

19. Check the transformation zone carefully, especially near the squamocolumnar junction, for any dense, non-movable acetowhite areas in the epithelium. Look around the entire transformation zone for any raised and thickened white plaques or acetowhite lesions. If acetowhite areas are identified, note the location, extension, intensity of whiteness, borders and demarcations, as well as size. Lesions vary in size, thickness, opacity, and border definition. Larger, thicker, more opaque lesions with clearly defined borders next to the squamocolumnar junction suggest more severe cervical disease.

Describing VIA Findings:
As explained previously, the results of VIA are reported as VIA-negative, VIA-positive, or suspicious for cancer. VIA-negative means there are no significant acetowhite lesions. It is the most challenging category in VIA because there are so many variations of acetowhite areas that can appear. There may be bluish white lesions or doubtful lesions without definite margins. Nabothian cysts and polyps may also turn acetowhite, but they are not precancerous lesions. There may be a faint line, appearing to be acetowhitening at the junction of columnar and squamous epithelium. There may be acetowhite lesions far away from the squamocolumnar junction or streak like acetowhitening. There may also be dot like areas on the columnar epithelium, which are due to areas of metaplasia and more diffuse acetowhitening with columnar epithelium staining with acetic acid. Figures 2 and 3 show some of the visual findings with negative VIA.

VIA negative. The mild acetowhite staining in a linear pattern at the lower edge of the squamocolumnar junction and around the two glandular crypt openings is the typical appearance of immature metaplasia.

VIA negative. The button-like, acetowhite area with ill-defined margins is due to a Nabothian follicle. Other ill-defined acetowhite areas are due to squamous metaplasia.

VIA positive. There is a moderately opaque, sharply bordered, wide band of acetowhite staining around the cervical os, touching the squamocolumnar junction. There is mild acetowhite staining of the immature metaplastic epithelium extending onto the endocervical polyp.

A positive test result means there are sharp, distinct, well-defined, dense (opaque/dull or oyster white) acetowhite areas, with or without raised margins, close to the squamocolumnar junction near the transformation zone. There may be dense acetowhite lesions in the columnar epithelium, near the os. Condyloma and leukoplakia close to the squamocolumnar junction turn intensely white with acetic acid. Findings that are suspicious for cancer include an ulcerative, proliferative growth that may bleed easily when touched. If there is doubt about the description or the outcome of the test, it can be gently repeated without inducing bleeding.

Findings must also be noted in a retrievable fashion such as the client register or log or the woman's book (if she has one), and a screening/referral card should be completed. On average about 15% to 20% of women are VIA-positive and are referred for additional diagnostic workup or treatment, depending on whether a single- or multiple-visit approach is being used. Test specificity (the ability to correctly identify a normal cervix) improves with clinician experience. The ability to identify an abnormal cervix or the sensitivity of VIA does not change much with practice. About 1 in 7 women who are VIA-positive have a high-grade cervical intraepithelial lesion that needs treatment.

What Does VIA Involve:
1. Performing a vaginal speculum exam during which a health care provider applies dilute (3-5%) acetic acid (vinegar) to the cervix.

2. Abnormal tissue temporarily appears white when exposed to vinegar.

3. Viewing the cervix with the naked eye to identify color changes on the cervix.

4. Determining whether the test result is positive or negative for possible precancerous lesions or cancer.

What Infrastructure Does VIA Require ^22-26
1. Private exam area

2. Examination table

3. Trained health professionals

4. Adequate light source

5. Sterile vaginal speculum

6. New examination gloves, or HLD surgical gloves

7. Large cotton swabs

8. Dilute (3-5%) acetic acid (vinegar) and a small bowl

9. Containers with 0.5% chlorine solution

10. A plastic bucket with a plastic bag

11. Quality assurance system to maximize accuracy

Categories For VIA Test Results:

VIA Category	Clinical Findings
Test-negative	No acetowhite lesions or faint acetowhite lesions; polyp, cervicitis, inflammation, Nabothian cysts
Test-positive	Sharp, distinct, well-defined, dense (opaque/dull or oyster white) acetowhite areas—with or without raised margins touching the squamocolumnar junction (SCJ); leukoplakia and warts.
Suspicious for cancer	Clinically visible ulcerative, cauliflower-like growth or ulcer; oozing and/or bleeding on touch.

1. Acetowhite area far from squamocolumnar junction (SCJ) and not touching it is insignificant.
2. Acetowhite area adjacent to SCJ is significant

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Test Performance: Sensitivity and Specificity:
Sensitivity:
1. The proportion of all those with disease that the test correctly identifies as positive.
Specificity:
2. The proportion of all those without disease (normal) that the test correctly identifies as negative.

Strengths of VIA:
1. Simple, easy-to-learn approach that is minimally reliant upon infrastructure.
2. Low start-up and sustaining costs.
3. Many types of health care providers can perform the procedure.
4. Test results are available immediately.
5. Requires only one visit.
6. May be possible to integrate VIA screening into primary health care services.

Limitations of VIA:
1. Moderate specificity results in resources being spent on unnecessary treatment of women who are free of precancerous lesions in a single-visit approach.
2. No conclusive evidence regarding the health or cost implications of over-treatment, particularly in areas with high HIV prevalence.
3. There is a need for developing standard training methods and quality assurance measures.
4. Likely to be less accurate among post-menopausal women.
5. Rater dependent.

CONCLUSION:
Although cytology-based screening programs using Pap smears have been shown to be effective in the United States and other developed countries, sustaining high-quality cytology-based programs is difficult in low-resource settings. Therefore, in settings where health care resources are scarce, they should be directed toward cost-effective strategies that are more affordable and for which quality can be assured.

The most efficient and effective strategy for detecting and treating cervical cancer precursors in low-resource settings is to screen using either VIA or HPV DNA testing and then to treat using cryotherapy (freezing). This strategy is optimally achieved in a single visit and can be carried out by competent physicians and non physicians, including nurses and midwives.

In conclusion, as a result of a demonstration project, visual inspection with acetic acid (VIA). VIA is an attractive alternative to cytology-based screening in low-resource settings. The alternative simple and safe cervical cancer-prevention techniques simplify the process and render it feasible and acceptable to women and providers in low-resource settings. Simple and inexpensive methods based on visual examination of the cervix are currently being investigated as alternative methods of cervical screening.

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