Summary | Introduction | Methods | Results | Discussion | References

Reprinted with permission from Elsevier (The Lancet, 2003, 361:814-820) (http://www.sciencedirect.com/science/journal/01406736)  

Royal Thai College of Obstetricians and Gynaecologists (RTCOG) and the JHPIEGO Corporation Cervical Cancer Prevention Group* (Members listed at end of paper)

Correspondence to: Dr Lynne Gaffikin, Cervical Cancer Prevention Programme, JHPIEGO Corporation, 1615 Thames Street, Suite 200, Baltimore, MD 21231, USA (e-mail:lgaffikin@jhpiego.net)

Summary

Background To increase screening and treatment coverage, innovative approaches to cervical-cancer prevention are being investigated in rural Thailand. We assessed the value of a single-visit approach combining visual inspection of the cervix with acetic acid wash (VIA) and cryotherapy.

Methods 12 trained nurses provided services in mobile (village health centre-based) and static (hospital-based) teams in four districts of Roi-et Province, Thailand. Over 7 months, 5999 women were tested by VIA. If they tested positive, after counselling about the benefits, potential risks, and probable side-effects they were offered cryotherapy. Data measuring safety, acceptability, feasibility, and effort to implement the programme were gathered.

Findings The VIA test-positive rate was 13·3% (798/5999), and 98·5% (609/618) of those eligible accepted immediate treatment. Overall, 756 women received cryotherapy, 629 (83·2%) of whom returned for their first follow-up visit. No major complications were recorded, and 33 (4·4%) of those treated returned for a perceived problem. Only 17 (2·2%) of the treated women needed clinical management other than reassurance about side-effects. Both VIA and cryotherapy were highly acceptable to the patients (over 95% expressed satisfaction with their experience). At their 1-year visit, the squamocolumnar junction was visible to the nurses, and the VIA test-negative rate was 94·3%.

Interpretation A single-visit approach with VIA and cryotherapy seems to be safe, acceptable, and feasible in rural Thailand, and is a potentially efficient method of cervical-cancer prevention in such settings.

Lancet 2003; 361: 814-820

Introduction

Worldwide, over 470 000 new cervical cancer cases occur yearly--about the same as the number of maternal deaths every year.^1,2 Tragically, although this disease is preventable by screening linked with treatment, most women die because few developing countries (where most cases arise) have successful prevention programmes, attributable in large part to the complex infrastructure needed for traditional cytology-based programmes.^3-6

To address this health inequity, effective practical alternatives to cytology for detection of precancerous lesions are being investigated. Research has established the viability of visual inspection with acetic acid (VIA) to identify precancerous lesions.^7-15 Besides its high sensitivity and low-cost, VIA is simple enough for nurses to provide at low levels of the health-care system, with locally available supplies. Because results are immediate, loss to follow-up is kept to a minimum.^5,16-18

Showing whether VIA can be efficiently and safely linked to treatment in low-resource settings is the logical next step in assessment of its potential role in developing country programmes. One way to achieve the best secondary prevention in low-resource settings is to couple testing with an immediate offer of diagnosis, treatment, or both for test-positive cases; essentially, a single-visit approach.¹⁹ A VIA-based, single-visit approach differs from the traditional approach in that diagnostic referral--eg, for colposcopy or biopsy--is restricted only to cases ineligible for treatment immediately post-testing.

Some people feel that this approach is inappropriate for developing countries, because the safety of non-physicians treating precancerous lesions in low-resource settings has never been established.²⁰ Additionally, writers of a Lancet Commentary¹⁵ noted that identification of many women with low-grade lesions (with VIA) might not be cost effective. To address these information gaps, a team from the USA (JHPIEGO Corporation) and Thailand (Royal Thai College of Obstetricians and Gynaecologists [RTCOG]), in collaboration with the Thai Ministry of Public Health (hereafter Ministry), initiated a multisite demonstration project in rural Thailand, where screening coverage remains low. The project aimed to establish the safety, acceptability, and feasibility of efficiently implementing a VIA and cryotherapy-based, single-visit approach to cervical-cancer prevention in a rural, low-resource setting. Cryotherapy was selected because it: has a cure rate comparable to other common outpatient procedures;^21-23 is easily learned; does not need electricity; requires few consumables; has a documented history of low complication rates;^22,24 and has an established performance record in the hand of non-physicians in developed countries.²⁵ We describe key results of this demonstration project with an alternative, field-based, resource-appropriate approach to cervical-cancer prevention.

Methods

The project was done in four districts in Roi-et Province, Thailand, because it is mostly rural, services have been unsuccessful here in the past, and a tertiary referral facility is reasonably close (Ministry of Public Health). The project recruited women between February, 2000, and October, 2000, and was approved by two Institutional Review Boards (Johns Hopkins Bayview Medical Center, USA, and Ministry of Public Health, Thailand), and received official support of the Ministry.

Provider training

12 nurses with some reproductive health experience were trained in VIA and cryotherapy during a 2-week, competency-based course with classroom and clinical practice (supervised by experienced US and local medical consultants). Sufficient practice was provided for everyone to be assessed as competent according to guidelines agreed upon by participating institutions.²⁶ Four skilled colposcopists who provided intensive nurse supervision during the project received similar training.

Project sites

Three nurses provided services at their hospital (static services) or as two-person, itinerant teams that regularly visited 36 rural primary health centres in the hospital catchment area (mobile services).

Screening participant selection criteria

The project targeted women aged 30-45 years, since its focus was to identify and treat precancerous lesions.¹⁶ Women with a total hysterectomy, history of cervical cancer, or more than 20 weeks pregnant (by clinical examination) were also excluded. Eligible women attending selected sites for any reason during recruitment were invited to participate. Ministry volunteers who routinely do health promotion activities in catchment villages provided information about the project by distributing brochures, by telling women about the services, and through loudspeaker announcements.

Sample size

A key question about cryotherapy use in low-resource settings is its safety when provided by non-physicians. Clinical experience with cryotherapy in developed countries has been associated with a low complication rate (<5%), which we anticipated would also be the case in Thailand. To ensure that we could detect a complication rate as low as 4% (with 2% precision), we estimated that 370 women needed treatment and 3700 women needed recruiting (assuming a 10% minimum test-positive rate).⁴ To allow for mobile-specific versus static-specific estimates, the final targeted sample size was 740 treated and 7400 tested.

Clinical protocol

At the intake visit, interested women participated in a group education session. Subsequently, a clinical history (including demographic and reproductive health questions) was taken. Women were individually counselled again, and written informed consent was obtained before testing.

After being positioned on the examination table, abdominal and external genitalia examinations were done, a Graves speculum was inserted, and the cervix was brought into view. The nurse then assessed the cervix for the presence of gross lesions consistent with possible cancer. Next, a dilute (5%) acetic acid solution was applied liberally to the cervix. After waiting 1 min, the cervix was re-examined by flashlight or an examination light. Special attention was paid to ensuring that the entire squamocolumnar junction was visualised. Assessment findings were recorded with standardised VIA categories (panel).

 

Project VIA categories and their relation to clinical findings
VIA category	Clinical findings
Test-positive	Raised and thickened white plaques
Test-negative	Smooth, pink, uniform, and featureless; ectopy, polyp, cervicitis, inflammation, Nabothian cysts
Cancer	Cauliflower-like growth or ulcer; fungating mass
Indeterminate	No distinct acetowhite lesion is visible, but some white area is apparent that could represent an abnormality Or, cervicitis or inflammatory changes are so severe that the cervix cannot be adequately assessed for acetowhite lesions

 

Test-positive women with lesions meeting four criteria were deemed eligible for immediate cryotherapy: not suspicious for cancer; did not extend onto the vaginal wall; occupied less than 75% of the cervix; and extended less than 2 mm beyond the cryotherapy probe. To conform with Thai clinical guidelines, additional criteria for postponement of immediate treatment, referral, or both included: menses--current or expected within 7 days (treatment postponed until after menses); HIV--known positive status (follow-up provided by a referral physician); polyp--protruding into the cervical os (polyp removed by a referral physician, after which the patient was to return to the nurse for cryotherapy); fibroid--tumours more than 12 weeks' size (woman referred to a physician; if not a candidate for hysterectomy, she was to return to the nurse for cryotherapy).

Women assessed as indeterminate with one or more of the following risk factors were also offered treatment: sister or mother had cervical cancer; previous abnormal pap; early sexual onset; smoker; HIV positive; or previous history of a sexually transmitted disease.

Before treatment, the nurse explained the meaning of the test results, the treatment procedure, potential risks, benefits, side-effects, and advantages and disadvantages of immediate (versus postponed) treatment. Then, the woman made an informed choice about whether or not she wanted immediate treatment. Test-positive women with evidence of purulent cervicitis, otherwise eligible for immediate treatment, got one oral dose of two antibiotics before cryotherapy to reduce the risk of pelvic infection post-treatment.

Cryotherapy was provided with a standard double-freeze technique and a 19-mm probe with a shallow nipple (Wallach Scientific, CT, USA). Oral non-narcotic analgesics were offered to women with bothersome cramping after treatment. Before leaving, treated women were given home self-care instructions and were told when to return for their next visit. Women were instructed to return immediately if they had any symptoms of a potential complication--eg, fever for more than 2 days. Finally, women were counselled to abstain from sexual intercourse for at least 4 weeks after treatment and were given 20 condoms to reduce the risk of infection, if intercourse could not be avoided.

The first follow-up visit (at 3 months) was to inquire about the woman's post-treatment experience--eg, when watery discharge ceased--and any post-treatment problems. Nurses did a pelvic examination only to investigate a specific complaint. A 1-year follow-up visit was for pelvic and speculum examinations to assess the general state of the cervix and a VIA test to determine whether any acetowhite lesion was present. Anyone who was VIA-positive at 1 year was referred to a physician for further assessment.

Outcome measures

Project indicators represented four basic themes: safety, acceptability, feasibility, and programme effort. Specific indicators measured were as follows.

Safety--(1) proportion having severe bleeding, shock, or any disorder needing admission during treatment; (2) proportion with post-cryotherapy complications; and (3) proportion returning for a problem visit.

Acceptability--(1) proportion satisfied with their initial visit decisions; (2) proportion whose partner supported their treatment decisions; and (3) proportion who successfully adhered to home-care instructions.

Feasibility--(1) recruitment rate; (2) cryotherapy rate; (3) proportion of cryotherapy procedures postponed versus provided immediately; and (4) time-trend correlation between VIA and family planning visits.

Programme effort--(1) VIA test-positive rate 1 year post-cryotherapy; (2) VIA coverage rate; and (3) correlation between provider and supervisor VIA assessment findings.

Role of the funding source

The sponsors of this study had no role in study design, data collection, data analysis, data interpretation, writing of the report, or in the decision to submit the report for publication.

Results

5999 women were VIA tested (figure 1); they were mean age 36·7 years (SD 4·35) and had 5·6 years of education (SD 2·74). 5837 (97·3%) were married or cohabiting with a partner. More than half (3516; 58·6%) received mobile services in a primary centre; the others received services at a district hospital. 798 (13·3%) were VIA positive. The test-positive rate did not differ significantly between static and mobile services (13·9% vs 12·9%, respectively; p=0·23). However, it did differ significantly by district (p<0·0001). 51 patients (0·9%) were classified as indeterminate and four (<1%) had suspect cancer.

738 (92·5%) women who were VIA positive, and 18 who were indeterminate, received cryotherapy (figure 1). Of the four suspect cancers, all were followed up with colposcopy or biopsy at the referral hospital; one cancer was confirmed (stage 2B, poorly differentiated squamous cell carcinoma). This finding yields a cancer rate of 16·7 per 100000 women, similar to the age-adjusted cancer rate (18 per 100000) for nearby Khon Kaen Province, as reported by the International Agency for Research on Cancer. The other women with suspect cancers had cervicitis.

Of those treated with cryotherapy, 629 (83·2%) returned for their scheduled first visit. No significant difference existed in mean age or education level (p=0·35 and p=0·95, respectively) between those returning and not returning. However, the proportion returning did differ significantly by district (p<0·0001) and between mobile and static sites (86·4% and 78·8%, respectively; p=0·01). A higher proportion (707; 93·5%) returned for their 1-year than their first follow-up visit.

With respect to safety of cryotherapy, of 290 women reporting some pain during the procedure, it was mild for 229 (79%), moderate for 53 (18·3%), and severe for eight (2·8%). An analgesic was provided after the procedure to 46 (6·2%) of 746 women. Immediately post-treatment, 307 (40·8%) reported pain, although 247 (80·4%) of these said it was mild. 11 women had mild bleeding during the procedure, which was managed by applying pressure; no surface medication (eg, Monsel's solution) was applied. No admissions and no outpatient clinical action, other than pressure, were needed immediately post-treatment.

33 (4·4%) of 756 women returned for an unscheduled (problem) visit. An outpatient procedure--a conservative proxy measure for minor complications--was done for 17 (51·5%) of those returning (2·2% of those treated). Very few women (n=7) complained about discharge or spotting. No major complications (admission, transfusion, or major surgery) were reported. One woman had suspect pelvic inflammatory disease but did not need admission or intravenous antibiotics. Systems were instituted to actively monitor whether women presented with cryotherapy-related problems elsewhere. Some problem visits might have gone unreported but, in view of the high project visibility, any important complication is unlikely to have gone unnoticed. 100 (16%) of the 624 women returning at the first follow-up visit post-treatment had a complaint (table 1), most typically pain or cramping (n=71).

With respect to acceptability of the single-visit approach, women reported being highly satisfied at the end of their initial visit (table 2). Almost all (5136/5146; 99·8%) women who had a negative VIA test said they would recommend it, and 737 (97·5%) of the 756 women treated indicated they would recommend both VIA and cryotherapy. At 3 months, 97·9% (616/629) had recommended VIA to others and 94·5% (594/629) said that treatment was equal to or better than expected.

Rates of adherence to home-care requirements were impressively high. Although 454/628 (72·3%) reported having intercourse post-treatment, 312 (68·9%) of 453 initiated intercourse after 4 weeks. Of the remaining 140 (31·1%), 124 (88·6%) used condoms and almost all reported consistent condom use. Overall, only 16/627 (2·6%) had unprotected intercourse within 1 month post-treatment (4·3% [27/624] including those inconsistently using condoms).

Initially, 697 (92·2%) of those treated thought abstaining from intercourse for 4 weeks would not be a problem for their husband. Few (45/628; 7·2%) at first follow-up indicated having problems convincing their husband to postpone intercourse. Of those having intercourse (454), only 13 (2·9%) reported problems convincing their husband to use condoms. Many (596/628; 94·9%) at this visit reported husband satisfaction with their decision to get treated. Of those having intercourse within 1 month, 128 (92·8%) did so because of their husband. After a few weeks, the nurses reported feeling very confident about their testing and treatment skills and positive about VIA and the single-visit approach.

With respect to feasibility of the single-visit approach, about 75% (4499/5999) of the women were tested within the first 3 months, probably because of supplemental outreach village education and awareness efforts by Ministry staff. Once most of the targeted sample size had been achieved, these efforts were discontinued, and VIA recruitment in the latter months was promoted via provider or woman word of mouth.

610 test-positives and eight indeterminates were eligible for immediate treatment. Eligibility did not differ significantly between mobile and static users (p>0·99), nor by mean age or education level (p=0·83 and p=0·54, respectively). 115 test-positives were eligible for cryotherapy but at a later date (postponed). The main reason for postponement was menses. Few (n=10) postponements were for clinic problems (eg, no equipment or supplies). 14 test-positives were told to return for cryotherapy after seeing a referral physician, 42 and 13 women with a positive test were totally ineligible due to lesion size and gynaecological problems, respectively, and four test-positives were referred for reasons unrecorded. Overall, 79 women were referred (73 test-positives, four suspect cancers, and two indeterminates). Of those ultimately treated (n=756), 615 (81·3%) received cryotherapy immediately. 609 of 618 judged eligible by the nurse for immediate cryotherapy received it immediately.

To assess the project's possible effect on other hospital outpatient reproductive health services, time trends were compared (Pearson's correlation) between family planning visits in 1999 and 2000 and VIA visits during the project (figure 2). No significant linear correlation was noted between the two time trends (r=0·4; p=0·12).

The 1-year VIA test-negative rate was 94·3%. One woman had an indeterminate test and one had suspect cancer (later confirmed as adenocarcinoma in a polyp, stage 1A). No squamous cell cancers were identified at 1 year. During recruitment, 1·5% of eligible women in Roi-et Province were VIA tested. Coverage varied substantially by district (table 3).

Assessments done independently by supervisors and providers for the same woman during supervisory visits were highly correlated (table 4), suggesting nurses did VIA competently and followed clinical protocol appropriately.

	Percentage agreement (95% CI)		p	Matched pairs
Result indicator
VIA assessment	92·94	0·8013	<0·0001	85
category	(92·85-93·03)
Case management	91·67	0·8017	<0·0001	72
decision	(91·59-91·75)
Table 4: Supervisory visit co-assessment

Next Page

| Home | Family Planning | Maternal & Neonatal Health | Cervical Cancer |  Related Health Topics | 
Tools for Trainers | Reading Room | Related Links | Search ReproLine | Website Tools

Website design copyright © 1995-2003 by JHPIEGO Corporation. All rights reserved.

Last Updated: 09 Jul 2003

URL: http://www.reproline.jhu.edu/
Reproductive Health Online (ReproLine): a family planning and reproductive health training website