Screening for cervical Screening for cervical neoplasia in Bangladesh neoplasia in Bangladesh using visual inspection using visual inspection

with acetic acidwith acetic acidChairperson: Chairperson: Dr. Gopal Chandra Das Dr. Gopal Chandra Das

Assistant Professor Assistant Professor Department of Obs & Gynae, Department of Obs & Gynae,

MMCMMCSpeaker: Speaker:

Dr. Khurshida Jahan Dr. Khurshida Jahan MS Obs & Gynae (Thesis part), MS Obs & Gynae (Thesis part),

MMC MMC

Auther:Auther: NessaNessa A A, , HussainHussain MA MA, , RahmanRahman JN JN, ,

Rashid MHRashid MH, , MuwongeMuwonge R R, , SankaranarayananSankaranarayanan R R..

Department of Obstetrics & Gynecology, Bangabandhu Department of Obstetrics & Gynecology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.Sheikh Mujib Medical University, Dhaka, Bangladesh.

Source:Source: International Journal of Gynaecology & Obstetrics. 111(2010) 115-International Journal of Gynaecology & Obstetrics. 111(2010) 115-

118. 118.

IntroductionIntroduction Cervical cancer constitutes 25% Cervical cancer constitutes 25%

of all cancer cases in women and of all cancer cases in women and accounts for 13000 new cases accounts for 13000 new cases and 8000 deaths annually in and 8000 deaths annually in Bangladesh. More than 80% of Bangladesh. More than 80% of patients diagnosed with this patients diagnosed with this eminently preventable cancer eminently preventable cancer present in clinically advanced, present in clinically advanced, inoperable stages. inoperable stages.

The aim of the present paper was The aim of the present paper was to briefly describe the to briefly describe the organization and functioning of organization and functioning of the VIA screening program and the VIA screening program and discuss the early results, discuss the early results, strengths and limitations of the strengths and limitations of the pioneering effort in cervical pioneering effort in cervical cancer prevention in Bangladesh.cancer prevention in Bangladesh.

Objective:Objective: To report the organization and To report the organization and

early results of a visual early results of a visual inspection with acetic acid (VIA) inspection with acetic acid (VIA) screening program for cervical screening program for cervical cancer prevention in cancer prevention in Bangladesh. Bangladesh.

Patients and Patients and methodsmethods

The VIA screening program is provided The VIA screening program is provided through the existing healthcare through the existing healthcare infrastructure in Bangladesh. infrastructure in Bangladesh.

The target population for VIA screening The target population for VIA screening is apparently healthy, ambulant, is apparently healthy, ambulant, married women aged 30 years and married women aged 30 years and above attending the healthcare facilities above attending the healthcare facilities at MCWCs, DHs, MCHs, BSMMU, at MCWCs, DHs, MCHs, BSMMU, UHFWCs, and UHCs. UHFWCs, and UHCs.

It was an opportunistic screening program. It was an opportunistic screening program. The screening algorithm involved a single The screening algorithm involved a single visit for screen-negative women and 2-3 visit for screen-negative women and 2-3 visits for screen-positive women, visits for screen-positive women,

After counseling and informed consent, a After counseling and informed consent, a speculum examination was performed for speculum examination was performed for direct visualization of the cervix and direct visualization of the cervix and vagina to identify the squamocolumnar vagina to identify the squamocolumnar junction (SCJ), inflammation, polyps, junction (SCJ), inflammation, polyps, leukoplakia, and growth. Freshly prepared leukoplakia, and growth. Freshly prepared 5% 5% dilute acetic acid was applied to the dilute acetic acid was applied to the cervix. cervix.

Care was taken to avoid any Care was taken to avoid any bleeding and results were reported 1 bleeding and results were reported 1 minute after application under 100-minute after application under 100-watt illumina tion. VIA test was watt illumina tion. VIA test was considered positive when a definite, considered positive when a definite, well-defined acetowhitening was well-defined acetowhitening was observed in the transformation zone observed in the transformation zone in close proximity with the SCJ or in close proximity with the SCJ or when a growth turned acetowhite; when a growth turned acetowhite; when in doubt the test was repeated. when in doubt the test was repeated.

All VIA-positive women were referred All VIA-positive women were referred with a pink referral card to the with a pink referral card to the colposcopy clinics at BSMMU or nearby colposcopy clinics at BSMMU or nearby medical college hospitals. Women with medical college hospitals. Women with negative VIA were given a blue card negative VIA were given a blue card and advised to come back after 3 years. and advised to come back after 3 years. A manual register is kept at each VIA A manual register is kept at each VIA screening center that provides the screening center that provides the number of women screened, tested number of women screened, tested positive, and tested negative.positive, and tested negative.

Colposcopy was performed by the trained Colposcopy was performed by the trained colposcopist when the screen-positive colposcopist when the screen-positive women reported at the colposcopy clinics women reported at the colposcopy clinics at medical college hospitals or BSMMU. at medical college hospitals or BSMMU. All women with suspected CIN and All women with suspected CIN and cancer had colposcopy-directed cervical cancer had colposcopy-directed cervical biopsy and the specimens were given to biopsy and the specimens were given to the women or their attendants to submit the women or their attendants to submit to the histopathology department. The to the histopathology department. The colposcopic findings were documented in colposcopic findings were documented in a form. a form.

Women with normal histology and CIN 1 reports Women with normal histology and CIN 1 reports were advised to return for follow-up after 6-12 were advised to return for follow-up after 6-12 months. Women with CIN 1 who wanted months. Women with CIN 1 who wanted immediate treatment or who were unlikely to immediate treatment or who were unlikely to report for follow-up and those above 35 years report for follow-up and those above 35 years were treated with cryotherapy or LEEP. Women were treated with cryotherapy or LEEP. Women with histologically confirmed CIN 2 or 3 lesions with histologically confirmed CIN 2 or 3 lesions were treated with LEEP or cryotherapy and were were treated with LEEP or cryotherapy and were advised to return for follow-up after 6 months. advised to return for follow-up after 6 months. Women with cervical cancer were referred to Women with cervical cancer were referred to cancer treatment facilities for further cancer treatment facilities for further investigations and treatment.investigations and treatment.

The final diagnosis was based on the The final diagnosis was based on the histopathology or colposcopy if no or an histopathology or colposcopy if no or an inadequate biopsy sample was taken.inadequate biopsy sample was taken.

ResultsResults From January 1, 2005, to June 30, From January 1, 2005, to June 30,

2008, VIA screening was provided 2008, VIA screening was provided

for 104 098 women in 44 districts in for 104 098 women in 44 districts in

Bangladesh. The average number of Bangladesh. The average number of

women screened in most districts women screened in most districts

ranged from 800-4000 women. ranged from 800-4000 women.

Table 1: Number of women screened & those tested

positiveYear of screening Number screened Screen positive (%)

2005 11693 548 (4.7)

2006 21609 925(4.3)

2007 40785 1918(4.7)

2008 until June 30011 1622(5.4)

Total 104098 5013(4.8)

Of the women screened, 5013 (4.8%) Of the women screened, 5013 (4.8%) were positive on VIA and were were positive on VIA and were referred to colposcopy clinics at referred to colposcopy clinics at BSMMU or nearby medical college BSMMU or nearby medical college hospitals.hospitals.

Overall, 4371 (87.2%) of screen Overall, 4371 (87.2%) of screen positive women underwent positive women underwent colposcopy. colposcopy.

Table 2: Distribution of women Table 2: Distribution of women attending different colposcopy clinics.attending different colposcopy clinics.

Institutes with colposcopy clinics No. (%) of women

Bangabandhu Sheikh Mujib Medical University (BSMMU) 2188 (43.6)

Chittagong Medical"College Hospital (CMCH) 747 (14.9)

Rajshahi Medical College Hospital (RjMCH) 442 (8.8)

Mymensingh Medical College Hospital (MMCH) 341 (6.8)

Ktmlna Medical College Hospital (KMCH) 277 (5.5)

Sylhet MAG Osmani Medical College Hospital (SMAGOMCH) 210 (4.2)

Dhaka Medical College Hospital (DMCH) 132 (2.6)

Rangpur Medical College Hospital (RMCH) 34 (0.7)

Women who did not attend 642 (12.8)

Total 5013 (100.0)

Total women underwent colposcopy – 4371 Total women underwent colposcopy – 4371 Women attended at BSMMU (VIA +ve cases) Women attended at BSMMU (VIA +ve cases)

– 2188 – 2188 Normal colposcopic findings – 1044 (47.7%) Normal colposcopic findings – 1044 (47.7%) Colposcopic abnormalities Colposcopic abnormalities

Suggestive of CIN or cancer Suggestive of CIN or cancer =1144 =1144 CIN I CIN I = 682 = 682 CIN IICIN II = 149 = 149 CIN III CIN III = 29 = 29 Invasive Invasive = 134 = 134 Unsatisfactory Unsatisfactory = 150 = 150

Histopathology results of cases Histopathology results of cases with colposcopic abnormalitieswith colposcopic abnormalities CINI CINI = 369 = 369 CIN II CIN II = 127 = 127 CIN III CIN III = 30 = 30 Invasive cancer Invasive cancer = 123 = 123

Of the 4371 women who underwent Of the 4371 women who underwent colposcopy, 2188 attended the colposcopy colposcopy, 2188 attended the colposcopy clinic at BSMMU. The results of colposcopy clinic at BSMMU. The results of colposcopy and histology are given in Table 3. No and histology are given in Table 3. No colposcopic abnormalities were detected in colposcopic abnormalities were detected in 1044 (47.7%) women, whereas directed 1044 (47.7%) women, whereas directed biopsies in 1144; women showed colposcopic biopsies in 1144; women showed colposcopic abnormalities suggestive of CIN or cancer. abnormalities suggestive of CIN or cancer. On histology, 369 women were diagnosed On histology, 369 women were diagnosed with CIN 1, 127 with CIN 2, 30 with CIN 3, with CIN 1, 127 with CIN 2, 30 with CIN 3, and 123 with invasive cancer. and 123 with invasive cancer.

VIA repeated by gynecologists in 2188 VIA repeated by gynecologists in 2188 women before they underwent women before they underwent colposcopy was positive in 1060 and colposcopy was positive in 1060 and negative in 1128 women; the final negative in 1128 women; the final diagnosis among these 1128 VIA-diagnosis among these 1128 VIA-negative women was as. follows: no negative women was as. follows: no lesion (n = 1091); CIN 1 (n = 22); CIN lesion (n = 1091); CIN 1 (n = 22); CIN 2-3 (n = 10); and invasive cancer (n = 2-3 (n = 10); and invasive cancer (n = 5). 5).

The sensitivity, specificity, and positive The sensitivity, specificity, and positive predictive value of VIA to detect CIN 2 predictive value of VIA to detect CIN 2 and 3 lesions after excluding the 123 and 3 lesions after excluding the 123 invasive cancer cases in this selected invasive cancer cases in this selected sample of women were 93.6%, 58.3%, sample of women were 93.6%, 58.3%, and 15.6%, respectively (Table 4). and 15.6%, respectively (Table 4).

Forty-one women (11%) with CIN 1 Forty-one women (11%) with CIN 1 and 80 women (50%) with CIN 2-3 and 80 women (50%) with CIN 2-3 lesions received treatment with LEEP lesions received treatment with LEEP (n = 105), cryotherapy (n = 6), or (n = 105), cryotherapy (n = 6), or hysterectomy (n= 10) at BSMMU.hysterectomy (n= 10) at BSMMU.

Table 3 Accuracy of visual screening with Table 3 Accuracy of visual screening with acetic acid to detect CIN 2-3 lesions among acetic acid to detect CIN 2-3 lesions among 2065 women attending colposcopy services 2065 women attending colposcopy services

at BSMMU.at BSMMU.VIA result Women detected

with CIN 2-3 lesionsWomen with normal cervix or CIN 1 lesions

Total

Positive 147 795 942

Negative 10 1113 1123

Total 157 1908 2065

Sensitivity: 93.6% (95% CI, 88.6-96.9); Specificity: 58.3% (95% CI, 56.1-60.6); Positive predictive value: 15.6% (95% CI, 13.3-18.1); Negative predictive value: 99.1% (95% CI, 98.4-99.6).

DiscussionDiscussion Among the cancers, cervical cancer accounts Among the cancers, cervical cancer accounts

for almost one fifth of cases in women. The for almost one fifth of cases in women. The cervical cancer burden is closer to that of cervical cancer burden is closer to that of maternal deaths (13 000 deaths) in maternal deaths (13 000 deaths) in Bangladesh. Currently, 32 million women Bangladesh. Currently, 32 million women are aged between 30 and 60 years and less are aged between 30 and 60 years and less than 0.4% are screened annually with a Pap than 0.4% are screened annually with a Pap smear. It is not feasible to introduce cytology smear. It is not feasible to introduce cytology screening for cervical cancer control in screening for cervical cancer control in Bangladesh given the resource constraints. Bangladesh given the resource constraints.

The VIA test positivity of around 5% in this The VIA test positivity of around 5% in this program was at the lower range of test program was at the lower range of test positivity reported in other VIA studies in positivity reported in other VIA studies in Asia and Africa. Asia and Africa.

On repeat VIA performed before colposcopy, On repeat VIA performed before colposcopy, a little more than half of the women were a little more than half of the women were scored as negative, which indicates the wide scored as negative, which indicates the wide variability between the test providers due to variability between the test providers due to the subjective interpretation of the test. the subjective interpretation of the test.

If we extrapolate this finding to the entire If we extrapolate this finding to the entire study, the test-positive rates are likely to be study, the test-positive rates are likely to be even lower than 5%. even lower than 5%.

Treatment coverage of women with high-Treatment coverage of women with high-grade cervical cancer precursors is grade cervical cancer precursors is inadequate: half of such women received inadequate: half of such women received treatment at the BSMMU colposcopy clinic. treatment at the BSMMU colposcopy clinic.

The treatment rates can be improved if The treatment rates can be improved if cryotherapy or LEEP are offered cryotherapy or LEEP are offered immediately following colposcopy at the immediately following colposcopy at the first visit instead of receiving treatment first visit instead of receiving treatment after histopathology confirmation of punch after histopathology confirmation of punch biopsy specimens at the second visit. biopsy specimens at the second visit.

Moreover, the current VIA-based program Moreover, the current VIA-based program would facilitate the devel opment of would facilitate the devel opment of screening, diagnosis, and treatment screening, diagnosis, and treatment infrastructure in health services, improve infrastructure in health services, improve awareness of cervical cancer prevention awareness of cervical cancer prevention among the population, and enable among the population, and enable incorporation of new developments such as incorporation of new developments such as the more accurate, objective & affordable the more accurate, objective & affordable HPV testing technologies when these HPV testing technologies when these technologies are commercially available & technologies are commercially available & affordable for wider use in public health affordable for wider use in public health services. services.

CONCLUSION:CONCLUSION: A VIA-based program would A VIA-based program would

facilitate the development of facilitate the development of screening, diagnosis, and screening, diagnosis, and treatment of cervical neoplasia and treatment of cervical neoplasia and improve awareness of cervical improve awareness of cervical cancer prevention in Bangladesh.cancer prevention in Bangladesh.

Approximate rates of spontaneous Approximate rates of spontaneous regression, persistence & regression, persistence &

progression of CIN progression of CIN CINI CINI CINII CINII CINIII CINIII

Regression to normal Regression to normal 60% 60% 40% 40% 30% 30%

Persistence Persistence 30% 30% 35% 35% 48% 48%

Progression to CINIII Progression to CINIII 10% 10% 20% 20% - -

Progress to carcinoma Progress to carcinoma <1% <1% 5% 5% 22% 22%

VIA & Colposcopy in MMCH VIA & Colposcopy in MMCH 2010 2010

Total VIA done Total VIA done - 3214 - 3214 VIA –ve VIA –ve - 3139 - 3139 VIA +ve VIA +ve - 75 - 75

Total colposcopy done Total colposcopy done - 433 - 433 Normal Normal - 200 - 200 CINI CINI - 172 - 172 CINII CINII - 22 - 22 CINIII CINIII - 08 - 08 Unsatisfactory Unsatisfactory - 11 - 11 Invasive Invasive - 20- 20

Histopathology results of Histopathology results of cases with colposcopic cases with colposcopic

abnormalities in MMCH abnormalities in MMCH CIN I CIN I 92 92

CIN II CIN II 4545

CIN III CIN III 15 15

Invasive carcinoma Invasive carcinoma 15 15

Squamous epithelium Columnar epithelium

Colpoccopy – Abnormal Findings