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��ࡱ�>��	�����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������[�	��0nbjbj����	gΐΐnw�������rr�����d������T�/�!!!!!hhh%/'/'/'/'/'/'/$R1��30K/�hhhhhK/��!!G`/�(�(�(h�	�!�!%/�(h%/�(�(�+,!����@����!V�+/v/0�/�+,$6d#V$6,,"$6�),�hh�(hhhhhK/K/�%"hhh�/hhhh��������������������������������������������������������������������$6hhhhhhhhhr	{:	CAN VISUAL INSPECTION WITH ACETIC ACID BE USED AS AN ALTERNATIVE TO PAP SMEAR IN SCREENING CERVICAL CANCER?   
Hend S. Saleh
Obstetrics and Gynecology Department, Faculty of Medicine Zagazig University
ABSTRACT
Objective: to evaluate the value of visual inspection with acetic acid (VIA)in screening cervical cancer in comparison to Pap smear. 
Material And Methods: 200 women  attending the obstetric and gynecology Department in Zagazig university hospital from December 2011 to November 2012.They were screened using Pap smear and VIA . Colposcopy was done for all women .Those found positive on any screening test were subjected to cervical biopsy. The results were analyzed for Pap smear and VIA. The statistical tests and results were computed using SPSS version 12. 
Results: out of 200 patients, acetic acid (VIA) was positive in  24 (12%) patients and Pap smear was abnormal in 8 (4%). There were 5  LSIL,2 HSIL and one with cells suspicious of malignancy .Colposcopy was done in all 200 patients and scored to Reid's colposcopic index . Colposcopy was recorded abnormal in 35 cases (17.5) .18 cases (51.4%) had a Reid score of 0-2 and considered negative .17 cases (48.6%) had a positive colposcopy (Reid 3-8).Cervical biopsy was done on all 35 cases.  44% biopsies were positive and 56% were negative .15 positive biopsies incorporated 11 mild dysplasia,2 moderate dysplasia,1 sever dysplasia and one carcinoma in situ. The Pap smear had a sensitivity of 50.1%, specificity of 93.1%, and positive predictive value  of  89.3%    and negative predictive value of  65.6 %     .VIA had a sensitivity of  90%, specificity of 37 %      ,and positive predictive value of 52% and negative predictive value of 81%.
Conclusion: VIA is a good screening test as it is simple test ,has low cost and high sensitivity in comparison to Pap smear. So, It can be used as alternative  screening modality for cervical cancer in low resource locations. 
Key words: Cervical cancer, VIA, Pap smear, screening, developing countries          	INTRODUCTION
With the change in the life styles and demographic profiles of developing countries, non communicable diseases are emerging to be important health problems that demand appropriate control program before they assume epidemic proportion. One of these is the problem of cancer(1). Cervical cancer is the second most common gynecologic cancer world wide ,accounting for 13% of all female cancer in developing countries(2). The important reasons for higher cervical cancer incidence in developing  countries  are lack of resources , lack of effective Screening programs And poor organized healthy system aimed for detecting precancerous condition before they progress to invasive cancer .So , there is need of low cost approach For effective cervical cancer screening programs(3). Cevical cancer is a disease that can be prevented through both primary prevention and early detection . So in developed countries the incidence of cervical cancer has decreased due to screening, early detection and treatment .However in developing countries, 80% of cervical cancers are incurable at the time of detection due to their advanced stage(4). Several screening modalities are now available for early detection of cervical cancer and its precursor lesions. They all differ with regard to their test characteristic, feasibility and economic considerations. The different screening modalities have been cytology or Pap smear , visual inspection , using acetic acid (V I A) or Lugols iodine ,VIA with magnification (VIAM) and high risk human papilloma virus (HPV) screening(5). Cytologic methods of screening for cervical cancer ,precursors have become the main stay of population based prevention programs resulting in substantial reduction of disease in developed countries where mass screen is systemic rather than opportunistic(6).
The Papanicolaous (PAP) smear is a simple ,safe, non invasive and effective method for detection of precancerous ,cancerous and noncancerous changes in the cervix and vagina(7). Although this effectiveness of (PAP) smear, sustaining high-quality cytology based program is difficult  in low �resource setting due to its complex process of collection the sample ,preparation , staining ,reading ,reporting and the delay between screening and PROVISION of test results. So, in these areas it should be directed toward cost-effective strategies  that are more inexpensive and their qualities can be trusted (8).An alternative test is visual inspection of the cervix with Acetic acid (VIA). It has been advocated as an alternative screening method to PAP smears in developing countries(9). The attractive features of VIA include low cost ,simple administration ,real-time screening of results and accuracy comparable to good quality PAP smears. In developing nation ,resources are limited  so, VIA as a visual screening test does not depend on laboratory services  would be a possible an promising  alternative screening tool for early detection of cervical cancer(10,11). This study was designed to evaluate the clinical performance of visual inspection with acetic acid (VIA) as a simple test and if it is  a suitable alternative to PAP smear for early detection of cervical cancer .
MATERIAL AND METHODS
In this prospective clinical comparative study 200 women of age group between 22 to 50 years attending the obstetric and gynecology Department in Zagazig university hospital from December 2011 to November 2012 were included .All women enrolled in the study gave informed consent .They came presenting with history of any or all of the following ;Discharge per vagina , intermenstrual bleeding , post coital bleeding ,clinically suspicious looking cervix . Pregnant patients, patients with active bleeding per vagina, patients with frank growth on the cervix ,patients with history of total hysterectomy ,allergy to acetic acid or previous history of treatment of cancerous lesions . After obtaining a detailed history ,all patients were subjected to a general and local examination .Vulva was examined for any warts ,ulcer or infection . Cusco ,,s speculum was inserted for examination of vagina and cervix. The colour and smell of any discharge was noted .any discharge ,blood or mucus from cervix was removed by cotton swabs . A PAP smear was taken using Ayre's spatula by scrapping the squamocolumner junction gently throughout its circumference  with hooked end of Ayre's spatula .The PAP smear was prepared by transferring the materials obtained on Ayres' s spatula on a glass slides . Two such smears were  immediately fixed in 95% alcohol to stain them by papanicolau stain after that. The PAP was reported in the following 4 categories : Negative for neoplastic cellular changes ,atypical squamous cells for undetermined significance ,low-grade (LSIL) and high-grade intraepithelial lesion or worse (HSIL +) (12).A solution of 5% acetic acid was then applied to cervix using a cotton swab and after one minute visual inspection of cervix was done for development of any acetowhite area near squamocolumnar junction or close to external os or presence of aceto- white growth.The VIA results were interpreted as positive with detection of any distinct, opaque, dense or well defined aceto-white area  but if no aceto-white area were recorded or if a whitish appearance was doubtful,the test result was considered negative as when there is more nuclear material in proliferating cells of dysplastic epithelium, acetic acid coagulates these proteins obliterating the color of the stroma and the abnormal areas appear as aceto-white areas(13). The sites and characteristics of the lesions were mapped . All women then underwent colposcopy on the same day and if a colposcopically suspected or abnormal lesions was identified punch biopsies were masked with respect to the screening results.The histopathological diagnosis was used as gold standard for women whome biopsies were taken.Results were complied and analyzed .Sensetivity , specificity ,positive predictive value and negative predictive value were then  calculated for PAP smear ,visual inspection with acetic acid, colposcopy or colposcopy with histopathology results as the gold standerd .The statistical test used was the Chi-square test and results were computed using statistical package for social sciences (SPSS) version 12.
RESULTS 
200 women were included in this study. The mean age of the subjects was 36.2 , the mean of parity was 1.6 (table 1) .The most common presenting symptom was vaginal discharge (80%) (table 2) and the most common finding on speculum examination was chronic cervicitis (38%)(table 3 ).Pap smear was recorded as normal or inflammation in 192 (96%) and abnormal in 8 (4%) .these 8 abnormal smears included 5 LSIL, 2 HSIL and one with cells suspicious of malignancy (table 4) .VIA reported positive in 24 subjects (12%) and 88% were VIA negative .Colposcopy was done in all 200 patients and scored to Reid's colposcopic index . A scor of 3-8 was considered positive with regard to dysplasia (table 5 ). Colposcopy was recorded abnormal in 35 cases (17.5) .18 cases (51.4%) had a Reid score of 0-2 and considered negative .17 cases (48.6%) had a positive colposcopy (Reid score 3-8). Cervical biopsy was done on all 35 cases.  44% biopsies were positive and 56% were negative .15 positive biopsies incorporated 11 mild dysplasia,2 moderate dysplasia,1 sever dysplasia and one carcinoma in situ (table 6). Table 7 showed the sensitivity ,specificity, positive predictive value and negative predictive value of both VIA and Pap smear. Inspite of the sensitivity of VIA was 90% more better than of Pap smear which was 50.1%,The specificity of VIA was 37% lesser than that of Pap smear which was 93.2% . 
Table (1)Demographic citeria of the patients 
RANGE (20-50)   mean   36.2+-10.3 YEARSAGE OF THE SUBJECTS           RANGE ( 0-7)   mean 2.61+_1.4PARITY OF THE SUBJECTS      Table (2):Complaints of patients (%) 
Percentages (% )Complaints of patients80%Vaginal discharge                      4%Lower abdominal pain               5%Back ack                             4%Pruritis vulvae                     3%Postcoital  bleeding           3%Dyspareunnia                      1%Intermenstrual bleeding      Table (3):Findings by speculum examination (%)

Percentage  (%)Findings by speculum examination30%                                                Look like normal                 32%                                                   Cervical erosion                  38%                                                 Chronic cervicitis               Table (4)  Pap smear reading (%)                                                                                                                                    
Percentage (%)NumberPap smear reading96%             192                       Normal or inflammatory   4%              8                        Abnormal smear       2.5%
1%             5
2                        LSIL

HSIL 0.5 %       1                     Smear with atypical cellsTable  (5 ) VIA results  (%)
PercentageNumberVIA results12 %24Positive88%176Negative Table  (6):  Colposcopy findings (%)                                                                                                  
Percentage (%)NumberColposcopy findings82.5 %             165               Negative               17.5 %                  35                 Positive               51.4%                     18                 Reid score  (0-2)48.6%                  17                 Reid score  (3-8)Table  (7):  Sensitivity ,specificity , positive predictive value ,Negative predictive value of Pap test,VIAand Colposcopy.                                                                                                  
ColposcopyVIAPap testResult77%90%50.1%Sensitivity       70%37%93.1%Specificity       68%52%89.3%+Ve predictive value
75%81%65.6%-Ve predictive value     

DISCUSSION
Cervical cancer is the leading cause of morbidity and mortality among women worldwide. There are over 500,000 cases of cervical cancer found worldwide, and more than 280,000 women die of it every year. 85% live in developing countries. Cervical cancer is the leading cause of years-of-life lost in women in South Central Asia, Latin America and Sub-saharan Africa, resulting in a greater reduction in a women�s life expectancy even when compared with AID�s, TB, or maternal conditions in Latin America and Europe. (Yang, International Journal of Cancer 2004). The incidence and mortality rates of cervical cancer have declined over 80% in developed countries since the advent of successful screening .The appropriateness of a screening test depends not only on its accuracy ,as measured mainly by sensitivity and specificity but also on its simplicity and safety(5).
Alternative methods for cervical cancer screening have been sought. One method, direct visualization with acetic acid has gained popularity and proven itself in many clinical trials as an adequate alternative to PAP smears in developing countries. In visual inspection with acetic acid (VIA), 5% acetic acid is applied to the cervix with a large cotton swab and left for 30-60 seconds, after which the cervix is visually examined with the naked eye and a lamp. Pre-cancerous lesions, with a higher ratio of intracellular proteins, turn white when combined with acetic acid. Normal cervices without any precancerous lesions, do not change color. This is the same method used when physicians to colposcopy; using the change in color from acetic acid to guide biopsy.
VIA is an attractive alternative to PAP smears for its ease of use, low-cost and fewer physician visits. Currently, to do a PAP smear, the doctor requires a speculum, lamp, slide, cytobrush, microscope, pathologist and a 2-week or more follow-up visit. With VIA, any trained nurse or physician able to use a speculum can do the test. Tools needed include a speculum, lamp, cotton swab, and acetic acid (vinegar); there is no pathologist or physician needed. And, if the test is negative, the patient can be told immediately without having to return to the doctor for results. In rural areas where people travel hours for a doctors� visit, a screening method requiring fewer visits will have a much higher success rate. In this study ,the performance of VIA was evaluated in comparison to Pap smear and colposcopy and \or colposcopy �guided biopsy .In this study colposcopwas done for all patients and a biopsy taken if positive findings were present on Pap smear ,VIA ,or, colposcopy. 
Many studies have been done to compare VIA to PAP smears as a screening method for cervical cancer. Most studies compared VIA with PAP, looking at sensitivities and specificities of both, while comparing them to colposcopy with biopsy as the gold standard.
Gaffkin in 2003 programs, there has been no such trend in developing countries. (Miller, Int Journal of Cancer 2000). Screening programs were implemented in developing countries since the early 1980�s, yet have failed to reduce the mortality rates. The WHO in 2002 estimated that only 5% of women in developing countries are screened appropriately. Likely reasons for failure in screening programs include lack of funding, insufficient access in rural areas where most of the population in developing countries reside, lack of awareness/education as to need for screening, and poor follow-up. About 50% of all cancers occur in developing countries, yet only 5% of resources are spent on the fight against cancer worldwide (Kitchener, The Lancet 1999)published a mini- meta-analysis reviewing the data of what had been published about direct visualization with acetic acid from 1982 to 2002. After finding numerous cites on PubMed, she chose 15 studies from which to review. The 15 studies encompassed over 34,000 women from across the world and the specialists performing the tests ranged from nurses to physicians. The range of estimated VIA sensitivity values from these studies was 66-96% and specificity rates from 64% to 98%. In that study, Gaffikin published test qualities of PAP smears ranging from 11-99%. Gaffikin concluded that VIA was comparable to PAP smears in terms of detecting HGSIL�s or cancer. She also went on to say that, although a lower specificity was noted in various publications, the authors nonetheless unanimously concluded that VIA was useful as an adjuvant or alternate to cytology(14)..
In 2001, Bellinson (15) went to rural China and examined 1,997 women considered to be high risk. In this study they compared visual inspection with acetic acid to colposcopy with biopsy. All exams were performed by gynecologist oncologists and their fellows; the person performing the visual inspection was not the same person performing colposcopy and both examiners were blinded to results. The biopsies included directed biopsies if abnormalities seen, one undirected biopsy at 2, 4, 8, or 10 o�clock at the squamocolumnar junction in each normal quadrant, and an ECC. For biopsy proven CIN II or greater, the sensitivity of VIA was found to be 71% and specificity 74%. The PPV of visual inspection in this study was found to be 11% and the NPV 98%. Bellinson concluded that the sensitivity of VIA equaled or exceeded reported rates for conventional cervical cytology and encouraged continued research into the possibility of a see and treat method for cervical cancer screening.
Two years later, a study in the Phillipines was done, a country where there are almost 70,000 cases of cervical cancer, with ~7,000 new cases each year. (Ladines, PGH cancer Institute) Ngelangel compared VIA to two types of PAP smears. 12,992 women between the ages of 25-65 from five different community hospitals throughout the Philippines underwent four different screening exams: visual inspection with acetic acid, magnified visualization with acetic acid (VIAM), spatula + cotton swab PAP smear and cervical brush PAP smear. He based the quality of these four screening tests on colposcopy with biopsy of suspicious lesions as the gold standard. Both nurses and physicians conducted the studies. Sensitivities for the four tests were found to be 37% for VIA, 34.1% for VIAM, 14.3% for spatula PAP, and 19.1% for cervical brush PAP. The specificity rates were 90.7%, 90.7%, 97.5%, and 97.9% respectively. VIA had the highest sensitivity of the four tests. Ngelangel concluded that the acetic acid visualization and VIAM methods are recommended for initial cervical cancer screening in the Phillipines (16).
Ghaemmaghami tested the VIA method of cervical cancer screening in Iran where cervical cancer is the number one cause of cancer related death in women. 1,200 women between the ages of 18 and 70 from Tehran, Iran were screened by VIA and PAP smear. The women with positive findings on one or both tests underwent colposcopy. Both sensitivity and specificity for VIA were found to be higher in this study. The sensitivity of VIA was found to be 74.3% compared with 72% for PAP smear. The specificity of VIA was 94% compared to 90.2% for PAP. Ghaemmaghami concluded that sensitivity and specificity of VIA is high comparable with that of cytology making it a feasible method of screening in countries where access to cytopathology is limited(17) .
In 2003-2004, concurrent studies were performed by the Alliance for Cervical Cancer Prevention, funded by the Bill and Melinda Gates Foundation; across the world, looking at VIA as an alternative to PAP smears for cervical cancer screening. Studies reached India, Africa and Central America; where the majority of the cervical cancer burden lies. Doh examined VIA as a screening method in Cameroon, Africa, where cancer of the breast and cervix contribute to over 45% of gynecological malignancies and is the most common cause of cancer deaths in women (Doh, International Journal of OB/Gyn 1994). All patients underwent VIA and PAP. If any of the two tests were positive, patients underwent colposcopy with biopsy and one out of ten �negative� cervices were biopsied for control. Only acetowhite lesions with at least a border close to the squamo-columnar junction was considered as significant and positive. Lesions with faint borders were considered low grade and those with sharp borders were considered high grade. Negative cervices had no white lesions. 4,813 women were screened. Sensitivity of VIA was 70.4 % vs 47.7% for PAP. VIA specificity was 77.6% vs 94.2% PAP. PPV of VIA was 44% and NPV 91.3%. Doh concluded that, although PAP has slightly better testing qualities, VIA has acceptable test qualities and may in low resource settings be implemented as a large scale screening method (18).
In India, Goel examined 400 women between the ages of 30-34 attending the Gyn outpatient clinic in New Delhi India. The doctors performed PAP cytology, direct visualization with acetic acid, and colposcopy on all 400 women. Goel found VIA to have a sensitivity of 96.7%, much higher than that of a PAP smear, which they found to be a mere 50%. The specificity of VIA, however, was much lower than the PAP smear, 36.4% vs. 97%. Goel found that VIA was a poor test for catching endocervical lesions, missing 2 cases in this study, and the low specificity of VIA would result in high false positive rates. Overall, Goel concluded that VIA with acetic acid is very sensitive for ectocervical lesions; with its low cost and ease of use making it very advantageous for a primary screening method in developing countries. However, it does have a high rate of false positives, which if using the �see and treat method� would lead to over-treatment (19) .
In rural areas of Northeast Brazil, Bomfim did a similar study. 1,154 women underwent PAP smear and VIA concurrently, with colposcopy if one or both screening tests were positive. Exams were conducted by either nurses or physicians. Sensitivity of VIA was found to be 100% vs 18% for PAP smears and specificity was 78% for VIA vs 100% for PAP smears in detecting LGSIL and HGSIL. The positive predicitive value (PPV) of VIA was 15.6% for LGSIL and 2.8% for HGSIL. The negative predictive value (NPV) of VIA was much better and found to be 100% for both. PAP smear NPV was 97% and 99%. Bomfim concluded that VIA could be an excellent screening method for detecting cervical cancer and affirmed that both trained nurses and physicians would be capable of performing VIA assessment (20).
In urban Africa, Nairobi (Kenya), De Vuyst studied VIA comparing it to three other screening methods, including HPV DNA typing. De Vuyst had 653 women undergo four concurrent screening methods: pap smear, visual inspection with acetic acid (VIA), PCR for high risk HPV and cervicography. The gold standard for affirmative diagnosis was colposcopy and/or biopsy. Sensitivity and specificity were 83.3% and 94.6% for Pap smear, 73.3% and 80.0% for VIA, 94.4% and 73.9% for HR HPV PCR, and 72.3% and 93.2% for cervicography. Although pap smear had the highest sensitivity and HPV PCR the highest specificity, the visual inspections showed an accuracy between the two. De Vuyst concluded that in poor resource countries VIA is effective as a primary screening tool (21).
In 2005, after many evidence based articles substantiated VIA as an adequate screening method for cervical cancer, Lawrence went to Guatemala and implemented a pilot study in evaluating VIA with the �see and treat� method. Lawrence looked at the acceptability of cervical screening using direct visual inspection after acetic acid application followed by immediate cryotherapy for CIN among women in rural Guatemala. Lawrence and colleagues offered cervical cancer screening to 1,052 Guatemalan women using VIA. 9.3% of patients deferred screening at all and refused examination. Among the 954 women screened, 13% were found to have findings consistent with CIN I or higher. 99% of the women with positive findings agreed to undergo immediate treatment with cryotherapy. This study shows that the �see-and-treat� method with VIA could be accepted by patients in developing countries. The drawback to this study was that it did not try and confirm the results of VIA by cytology or histology and treated assuming the VIA test was accurate. However, they did note that their rate of 13% abnormalities was comparable to the numbers found in other studies in the region (22).
These studies have shown that VIA is an adequate and acceptable screening method for cervical cancer. Furthermore, in low-resource areas, VIA can be better than PAP smears for its ease of use and low cost. VIA confers a very high NPV, which means that when a test is negative, the women can go home reassured that she is not likely to have a neoplastic cervical lesion; eliminating the need for follow-up visits. However, the low PPV of VIA does present the problem of many false positives, discouraging the see-and-treat method. However, PPV is dependent on incidence and if a see-and-treat method were implemented in a high-risk population with a high incidence of cervical cancer, the qualities of the VIA test may improve.
Nearly ,the results of all the previous studies were accept VIA as an easy alternative screening test for cancer cervix .The results of this current study were compatible with the previous studies as Pap smear had sensitivity 50.1% ,specificity 93.1%, positive predictive value 89.3% , negative predictive value 65.6% and VIA had sensitivity 90 % ,specificity 37 % ,positive predictive value 52% ,negative predictive value 81 %.So ,VIA as compared to Pap smear can be better screening test due to its ease of use and low cost .VIA had high NPV , which means that when a test is negative ,the women can go home reassured that she is not likely to have a neoplastic cervical lesion.  
Conclusion:                                                                                            
Cytology is the standard of screening of cervical cancer ,so no recommendation to replace it by VIA but,, in countries  with low resources like developing countries where cytology based screening programs are not available So,VIA is a promising alternative .The advantages of VIA are: simple,rapid ,easy to administer,does not need much instructions,cost effective and its result is available immediately. If the result is positive ,in the same setting further investigation can be carried out and management can be planned out  .
REFERENCES
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2) Ferlay J, Shin HR, Bray F, Forman D ,Mathers C, Parkin DM. Estimates of worldwidwnburden of cancer in 2008. GLOBOCAN 2008 Int J Cancer.2010;127:2893-2917
3) Denny L, Kuhan L,Pollack A, WainWright H,Wright TC.Evaluation of alternative methods for cervical cancer screening for resource-poor settings Cancer.2000;89:826-33.
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5) Mar Arbyn,Rengaswamy Sankaranarayanan ,Richard Munwongs ,Namory Keita and Amandou Dolo .Pooled analysis of the accuracy of five cervical cancer screening tests assessd in eleven studies in Africa and India .2008 : Int.J.cancer:123,153-160.
6) Sankaranarayan R, Budhuk A, Rajkumar R, Effective screening programmes for cervical cancer in low and middle income developing countries Bull World health Organs 2001 ;79 :954-62.Back to cited text no.2  
7) Khan MA, Raja FY, Ishfaq G, Tahir F ,Subhan F ,Kazi BM, et al.PAP scrrening for precancerous conditions of the cervical cancer .Pak J Med Res 2005 ; 44:111-3 .Back to cited text no.3
8) The international Agency Research  on cancer (IARC) A prpractical manual on visual screening for cervical neoplasia Lyon:IARC Press 2003 .
9) Visual inspection with acetic acid for cervical-cancer screening :test qualities in a primary care setting .university of Zimbabwe /JHPIEGO cervical cancer project .Lancet.1999;353:869-873.
10) Denny L. The prevention of cervical cancer in developing countries. BJOG 2005;112:1204-12.Back to cited text no.7 {PUBMED}
11) Singh KN, More S.Visual inspection of cervix with acetic acid in early diagnosis of cervical interaepithelial neoplasia and early cancer cervix .J Obestet Gynaecol India 2010 ;60:55-60.
12) Methasinee P,Kamol P, Siriwan T,et al.Visual inspection with acetic acid for detection of grade lesion in atypical squamous cells and low grade squamous intraepithelial lesions from cervical Pap smear .J Gynecol oncol.2011;22(3):145-151.
13) Sankaranarayanan R . Wesley RS, a practical manual on visual screening for cervical neoplasia.Leyon :IARC press and World health organization Distribuation and Sales ,2003:pp 1-49
14)Gaffikin, Lynne DrPH. �Performance of Visual Inspection With Acetic Acid for Cervical Cancer Screening: A Qualitative Summary of Evidence to Date�. Obstetrical and Gynecological Survey 2003. Vol 58(8).
15)Bellinson, JL., Pretorius, RG., Zhang, WH. �Cervical Cancer Screening by Simple Visual Inspection After Acetic Acid.� Obstetrics and Gynecology. 2001. 98(3). 441-444.
16) Ngelangel, C.A. �Acetic-acid guided visual inspection vs. cytology-based screening for cervical cancer in the Philippines.� International Journal of Gyn and OB. 2003. 83.
17)Ghaemmaghami, F. �Visual Inspection with acetic acid as a feasible screening test for cervical neoplasia in Iran.� International Journal of Gyn Cancer. 2004. 14.
18)Doh, A.S. �Visual Inspection with acetic acid and cytology as screening methods for cervical lesions in Cameroon.� International Journal of Gyn and OB. 2005. 89.
19) Goel, A., Gandhi, G., Batra, S. �Visual Inspection of the cervix with acetic acid for cervical intraepithelial lesions.� International Journal of Gynecology and Obstetrics 2005. 88, 25-30.
20) Bomfim, S. �Visual Inspection with acetic acid for cervical cancer detection�. International Journal of Gyn and OB. 2005. 88.
21)De Vuyst, H. �Comparison of pap smear, visual inspection with acetic acid, HPV DNA-PCR testing and cervicography.� International Journal of Gyn and OB. 2005. 89.
22) Lawrence, MJ, Wigton, TR, Leonhardt, JG. �Screening for Cervical Neoplasia in an Unselected Rural Guatemalan Population Using Direct Visual Inspection after Acetic Acid Application: A pilot study.� Journal of Lower Genital Tract Disease. 2005. 9(4). 232-235.

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