Indian Journal of Cancer
Home  ICS  Feedback Subscribe Top cited articles Login 
Users Online :1055
Small font sizeDefault font sizeIncrease font size
Navigate here
Resource links
 »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
 »  Article in PDF (747 KB)
 »  Citation Manager
 »  Access Statistics
 »  Reader Comments
 »  Email Alert *
 »  Add to My List *
* Registration required (free)  

  In this article
 »  Abstract
 » Introduction
 »  Materials and Me...
 » Results
 » Discussion
 »  References
 »  Article Figures
 »  Article Tables

 Article Access Statistics
    PDF Downloaded278    
    Comments [Add]    

Recommend this journal


  Table of Contents  
Year : 2016  |  Volume : 53  |  Issue : 1  |  Page : 67-73

Abnormal uterine cervical cytology in a large tertiary hospital in Bangkok metropolis: Prevalence, management, and outcomes

1 Department of Obstetrics and Gynecology, Faculty of Medicine, Vajira Hospital, University of Bangkok Metropolis, Thailand
2 Department of Obstetrics and Gynecology; Anatomical Pathology, Faculty of Medicine, Vajira Hospital, University of Bangkok Metropolis, Thailand

Date of Web Publication28-Apr-2016

Correspondence Address:
S Tangjitgamol
Department of Obstetrics and Gynecology; Anatomical Pathology, Faculty of Medicine, Vajira Hospital, University of Bangkok Metropolis
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-509X.180827

Rights and Permissions

 » Abstract 

Objectives: To determine the prevalence of abnormal cervical cytology, management, and association with clinical significant histopathology including cervical intraepithelial neoplasia II or adenocarcinoma in situ and more severe lesions. Materials and Methods: Women with abnormal cervical cytology from January 2005 to December 2009 were identified from the archives of Department of Anatomical Pathology and Department of Obstetrics and Gynecology. Demographic data, type of abnormal cytology, management, and their associated histopathology were collected. Results: During the study period: 2533/54,179 women (4.7%) had abnormal cervical Pap test. Squamous lesions were more common than glandular lesions: 2309 (4.3%) compared to 224 (0.4%). Atypical squamous cell (ASC) was most commonly found (1449 or 2.7%), whereas low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intra-epithelial lesion (HSIL), or squamous cell carcinoma (SCC) were found in 648 (1.2%) and 212 (0.4%), respectively. Among abnormal glandular cytology, atypical glandular cell (AGC) was most commonly found (199 women or 0.4%) whereas adenocarcinoma and endometrial cell in woman aged >40 year were found in only 14 (0.02%) and 11 women (0.02%), respectively. Majority (77.3%) underwent further investigations. We found that 13.0% of ASC, 20.3% of LSIL, and 78.7% of HSIL and SCC had clinical significant histopathology. In glandular abnormalities: 14.9% of AGC, 33.3% of women aged >40 years with endometrial cell, and 66.7% of adenocarcinoma were histologically proven to be of clinical significant. Conclusions: ASC was the most common abnormal cervical cytology. Cytology abnormalities of HSIL and SCC had the highest association with clinical significant histopathology.

Keywords: Abnormal cervical cytologic, clinical significant histopathology, management

How to cite this article:
Kingnate C, Tangjitgamol S, Khunnarong J, Manusirivithaya S. Abnormal uterine cervical cytology in a large tertiary hospital in Bangkok metropolis: Prevalence, management, and outcomes. Indian J Cancer 2016;53:67-73

How to cite this URL:
Kingnate C, Tangjitgamol S, Khunnarong J, Manusirivithaya S. Abnormal uterine cervical cytology in a large tertiary hospital in Bangkok metropolis: Prevalence, management, and outcomes. Indian J Cancer [serial online] 2016 [cited 2021 Sep 25];53:67-73. Available from: https://www.indianjcancer.com/text.asp?2016/53/1/67/180827

 » Introduction Top

Cervical cancer is the second most common gynecologic cancer among females worldwide, accounting for 9% of new cancer cases and 8% of cancer deaths in female in 2011,[1] with majority of these new cases and deaths occur in developing countries. In Thailand, cervical cancer is the second most common cancer in female after breast cancer, with the age-standardized incidence rate (ASR) of 18.1 per 100,000 per year, and is also the second most common cause of cancer death after hepatobiliary cancer.[2] One effective means to reduce mortality is early detection and appropriate management of pre-cancerous lesions and early invasive cervical cancer.

Cervical cytology is the most common practice among cervical cancer screening methods due to its accessibility and low cost. Cytologic reports by the Bethesda System [3] group epithelial cellular abnormalities into squamous or glandular cells which are further classified according to the degrees of abnormality. In brief, squamous cell abnormality ranges from atypical squamous cell (ASC) which is further sub-grouped into ASC of undetermined significance (ASC-US) and ASC cannot exclude high-grade lesion (ASC-H), low-grade and high-grade intra-epithelial lesions (LSIL and HSIL), squamous cell carcinoma in situ (CIS), and squamous cell carcinoma (SCC). Glandular cell which has similar range of abnormalities from atypical glandular cell (AGC) to adenocarcinoma in situ (AIS) and adenocarcinoma (ACA), has special connotation regarding its origin of endocervix, endometrium, or not otherwise specified.

Although all abnormal cytology require an attention from a physician, further investigation and management may vary according to the type and degree of cellular abnormalities which carry different risks of underlying histopatholgy.[4] ASC-US is the only cytologic abnormality which has triage options of management of follow-up cytology, HPV DNA testing, or colposcopy whereas ASC-H or AGC or more severe lesions require an investigation which is usually colposcopy. Women with AGC or more severe lesions require several investigations due to various possible sites of origin: Colposcopy with endocervical sampling and with endometrial sampling in women aged ≥35 years or when clinically indicated.[4]

Despite having guidelines for abnormal cervical cytology management, some women or even some physician may not follow the recommendation.[5],[6] A deviation from the practice guidelines may hinder the effectiveness of cervical cancer reduction aside from the sub-optimal coverage of cervical cytologic screening. Awareness of these problems should be there especially in developing countries where cervical cancer is common.

This study aimed to determine the prevalence and distribution of abnormal cervical cytologic results, demographic data, management of women with abnormal  Pap smear More Details, histologic diagnosis from investigation especially clinical significant lesions, and further treatment.

 » Materials and Methods Top

This study was conducted after an approval from the Institution Ethics Committees. Women who had cervical cytology performed in our institution were identified. Inclusion criteria were women with abnormal cervical Pap smear between January 2005 and December 2009. Exclusion criteria were women who had history of pre-invasive or invasive cervical lesions, prior hysterectomy, and incomplete medical record. Women's clinical and pathological data were retrieved from the archives of Departments of Anatomical Pathology and of Obstetrics and Gynecology. Data collected were age, marital status, gravidity, parity, menopausal status, use of hormonal contraception, history of sexual transmitted disease including human immunodeficiency virus (HIV) infection, indication of Pap smear, type of abnormal cytology, subsequent investigations, primary histologic diagnoses, further management, definite histopathology, and follow-up data. Definite histopathology was referred to the most severe histologic diagnosis of the woman. We categorized the cytologic abnormalities into two groups: Mild (ASC/LSIL/AGC/endometrial cell in woman >40 years old) or more severe lesions (HSIL/CIS/SCC/ACA) to evaluate their associations with clinical features, and with clinically significant histopathologic lesions. Clinical significant histopathology included cervical intraepithelial neoplasia (CIN) II, CIN III, SCC, AIS, and ACA.

As a general practice in our institution, women with LSIL or more severe lesions are scheduled for colposcopy. Any suspicious lesions will be directly biopsied under colposcope. Endocervical curettage (ECC) is additionally performed in unsatisfactory colposcopy or when there are no gross cervical abnormalities. Women with unsatisfactory colposcopy and have negative ECC, and those who have satisfactory colposcopy with no suspicious lesion are defined as “normal colposcopy” and would simply be followed-up by a Pap smear surveillance. Subsequently, women with cervical histopathologic diagnosis of CIN I would also be periodically followed-up by Pap test whereas women with histopathologic diagnoses of CIN II-III, AIS or inconclusive diagnosis would be scheduled for cervical conization.

Data were analyzed using SPSS statistical software version 11.5 (SPSS, Chicago, IL, USA). Descriptive statistics were used for demographic data and summarized as number of frequency and percentage, mean with standard deviation (SD), or median with range. Differences between variables were evaluated with Chi-square or Fisher's exact test as appropriate. The primary outcome was considered significant only if P < 0.05.

 » Results Top

Among 54,179 women who underwent cervical Pap smear, 2533 (4.7%) had abnormal cytology. Characteristic features of the women are shown in [Table 1]. Squamous cytologic lesions were more common than glandular lesions. ASC or AGC were most commonly found in each category. Details of abnormal cytologic results are shown in [Table 2]. Squamous cytologic lesions are demonstrated in [Figure 1]. Glandular cytologic lesions, including endometrial cells in woman >40 years, are shown in [Figure 2]. We studied clinical features of the women according to the severity of their abnormal cytology and found women aged >50 years or women with reactive anti-HIV status were significantly associated with HSIL or more severe lesions. History of contraception tended to show such association but not statistically significant [Table 3].
Table 1: Clinical characteristic features of women with abnormal cervical cytology (N=2533)

Click here to view
Table 2: Details of abnormal cervical cytology according to squamous or glandular lesions (N=2533)

Click here to view
Figure 1: Squamous lesions. (a) ASC-US: Atypical squamous cell of undetermined significance; (b) ASC-H: Atypical squamous cell cannot exclude high-grade lesion; (c) “Koilocytic” LSIL: Low-grade squamous intraepithelial lesion; (d) “Non-koilocytic” LSIL; (e) HSIL: High-grade squamous intra-epithelial lesion; (f) SCCA: Squamous cell carcinoma

Click here to view
Figure 2: Glandular lesions. (a) Endometrial cell in woman aged > 40 years; (b) AGC: Atypical glandular cell-Atypical endocervical cells; (c) AGC: Atypical endometrial cells; (d) Endometrial ACA: Adenocarcinoma

Click here to view
Table 3: Clinical characteristic features of women according to the severity of abnormal cervical cytology (N=2533)

Click here to view

From 2533 women with cervical cytologic abnormalities, 1959 women were managed in our institution whereas 574 were lost to follow-up. The cytologic abnormalities of women who were lost to follow-up were (in order of frequency) ASC (318 cases; 55.4%), LSIL (184; 32.1%), AGC (37; 6.5%), HSIL (25; 4.4%), CIS/SCC/or ACA (8; 1.4%), and endometrial cells in women aged >40 years (2; 0.3%). We found some common features among these lost-to follow up women: 83.1% were asymptomatic (screening group), 66% aged ≤40 years (median age of 33 years old), and 46.3% had ASC-US.

Among 1959 women who were managed in the institution, 94 women had only follow-up cytology: 56 women with ASC-US (medically scheduled for follow-up) and 38 women with ASC-H or LSIL or AGC or endometrial cell in woman aged >40 years (personal reasons for a delayed follow-up). The majority underwent further investigations comprising direct operative procedure or colposcopy. Median time interval from abnormal Pap smear to colposcopy was 9.3 ± 7.4 weeks (range, 1.0-110.7 weeks). Women with satisfactory colposcopy without any suspicious lesions (189; 10.6%) had no further management whereas the remaining underwent primary operative procedures at colposcopy (1587; 89.4%). Secondary investigations and definitive surgical procedures were then subsequently performed based on the primary or secondary histopathologic results. All primary investigations and subsequent managements for all women with abnormal cytology are detailed in [Table 4].
Table 4: Management of women with abnormal cervical cytology (N=2533)

Click here to view

We studied definite histopathology in association with cytologic abnormalities [Table 5] and found that 13.0% of ASC, 20.3% of LSIL, and 78.7% of HSIL or more severe lesions had clinically significant histopathology. In glandular abnormalities: 14.9% of AGC, 33.3% of women aged >40 years with endometrial cell, and 66.7% of ACA were histologically proven to be of clinical significance.
Table 5: Abnormal cervical cytology according to their histology/histopathology (N=1676)

Click here to view

Regarding follow-up data among 155 women who had definite hysterectomy, 77 women (49.7%) did not have follow-up cytology. Their indications for hysterectomy are as follows: Benign lesions (23 women), pre-invasive cervical lesions (46 women), and malignancy (eight women with cancers of uterus, ovary, rectum, and cervix). Among 78 women who had 1-9 times of follow-up cytology after hysterectomy in a median follow-up period of 20.6 ± 13.0 months (range, 2.6-52.6 months), only 12 (15.4%) had recurrent abnormal cytology of vaginal vault (seven had prior pre-invasive cervical lesions and five had invasive cervical or uterine cancer). The remaining 66 women (84.6%) showed no recurrent abnormal cytology. [Table 6] shows details of follow-up cytology of women who had definite treatment as hysterectomy.
Table 6: Details of follow-up cervical cytology of women who underwent definitive treatment according to the primary cytology results (N=78)

Click here to view

Among 1804 women who had conservative surgery (n = 1710) or follow-up Pap tests (n = 94), 594 women (32.9%) were lost to follow-up [Table 7]. The remaining 1210 women had subsequent up Pap tests for 1-9 times with a median follow-up period of 15.0 + 11.8 months (range: 0.7-65.1 months). Most (946; 78.2%) women had uneventful follow-up findings whereas 264 women (21.8%) had recurrent abnormal cytology as ≥HSIL in 31 women (2.6%) and less severe cytologic lesions in 233 women (19.3%). Only age ≤40 years and reactive HIV status were significantly associated with recurrent abnormal cervical cytology: 24.9% versus 19.4% (P = 0.022) for age and 44.3% versus 22.4% for HIV status (P < 0.001). Severity of the first abnormal Pap result was not a significant factor for recurrence: 20.5% in more severe cytology versus 22.1% in mild cytology (P = 0.630).
Table 7: Details of follow-up cervical cytology of women who underwent conservative treatment according to the primary cytology results (N=1210)

Click here to view

 » Discussion Top

Most previous reports focused on the prevalence of each type of abnormal cervical cytology i.e., ASC, AGC, LSIL or HSIL.[7],[8],[9],[10],[11],[12],[13] Only few reported the prevalence of abnormal cervical cytology altogether.[14],[15],[16] Two previous studies reported 3% or 5% prevalence,[14],[15] which were close to 4.7% in our study. Only one study reported a high prevalence of 15%.[16] Different figures of abnormal cytology in each study may lie on characteristics of the population studied e.g., age, immune status, or indication for cytologic screening, etc., For example, age of the women in one previous study and our study (<% of abnormal cytology) ranged from 15 to 88 years and more than half of them had screening cytology without symptom.[15] This was in contrast to the study with high prevalence (15%) which had population with higher risk features for cervical lesions: All were reproductive age women and 6% were commercially sex workers.[16]

We found squamous more common than glandular lesions. This was consistent with the reality that SCC is the most common histopathology of cervical cancer.[17] Our finding was also consistent with previous reports that ASC or LSIL were more common whereas ≥HSIL or ACA were less common.[14],[15],[16] Some clinical factors should be of concern in managing women with abnormal cytology especially features associating with severe cytologic abnormality. We found that women aged > years or reactive anti-HIV status was significantly associated with HSIL or more severe lesions. In contrast, the history of contraception tended to associate with < HSIL, but was not statistical significant. Other studies found that women aged >35 years or parity ≥1 tended to be associated with HSIL or more severe lesions.[7],[15]

As mentioned earlier, management of abnormal cytology depends mainly on the type and severity of cellular abnormalities.[4] Subsequent investigations and managements depend on many factors such as: Age, colposcopic findings, histopathology, and accordance between cytologic and histopathologic findings. The clinical practice in our institution generally follows the guideline recommended by the American Society of Colposcopy and Cervical Pathology 2006.[4] All women with abnormal cytology will be contacted by phone or postal mail to have further investigations and management. Nevertheless, nearly one-fourth of women who had cytologic abnormalities had no further data in the hospital record. We did not know actual numbers of women who were really lost to follow-up, or sought to have management in the other hospital according to the national reimbursement policy. This is a limitation of any study in the country which does not have a national data registry of pre-invasive or invasive cancers that complete data of a woman is difficult to be obtained.

Among those who had follow-up data, majority underwent colposcopy with a median time of 9 weeks. Among those women who had delayed examination, 62.1% had ASC-US and 23.7% had LSIL. This was due to our institution policy to schedule those with more severe cytologic abnormalities to have colposcopy earlier. This long period of waiting for scheduled colposcopy was a common problem encountered in a tertiary center.[18] Awareness about this problem and proper management would prevent some women who might lose their interest or concern for a further investigation.

At the time of colposcopy, other procedures were performed depending on age, type of abnormal cytology, and colposcopic findings [Table 3]. Excluding 23% who did not have additional data in the institution as described earlier, deviation from a practice guideline was found in 65/1959 women (3.3%): 38 women (58.5%) did not come back for scheduled colposcopy and had follow-up cytology instead whereas 27 women (41.5%) had immediate hysterectomy without a colposcopic examination or tissue histopathology due to other associated gynecologic pathology [Table 3]. The gynecologist may have considered that these women had only mild cytologic abnormalities or had more serious co-incidental pathology to necessitate hysterectomy: Benign tumors with symptoms, or gynecologic malignancies. Fortunately, all of these women did not have severe cervical pathology from final histopathology of hysterectomy. Few previous studies addressed the problem that some women or even physicians did not follow the recommendation for management of abnormal cervical cytology.[5],[6] Common factors of deviation were either the women themselves or the health facilities: Younger age, lower education, mild degree of abnormal cytology, or small size health facilities. We also found factors that may render a loss to follow-up: Having no symptom, younger age, and mild degree of abnormal cytology. One limitation of our finding was that some women might have further treatment elsewhere.

Our study included all types of cytologic abnormalities in our study with an intention to give the overall panoramic image of women with cytologic abnormalities, their management, and outcomes. We found that the significant histopathologic lesions were found in 13% of ASC, 20% of LSIL, and 79% of HSIL or more severe lesions. This was also observed in abnormal glandular cytology: 15% of AGC, 33% of endometrial cell in women aged >40 years, and 67% of ACA. A direct relationship of significant histopathology and the degree of cytologic abnormalities demonstrated in our study were in accordance with other studies which focused on each type of cytologic abnormalities.[7],[8],[9],[10],[11],[12],[13]

Aside from a broad scope of cytologic abnormalities we studied, a longitudinal data were also assessed. Excluding 155 women who had definite surgical procedure of hysterectomy, nearly 22% of women who had conservative management had recurrent abnormal cytology (2.6% of the recurrence was HSIL or more severe lesions). Age ≤40 years and reactive HIV status were significantly associated with recurrent abnormal cervical cytology in our study. This data should be informative for both women and physician that an adequate period of follow-up is required after a conservative management. We do not know if the women really acquired a new lesion or it was a true recurrence from persistent or reactivating HPV infection after the primary conservative treatment. A definitive surgical management may not dispose the requirement of follow-up cytology because 15% of women who had hysterectomy also had recurrent abnormal cytology.

With the results from our study involving all types of cytologic abnormalities from a single institution; we hope that one can better see various pathways of each cytologic category including their clinical managements and long-term outcomes. Not of lesser importance, our missing data from women who were lost to follow-up or referred to have management elsewhere should stimulate the national health sector to set up a registry unit to collect all data and to better manage women with abnormal cervical cytology. This might ultimately decrease number of cervical cancer patients in the country.

 » References Top

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.  Back to cited text no. 1
Khuhaprema T, Srivatanakul P, Sriplung H, Wiangnon S, Sumitsawan Y, Attasara P. Cancer in Thailand 2001-2003. Vol. V. Bangkok: Ministry of Public Health and Ministry of Education; 2010.  Back to cited text no. 2
Solomon D, Davey D, Kurman R, Moriarty A, O'Connor D, Prey M, et al. The 2001 Bethesda System: Terminology for reporting results of cervical cytology. JAMA 2002;287:2114-9.  Back to cited text no. 3
Wright TC Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D, et al. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol 2007;197:346-55.  Back to cited text no. 4
Singhal R, Rubenstein LV, Wang M, Lee ML, Raza A, Holschneider CH. Variations in practice guideline adherence for abnormal cervical cytology in a county healthcare system. J Gen Intern Med 2008;23:575-80.  Back to cited text no. 5
Cheng WF, Chen YL, You SL, Chen CJ, Chen YC, Hsieh CY, et al. Risk of gynaecological malignancies in cytologically atypical glandular cells: Follow-up study of a nationwide screening population. BJOG 2011;118:34-41.  Back to cited text no. 6
Limpvanuspong B, Tangjitgamol S, Manusirivithaya S, Khunnarong J, Thavaramara T, Leelahakorn S. Prevalence of high grade squamous intraepithelial lesions (HSIL) and invasive cervical cancer in patients with atypical squamous cells of undetermined significance (ASCUS) from cervical Pap smears. Southeast Asian J Trop Med Public Health 2008;39:737-44.  Back to cited text no. 7
Khuakoonratt N, Tangjitgamol S, Manusirivithaya S, Khunnarong J, Pataradule K, Thavaramara T, et al. Prevalence of high grade squamous intraepithelial lesion (HSIL) and invasive cervical cancer in patients with low grade squamous intraepithelial lesion (LSIL) at cervical Pap smear. Asian Pac J Cancer Prev 2008;9:253-7.  Back to cited text no. 8
Tavaramara T, Manusirivithaya S, Prutthiphongsit W. Prevalence of atypical glandular cells of undetermined significance (AGUS) from cervical Pap smear. Vajira Med J 2002;46:9-17.  Back to cited text no. 9
Pothisuwan M, Tavaramara T, Manusirivithaya S, Phaloprakarn C, Tangjitkamol S. Prevalence of clinical significant lesions in atypical glandular cell of undetermined significance (AGUS) from cervical Pap smear. Thai J Obstet Gynaecol 2009;17:108-15.  Back to cited text no. 10
Kietpeerakool C, Srisomboon J, Tantipalakorn C, Suprasert P, Khunamornpong S, Nimmanhaeminda K, et al. Underlying pathology of women with “atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion” smears, in a region with a high incidence of cervical cancer. J Obstet Gynaecol Res 2008;34:204-9.  Back to cited text no. 11
ASCUS-LSIL Traige Study (ALTS) Group. A randomized trial on the management of low-grade squamous intraepithelial lesion cytology interpretations. Am J Obstet Gynecol 2003;188:1393-400.  Back to cited text no. 12
Kantathavorn N, Phongnarisorn C, Srisomboon J, Suprasert P, Siriaunkgul S, Khunamornpong S, et al. Northern Thai women with high grade squamous intraepithelial lesion on cervical cytology have high prevalence of underlying invasive carcinoma. Asian Pac J Cancer Prev 2006;7:477-9.  Back to cited text no. 13
Insinga RP, Glass AG, Rush BB. Diagnoses and outcomes in cervical cancer screening: A population-based study. Am J Obstet Gynecol 2004;191:105-13.  Back to cited text no. 14
Chomsevi K, Jatuparisuth N. Abnormal Pap smear of the uterine cervix at BMA general hospital. Vajira Med J 2002;46:97-104.  Back to cited text no. 15
Rugpao S, Koonlertkit S, Ruengkrist T, Lamlertkittikul S, Pinjaroen S, Limtrakul A, et al. ThinPrep Pap-smear and cervical intraepithelial neoplasia in reproductive-aged Thai women. J Obstet Gynaecol Res 2009;35:551-4.  Back to cited text no. 16
Miller C, Elkas JC. Cervical and vaginal cancer. In: Berek JS, editor. Berek and Novak's Gynecology. 15th ed. Philadelphia: Lippincott Williams and Wilkins; 2012. p. 1304-49.  Back to cited text no. 17
Kuo TM, Benard VB, Berkman ND, Martin CK, Richardson LC. Timing of colposcopy after cervical cytologic abnormalities. Obstet Gynecol 2010;115:629-36.  Back to cited text no. 18


  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]


Print this article  Email this article


  Site Map | What's new | Copyright and Disclaimer
  Online since 1st April '07
  © 2007 - Indian Journal of Cancer | Published by Wolters Kluwer - Medknow