Cases Of Cervical Intraepithelial Neoplasia Research Articles

Aberrant Expression of the Cell Polarity Regulator aPKCλ/ι is Associated With Disease Progression in Cervical Intraepithelial Neoplasia (CIN): A Possible Marker for Predicting CIN Prognosis.

Atypical protein kinase C λ/ι (aPKCλ/ι) is a regulator of epithelial cellular polarity. It is also overexpressed in several cancers and functions in cell proliferation and invasion. Therefore, we hypothesized that aPKCλ/ι may be involved in development and progression of cervical intraepithelial neoplasia (CIN), the precancerous disease of cervical cancer induced by human papillomavirus. To do this, we investigated the relationship between aPKCλ/ι expression and CIN. aPKCλ/ι expression level and subcellular localization were assessed in 192 CIN biopsy samples and 13 normal epithelial samples using immunohistochemistry. aPKCλ/ι overexpression (normal epithelium, 7.7%; CIN1, 41.7%; CIN2/3, 76.4%) and aPKCλ/ι nuclear localization (normal epithelium, 0.0%; CIN1, 36.9%; CIN2/3, 78.7%) were higher in CIN samples than normal samples (P<0.05), suggesting that CIN grade is related to aPKCλ/ι overexpression and nuclear localization. Then, 140 CIN cases were retrospectively analyzed for 4-yr cumulative disease progression and regression rates using the Cox proportional hazards model. CIN1 cases with aPKCλ/ι overexpression or aPKCλ/ι nuclear localization had a higher progression rate than CIN1 cases with normal aPKCλ/ι expression levels or cytoplasmic localization (62.5% vs. 9.7% and 63.1% vs. 9.4%, respectively; P<0.001). Multivariate analysis indicated that human papillomavirus types 16 and 18, aPKCλ/ι overexpression (hazard ratio=4.26; 95% confidence interval, 1.50-12.1; P=0.007), and aPKCλ/ι nuclear localization (hazard ratio=3.59; 95% confidence interval, 1.24-10.4; P=0.019) were independent risk factors for CIN1 progression. In conclusion, aPKCλ/ι could be useful for the therapeutic management of patients with CIN, particularly those with non-human papillomavirus 16/18 types.

The expression and clinical significance of Chemerin in cervical intraepithelial neoplasia and cervical cancer

Objective To investigate the expression of Chemerin in cervical intraepithelial neoplasia(CIN) and cervical cancer and its relation with clinicopathological characteristics. Methods The expression of Chemerin was determined with enzyme-linked immunosorbent assay (ELISA) in 35 cervical cancer cases, 20 cervical intraepithelial neoplasia cases and 20 normal persons. The association of serum level of Chemerin with clinicopathological charactersistics was analyzed. Results The level of Chemerin was the highest in cervical cancer cases [(2113.35±198.64)ng/L], higher in CIN [(1562.78±158.65)ng/L], and low in normal persons [(946.36±113.57)ng/L], showing significant difference among three groups. The serum level of Chemerin in cervical cancer were positively correlated with Federation International of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis (P<0.05). Serum Chemerin levels were increased with clinical FIGO stage and showed significantly positive correlation with FIGO stage (rs=0.92, P=0.000). Conclusions The expression of Chemerin in patients with cervical carcinoma is increased. Chemerin may be used as reference indicator to predict its progression in cervical carcinoma. Key words: Adipokines/ME; Cervical intraepithelial neoplasia/ME; Uterine cervical neoplasms/ME

陇南市88590例农村妇女宫颈癌筛查分析与干预

Objective : To understand cervical cancer incidence and risk factors among rural women in Longnan Mountainous Area through screening, and to explore the feasible method and control measures of rural mass screening for cervical cancer. Methods: The 88590 rural women had cervical cancer screening with routine gynecological check, vaginal smear microscopy/cervical secretions smear gram staining microscopy, cervical exfoliated cells, colposcopy examination, histopathological examination, diagnosis, and the test results were retrospectively analyzed. Results: A total of 40756 cases was detected to have genital tract HPV infection, prevalence of 46.01%, 389 cases of cervical intraepithelial neoplasia (CIN), the prevalence was 0.44%, 147 cases of cervical cancer, the prevalence was 0.17%. Conclusion: Cervical cancer screening is an important method for early detection of cervical lesion (CIN) and cervical cancer, which should intensify popularization, expand the scope of screening. Genital tract HPV infection is the most important factor in cervical cancer incidence. We should advocacy prevention and control knowledge. To strengthen health education and to promote rural women's consciousness to participate in the cervical cancer screening, effectively reduce women cervical cancer incidence, raise the level of the health of women.

Expression of adhesion molecule epithelial cadherin and matrix metalloproteinase-9 in squamous neoplasia of the uterine cervix

Background: The objective of the study was to evaluate the expression of cell adhesion molecules [epithelial cadherin (E-cadherin)] and extracellular matrix protease [matrix metalloproteinase (MMP)-9] in preinvasive and invasive lesions of squamous neoplasia of the uterine cervix.Method: The study included 14 cases of cervical intraepithelial neoplasia (CIN) and 43 cases of squamous cell carcinoma (SCC). Immunohistochemistry (IHC) testing was performed for E-cadherin and MMP-9 using the polymer technique. The pathological prognostic parameters, like tumour grade, stage, lymphovascular space invasion and mitosis were compared with the expression of these markers.Results: The mean age of the patients with CIN was 40.1 years, and 50.9 years for those with SCC. Complete uniform membranous expression of E-caherin was demonstrated in the normal epithelium and most CIN (79%). MMP-9 was not expressed in the normal epithelium, whereas 43% of CIN (of which 67% were CIN grade III) were positive. Loss of membranous E...

Evaluation of p16INK4a/Ki-67 Dual Immunostaining in Liquid-based Cytology for Diagnosis of Uterine Cervical Dysplasia and Cancer

Recently, p16INK4a/Ki-67 dual immunostaining has been introduced as a new biomarker protocol for early detection of uterine cervical dysplasia and cancer in liquid-based cytology (LBC). We performed the p16INK4a/Ki-67 dual immunostaining using a CINtec® PLUS kit in a total of 109 LBC cases of cervicovaginal smear and compared its results with those from LBC, HPV hybrid capture II (HC II) test and histological diagnosis. Expression of p16INK4a and Ki-67 was significantly associated with cases of LSIL or higher in cytological diagnosis and cases of cervical intraepithelial neoplasia (CIN) 1 or higher in histological diagnosis (p<0.001 and p<0.001, respectively). Among forty-six cases of atypical squamous cells of undetermined significance (ASCUS) in LBC, p16INK4a and Ki-67 was expressed in 31 (67.4%), which were positively associated with cases of CIN I lesion or higher in histology. The sensitivity of p16INK4a/Ki-67 dual immunostaining for finding lesions of CIN 1 or higher was 89.0%, which was higher than LBC. The specificity was 73.5%, which was higher than that of the HC II test. Based on these results, the p16INK4a/Ki-67 dual immunostaining method can be a useful diagnostic marker for improving the sensitivity of LBC and the specificity of HC II test.

Correlation of Twist and YB-1 up-regulation and epithelial-mesenchymal transition during tumorigenesis and progression of cervical carcinoma

To investigate the clinicopathological significance of Twist and YB-1 up-regulation in cervical cancer, and to correlate the expression of the two genes with E-cadherin, a marker of epithelial-mesenchymal transition (EMT). A total of 202 tissue samples were collected during January 2008 to December 2013, including 50 cases of normal cervical tissues, 100 cases of cervical intraepithelial neoplasia (CIN) and 52 cases of squamous cell carcinoma (SCC). Twist, YB-1 and E-cadherin expression was investigated by MaxVision. Increased expression levels of Twist and YB-1 were found and correlated with the malignant transformation of cervical epithelium, histological progression and metastasis of cervical cancer. In addition, Twist and YB-1 overexpression was also associated with aberrant expression of E-cadherin. Regression analysis revealed that Twist expression was an independent factor for the histological progression of cervical cancer. It is suggested that Twist and YB-1 overexpression is significantly linked to cervical cancer tumorigenesis and progression, likely related to EMT through (YB-1)-Twist-(E-cadherin) pathway. Twist and YB-1 may be markers for determining the metastatic potential of cervical cancer.

NIC: Colposcopia y biopsia dirigida en el diagnóstico de lesiones iniciales del cuello uterino

OBJETIVOS. Difundir el uso del colposcopio y sus indicaciones en la consulta ginecológica, su utilidad frente a un frotis anormal y en el diagnóstico precoz de la neoplasia intraepitelial cervical (NIC) y cáncer preclínico. DISEÑO. Trabajo prospectivo en 247 casos de NIC. LUGAR. Hospital A. Loayza. RESULTADOS. NIC 1 se presentó en 72 casos, NIC II en 73 y NIC III en 102. La mayor incidencia, 30-34 años con 19,1%, despuis 25-29 con 14,6% y de 35-39 con 13,8%. Con respecto a la historia sexual y NIC, el 72% inició su vida sexual antes de los 20 años y tuvo 2 ó más compañeros sexuales el 36,8%. A medida que se incrementa la patología, el diagnóstico se bace más evidente y NIC III alcanza una correlación colposcóspica histológica de 94%. CONCLUSIONES. El NIC se encuentra en edades tempranas. Se hace necesario que toda citología positiva se acompañe de biopsia dirigida. La colposcopia, juntamente con la citología y la biopsia, diagnostica con alta eficacia las lesiones iniciales del cuello uterino y conduce al tratamiento con rapidez.

Significance of TSLC1 gene methylation and TSLC1 protein expression in the progression of cervical lesions

To study the expression and significance of tumor suppressor in lung cancer 1 (TSLC1) gene methylation, the expression of TSLC1 protein in cervix cancer and precancerous lesions as well as their relationship with HR-HPV DNA infection. The clinicopathological data of 92 cases of different cervical lesions during March 2011 to August 2012 treated in our hospital were collected. There were pathologically confirmed 10 cases of normal cervix, 26 cases of cervical intraepithelial neoplasia (CIN) I, 20 cases of CIN II, 15 cases of CIN III, and 21 cases of cervical cancer. Methylation-specific polymerase chain reaction (MSP) was used to detect the TSLC1 gene methylation status in cervical lesions, immunohistochemistry (SP) was used to detect the expressions of TSLC1 protein in cervical lesions, and the second generation hybrid capture (HC2) method was used to detect the high-risk HPV in cervical lesions. The expression rate of TSLC1 gene methylation in normal cervical tissue, CIN I, CIN II, CIN III and SCC were 10.0%, 30.8%, 55.0%, 60.0%, 66.7%, respectively, showing a statistically significant difference (P = 0.004). The positive expression rate of TSLC1 protein in normal cervical tissue, CIN I, CIN II, CIN III and SCC were 100.0%, 80.8%, 65.0%, 33.3%, and 23.8%, respectively, with a significant difference (P = 0.004). In the progression from CIN to invasive cervical cancer, there was no significant correlation between TSLC1 gene methylation and HR-HPV DNA infection (P = 0.919), TSLC1 protein expression and HR-HPV DNA infection (P = 0.664). The correlation analysis showed a negative correlation between TSLC1 gene methylation and TSLC1 protein expression (r = -0.674, P < 0.001). TSLC1 gene promoter methylation may be an early event in the cervical carcinogenesis, become an early sensitive marker, and serve the early prevention and prognostic prediction for cervical cancer.

Clinical effectiveness of VIA and colposcopy based management of cervical intraepithelial neoplasia

Cervical cancer develops from early precancerous lesion known as cervical intraepithelial neoplasia (CIN). Khulna Medical college Hospital provides primary screening for preventing cervical cancer and a secondary referral centre for management of CIN by colposcopy. Primary objective of this study was to do an audit between January 2012 to February 2014 to update clinical efficacy of colposcopy based diagnosis, treatment and follow up of 510 CIN cases and also to document any shortcomings in existing services and suggestion for early rectification. Colposcopic findings in our study group were: 309(60.6%) cases were CIN-1, 124 (24.3%) cases was CIN II, and 49 (9.6%) cases were CIN III. Suspicious of invasive lesion was in 7 (1.4%) abnormal looking cervix and biopsy was done in 21(4.1%). Treatment procedure was done with individualization of cases and options were cold coagulation, Loop electrosurgical excision procedure (LEEP), hysterectomy, biopsy and post treatment follow up. Histopathological diagnosis was documented in 387 cases, where CINI was found in 161 (31.6%), CIN II in 92 (18%), CIN III in 26 (5.1%), non specific Inflammatory cervicitis in 87(17.1%), Squamous cell carcinoma in 15(2.9%), abnormalities consistent with koilocytic atypia in 6 (12%) and reports missed in 123 (24.1%). Cases results showed Positive predictive value (PPV) of 53% and 68% respectively for low grade (CIN I) and high grade lesion (CIN II, III). 481 patient were eligible for post treatment follow up but only 99 (20.5%) patient came and among them 74 (74.7%) were colposcopically negative, 25 (25.2%) had residual CIN and Risk Ratio (RR) was 0.25. Colposcopy is gold standard for diagnosis of CIN but our screening program is opportunistic and far way from population based. Histopathological correlation were often inaccurate with colposcopic diagnosis in practice and about one third case reports were missed. Majority of women did not complete follow up protocol. Residual or recurrent CIN lesion in dropped out cases would be a concern in near future. DOI: http://dx.doi.org/10.3329/bmjk.v47i1-2.22557 Bang Med J (Khulna) 2014; 47 : 16-20

HER-2/neu expression in cervical intraepithelial neoplasia and cervical carcinoma

Objectives: 1) To study the expression of HER-2 in Cervical Intraepithelial Neoplasia (CIN) and Cervical carcinoma 2) To correlate expression of HER-2 with histological type, grade and stage of tumor. Methods: A total of 34 cases were collected during the period from October 2012 to June 2014. Clinical data was collected from medical records. The histopathology slides were analyzed and immunohistochemical (IHC) studies were done on suitable blocks with marker HER-2. Results: Thirty four specimens including 20 cases of squamous cell carcinoma (58.83%), 4 cases of adenocarcinoma (11.76%) and 10 cases of CIN (29.41%) were analyzed. HER-2 expression was noted in 7 out of 10 cases (70%) of CIN. Out of 12 poorly differentiated squamous carcinomas, 8 showed 3+ positivity and 4 showed 2+ positivity. Amongst the 5 moderately differentiated squamous carcinomas, 3 showed 3+ positivity, 1 showed 2+ positivity and 1 case showed 1+ positivity. Amongst the 3 well differentiated squamous carcinomas, 1 showed 1+ positivity and the remaining 2 showed 2+ positivity. Out of the 4 adenocarcinoma cases, 2 moderately differentiated carcinomas showed 3+ positivity and the remaining 2 well differentiated carcinomas showed 2+ positivity. All FIGO stage 4 cases showed 3+ positivity. Stronger HER-2 expression was also noted among cervical carcinoma cases with lymph node and parametrial involvement. Conclusions: The intensity of HER-2 expression increased progressively as grade of lesion increased and with presence of lymph node and parametrial involvement. All the cases under FIGO stage 4 showed strong (3+) HER-2 expression.

Type-specific persistence or regression of human papillomavirus genotypes in women with cervical intraepithelial neoplasia 1: A prospective cohort study.

ObjectiveTo evaluate the type-specific human papillomavirus (HPV) persistence or regression in women with or less than low-grade cervical intraepithelial neoplasia (CIN).MethodsThis prospective cohort study included patients with or less than cytological low-grade squamous intraepithelial lesion (or histologically CIN 1 when biopsy was performed) combined with HPV infection. The cohort was collected from July 2006 to November 2011 at Korea University Guro Hospital. Follow-up was performed with liquid-based Papanicolaou test, hybrid capture 2 test, AnyplexTM II HPV 28 Detection, colposcopic biopsy if necessary every 4 months. All patients were prospectively observed without treatment.ResultsOne hundred and thirty-seven patients were enrolled. Of these, 21 patients whose minimum follow-up periods were less than 8 months were excluded. Finally, one hundred sixteen patients were included and followed-up. Median follow-up period was 16 months. In case of high-risk HPVs, HPV 53 was the most prevalent type, followed by HPV 52, 68, 66, and 16. HPV 16 took 10.6 months to regress spontaneously, which was the longest period among the 10 most prevalent high-risk HPV genotypes. In case of spontaneous regression, HPV clearance was always accompanied by lesion clearance. A total of 13 patients showed disease progression either cytologically or histologically. Two cases of CIN 3 were confirmed by colposcopy-directed biopsy during follow-up, which were subsequently managed by conization.ConclusionHPV 16 is the most persistent HPV genotypes. Studies with longer term follow-up and larger sample size are needed to demonstrate whether persistence of HPV 16 is directly correlated with progression of low-grade lesions.

Management of Cervical Intra Epithelial Neoplasia by Loop Electrosurgical Excision Procedure in a Low Resource Country: An Experience from the Yaound&amp;#233; General Hospital, Cameroon

Background: Cervical cancer is the third most common cancer worldwide, and 80% of cases occur in the developing world. A critical component of effective cervical cancer screening programs is the ability to offer women appropriate and effective treatment for cervical intra epithelial neoplasia (CIN). Objectives: This study aimed at assessing the primary experience of management of CIN by Loop Electrosurgical Excision Procedure (LEEP) in a low resource country. Methods: We carried out a descriptive cross sectional study at the Yaoundé General Hospital in Cameroon. Results: Twenty three cases of CIN were treated by LEEP. Mean age of patients was 40.5 ± 9.9 years. Six (26.1%) patients were infected by the Human Immunodeficiency Virus (HIV). LEEP was indicated in 21 (91.30%) cases for CIN2 and CIN3. The mean duration of the surgical procedure was 10 ± 3 minutes. There was one (4.3%) complication (persistent cervical bleeding). Surgical margins were negative for dysplasia or invasive carcinoma in 18 (78.26%) cases and non-applicable in 5 (21.73%) cases (thermal artefacts of margins and cervicitis without CIN). One patient with micro invasive carcinoma on post-operative histology was treated by total hysterectomy. Cervical cytology was normal at 6 months post LEEP for 15 cases out of 16 (93.8%) patients who performed the test. One woman achieved pregnancy and delivered a term baby. Conclusion: Treatment of CIN by LEEP is feasible, safe and effective in our setting.

Visual inspection techniques versus Pap smear in screening for premalignant and malignant lesions of the cervix in Menoufia governorate, Egypt

Objective The aim of this study was to compare the effectiveness of Pap smear, visual inspection with acetic acid (VIA), and visual inspection with Lugol's iodine (VILI) for mass screening of premalignant and malignant lesions of the cervix in Menoufia governorate in Egypt. Patients and methods This cross-sectional study included a total of 820 women between 30 and 60 years of age who underwent Pap smear, followed by VIA, VILI, colposcopy, and biopsy for confirmation of lesion, if needed. Data were obtained and statistically analyzed. Results The Pap smear was abnormal in 30 (3.6%) women, VIA was abnormal in 70 (8.6%) women, and VILI was abnormal in 74 (9.1%) women. Colposcopic findings were abnormal in 38 (4.6%) women. Cytology missed 25 cases of cervical intraepithelial neoplasia (CIN) (16 CIN-1, eight CIN-2, and one CIN-3) and one case of invasive disease; VIA missed three CIN-1 case and one CIN-2 case; and VILI missed only two cases of CIN-1. The sensitivity, specificity, negative and positive predictive values, and accuracy were as follows: 32, 98, 40, 97, and 95% for Pap smear; 89, 95, 49, 99, and 95% for VIA; and 95, 95, 49, 100, and 95% for VILI, respectively. Conclusion Visual inspection techniques (VIA and VILI) can be used as an efficient primary screening tool instead of Pap smear in low-resource settings.

Conventional cytology, visual tests and evaluation of P16(INK4A) as a biomarker in cervical intraepithelial neoplasia.

(1) To detect cervical intraepithelial neoplasia (CIN) using Papanicolaou test (PAP test), visual tests (visual inspection after the application of acetic acid [VIA], visual inspection after the application of Lugol's iodine [VILI]), colposcopy, and biopsy. (2) To study the biomarker p16(INK4A) expression by immunostaining. Experimental study was conducted from November 2009 to April 2011. 1500 women were screened for cancer cervix using conventional PAP test, VIA, and VILI. Sensitivity, specificity, positive, and negative predictive values of these tests were calculated individually, sequentially, and in parallel. Women having positive results underwent colposcopy and biopsy if required. p16(INK4A) expression in biopsy samples was studied using immunohistochemistry. All test positive cases (n = 235) underwent colposcopy. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PAP with atypical squamous cells of undetermined significance (ASCUS) as cut-off was 40%, 99.25%, 35.25%, and 99.39%; VIA was 60%, 93.06%, 8.03%, and 99.56% and VILI was 80%, 86.06%, 5.4%, and 99.76%, respectively. When PAP, VIA, and VILI were used in parallel sensitivity, specificity, PPV, and NPV improved to 100%, 85.18%, 6.38%, and 100%, respectively. Colposcopic abnormalities were detected in 83 and biopsy proven CIN in 15. p(16INK4A) expression was seen in eight of 15 CIN cases. (1) PAP test and visual techniques are complementary. (2) p(16INK4A) expression was seen in majority of CIN 2 lesions suggesting a higher grade lesion.

Greater expression of the human leukocyte antigen-G (HLA-G) and interleukin-17 (IL-17) in cervical intraepithelial neoplasia: analytical cross-sectional study.

Impaired local cell immunity seems to contribute towards the pathogenesis and progression of cervical intraepithelial neoplasia (CIN), but the underlying molecular mechanisms promoting its progression remain unclear. Identification of new molecular markers for prognosis and diagnosis of early-stage CIN may aid in decreasing the numbers of CIN cases. Several novel immunoregulatory molecules have been discovered over the past few years, including the human leukocyte antigen G (HLA-G), which through interaction with its receptors exerts important tolerogenic functions. Several lines of evidence suggest that T-helper interleukin-17 (IL-17)-producing cells (Th17 cells) may play a role in antitumor immunity. However, recent reports have implicated Th17 cells and their cytokines in both pro and anti-tumorigenic processes. The aim of the study was to evaluate the roles of HLA-G and Th17 in the immunopathogenesis of CIN I. Analytical cross-sectional study with a control group using 58 cervical specimens from the files of a public university hospital providing tertiary-level care. We examined HLA-G and IL-17 expression in the cervical microenvironment by means of immunohistochemistry, and correlated these findings with clinical and pathological features. There was a greater tendency towards HLA-G and IL-17 expression in specimens that showed CIN I, thus suggesting that these molecules have a contribution towards cervical progression. These findings suggest that HLA-G and IL-17 expression may be an early marker for assessing the progression of cervical lesions.

The use of MYBL2 as a novel candidate biomarker of cervical cancer.

Cervical cancer is the third most common cancer affecting women worldwide. It is characterized by chromosomal aberrations and alteration in the expression levels of many cell cycle regulatory proteins, driven primarily by transforming human papillomavirus (HPV) infection. MYBL2 is a member of the MYB proto-oncogene family that encodes DNA binding proteins. These proteins are involved in cell proliferation and control of cellular differentiation. We have previously demonstrated the utility of MYBL2 as a putative biomarker for cervical pre-cancer and cancer. In this chapter we describe the methodological approach for testing MYBL2 protein expression in tissue biopsies from cases of cervical intraepithelial neoplasia (CIN) and cervical cancer, using immunohistochemistry techniques on the automated immunostaining platform, the Ventana BenchMark LT. The protocol outlines the various steps in the procedure from cutting tissue sections, antibody optimization, antigen retrieval, immunostaining, and histological review.

Vaginal hysterectomy for uterovaginal prolapse: what is the incidence of concurrent gynecological malignancy?

Vaginal hysterectomy (VH) is a commonly performed procedure for the operative treatment of uterovaginal prolapse (UVP). The reported incidence of unexpected gynecological cancer in cases of VH for UVP ranges between 0.3 and 0.8 %. Aim of the study is to assess the incidence of malignant and premalignant gynecological histopathological findings among women who underwent a VH for UVP and had a normal preoperative workup. The histopathology reports of women who underwent VH for the treatment of UVP were retrospectively assessed. All women had a history of normal cervical smear tests and a normal preoperative transvaginal scan. Patients with a history of a premalignant or malignant gynecological pathological condition and women with abnormal uterine bleeding were excluded. Overall, 14 out of 333 women who underwent VH (4.2 %) were found to have abnormal histopathological findings of the uterus. Among them, there were 9 cases of endometrial hyperplasia of any type (2.7 %), 1 case of cervical cancer (0.3 %), 1 case of cervical intraepithelial neoplasia (CIN) III (0.3 %), and 3 cases of CINI (0.9 %). No cases of endometrial cancer were detected. Among women who underwent salpingo-oophorectomy (n = 86) three simple serous cysts (3.5 %) were found, with no cases of ovarian cancer. The incidence of unexpected premalignant or malignant gynecological pathological conditions among asymptomatic women who underwent VH, with a history of normal cervical smear tests and normal preoperative TVS, was low but not negligible. This information should be included in the preoperative counseling of women planning to undergo surgery for UVP.

MEKK3 and survivin expression in cervical cancer: association with clinicopathological factors and prognosis.

Mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3 (MEKK3) is an important protein kinase and a member of the MAPK family, which regulates cellular responses to environmental stress and serves as key integration points along the signal transduction cascade that not only link diverse extracellular stimuli to subsequent signaling molecules but also amplify the initiating signals to ultimately activate effector molecules and induce cell proliferation, differentiation and survival. To explore the relationship between MEKK3 and cell apoptosis, clinicopathology and prognosis, we characterize the expression of MEKK3 and survivin in cervical cancer. MEKK3 and survivin expression was measured by RT-PCR and Western blotting of fresh surgical resections from 30 cases of cervical cancer and 25 cases of chronic cervicitis. Protein expression was detected by tissue microarray and immunochemistry (En Vision) in 107 cases of cervical cancer, 86 cases of cervical intraepithelial neoplasia (CIN), and 35 cases of chronic cervicitis. Expression patterns were analyzed for their association with clinicopathological factors and prognosis in cervical cancer. Expression of MEKK3 and survivin mRNA was significantly higher in cervical cancer than in the controls (p<0.05). MEKK3 and survivin expression differed significantly between cervical carcinoma, CIN, and cervicitis (p<0.05) and correlated with clinical stage, infiltration depth, and lymph node metastasis (p<0.05). MEKK3 expression was positively correlated with survivin (p<0.05). Kaplan-Meier survival analysis showed that MEKK3 and survivin expression, lymph node metastasis, depth of invasion, and FIGO stage reduce cumulative survival. Cox multivariate regression analysis showed that MEKK3, survivin, and clinical staging are independent prognostic factors in cervical cancer (p<0.05). Expression of MEKK3 and survivin are significantly increased in cervical cancer, their overexpression participating in the occurrence and development of cervical cancer, with protein expression and clinical staging acting as independent prognostic factors for patients with cervical cancer.

A retrospective analysis of the clinical performance of human papillomavirus testing using SurePath sample collection

We present a retrospective analysis of our high-risk human papillomavirus (hr-HPV) test performance using SurePath samples, and we compare these results to published results from Kaiser Permanente of Northern California, where hr-HPV testing was performed using collection in standard transport medium. We retrospectively identified histopathologic cases of cervical intraepithelial neoplasia (CIN) 2+ from 2010 through 2012, as well as all hr-HPV results performed from SurePath samples in these women. Testing for hr-HPV in our laboratory consisted of either Hybrid-Capture 2 or Cervista. These results were used to calculate false negative rates for CIN 2+, CIN 3+, and carcinoma, for both test methods, and these rates are compared with those published by Kaiser Permanente of Northern California. The false negative rate for hr-HPV testing from SurePath samples (combined Hybrid-Capture 2 and Cervista) at the histopathologic level of CIN2+ was 7.9% (95% confidence interval: 5.9-10.2). This is compared with the false negative rates from collection in standard transport medium reported by Kaiser Permanente of Northern California for CIN 2+ of 20.4% (95% confidence interval: 18.9-22.0). Similar calculations for CIN 3+ and carcinoma are presented, along with comparison to the Kaiser Permanente of Northern California results. With regard to false negative hr-HPV results, for all levels of histopathologic abnormality, our hr-HPV testing from SurePath samples showed either significantly better performance (for CIN 2+ regardless of method, CIN 3+ using Cervista), or equivalent performance (for CIN 3+ using Hybrid-Capture 2 and carcinoma regardless of method). Our retrospective analysis demonstrates that hr-HPV testing from SurePath samples meets the proposed sensitivity of ≥90% in cases of biopsy proven CIN 2+.

Correlation between Colposcopy and Histopathologic Diagnosis from Colposcopy-Guided Biopsies

Cervical cancer is preventable and curable when detected in its early stages. Colposcopy with biopsy is used in the evaluation and management of patients with cervical lesions. The aims of this study are to correlate the colposcopic diagnosis to the actual histopathologic diagnosis, and to determine the accuracy, sensitivity and specificity of acetowhitening in distinguishing premalignant and malignant lesions of the cervix. Review of slides and patient charts were done on 121 patients who underwent colposcopy with biopsy at the Outpatient department (OPD) of the Philippine General Hospital (PGH). Statistical analysis was done using chi square approximation. Histologic results revealed that there were four malignant or suspicious for malignancy cases, 3 cases of cervical intraepithelial neoplasia 3 and 96 benign cases. The accuracy of colposcopy was found to be 43% (95% CI: 34-54%). The sensitivity of acetowhitening was 71% (95% CI: 29-96%) while the specificity of acetowhitening was 42% (95% CI: 32-52%). This study showed that colposcopy is a good screening tool in detecting high-grade lesions but must be used with caution because of its low specificity. Low specificity of colposcopy in the OPD may be attributed to the varying levels of expertise of the colposcopists.  Keywords: pathology, cervical cancer, colposcopy