Early Detection Of Cervical Carcinoma Research Articles

Cervical cytochemistry: a potential adjunct to cytomorphology for detection of abnormal cells in cervical cancer screening

Background: Pap smear examination has been universally used as an effective screening tool for early detection of cervical carcinoma. The aim of this study was to assess the utility of Cervical Acid Phosphatase staining as an adjunct to routine Pap smear testing to improvethe sensitivity and specificity of routine Pap smear examination for cervical cancer detection.
 Materials and Methods: Cervical smears were taken from patients attending the gynecology department and a few cervical cancer screening programmes. One set of slides were alcohol fixed and stained with rapid pap stain and another set of slides were fixed in a special fixative and stained with Cervical Acid Phosphatase -Pap stain. The nuclear features of these Cervical Acid Phosphatase stained dysplastic cells was studied on Pap stain to diagnose cervical intraepithelial lesion/ malignancy.
 Results: Out of 489 cases included in the study 6 cases were diagnosed with intraepithelial lesion/ malignancy. On Cervical Acid Phosphatase -Pap stain 2 of the cases diagnosed as inflammatory smears on pap stain showed Cervical Acid Phosphatase positivity and thus were re evaluated. Mild nuclear atypia was observed in the Cervical Acid Phosphatase positive cells and these cases were diagnosed as Low grade squamous intraepithelial lesion and later biopsy proven to be Cervical intraepithelial Neoplasia I. Therefore Cervical Acid Phosphatase -Pap test was 100% sensitive and specific for cervical cancer detection.
 Conclusions: With 100% sensitivity Cervical Acid Phosphatase -Pap test satisfies the criteria of an efficient screening test.

Comparative study of Pap smear test and VIA test in cervical carcinoma screening among women aged over 20 years

Objective
 To compare the performance of VIA and Pap smear tests as screening tools in cervical carcinoma detection in women.
 Methods
 The prospective and retrospective study was conducted on 198 women. Cervical smears were collected with Ayres’s spatula. Acetic acid was used and the results were categorized as VIA positive and VIA negative. The Pap smear was reported according to the Bethesda system 2001. Cervical biopsy was done for all the cases.
 Results
 VIA was positive in 47.47% of the cases and Pap smear was positive in 39.89% of the cases. Among 198 cases, 61 (30, 8%) cases had cervical carcinoma. When we compared VIA and Pap smear tests, 94 cases were positive to VIA, and 61cases were confirmed positive with Pap smear. The sensitivity and specificity for VIA were 88.5% and 84.68%, respectively. The sensitivity and specificity for Pap smear were 80.45% and 91.89%, respectively. The sensitivity of VIA was higher than that of Pap smear. However, the specificity of VIA was low as compared to Pap smear.
 Conclusion
 VIA is a cost effective test and could be alternatively used with Pap smear in screening of cervical carcinoma but the Papanicolaou test is the most effective test for early detection of cervical carcinoma.
 Keywords: Pap smear test; VIA test; cervical carcinoma; women

Upregulation of stem cell markers ALDH1A1 and OCT4 as potential biomarkers for the early detection of cervical carcinoma

Previous studies have reported the upregulation of stem cell biomarkers that are associated with tumorigenesis, in particular with cancer infiltration, recurrence and metastasis. Infection by human papilloma virus (HPV) is the main etiopathological factor of cervical carcinogenesis, but the expression of stem cell markers in cervical carcinoma and HPV infection have yet to be investigated so far. A total of 94 cases of fresh cervical tissues, 116 cases of paraffin-embedded cervical specimens and 72 cases of peripheral blood samples were collected from Uighur women who were either diagnosed with cervical squamous cell carcinoma (SCC) or cervical intraepithelial neoplasia (CIN) II–III, or from healthy subjects (negative controls, NC). HPV infection was detected in tissue DNA by polymerase chain reaction (PCR) with a HPV genotyping kit. The mRNA expression levels of aldehyde dehydrogenase 1 family member A1 (ALDH1A1), nanog homeobox (NANOG), POU class 5 homeobox 1 (OCT4), SRY-box 2 (SOX2) and twist family BHLH transcription factor 1 (Twist1) were determined using reverse transcription-quantitative PCR (RT-qPCR). Histological analysis was performed in order to examine the protein expression of ALDH1A1 and OCT4 in paraffin-embedded tissue specimens by immunohistochemical staining and the plasma levels of those two proteins was measured by ELISA. RT-qPCR analysis indicated a significant increase in the mRNA expression of ALDH1A1 and OCT4 in CIN II–III and SCC tissue specimens compared with NC (P<0.05). Although the expression levels of NANOG, SOX2 and Twist1 were significantly higher in SCC compared with NC (P<0.05), no significant difference was revealed in CIN II–III tissues compared with SCC or NC (P>0.05). Subsequent analysis by immunohistochemistry staining confirmed that the upregulation of ALDH1A1 and OCT4 was also significantly increased in SCC and CIN II–III compared with controls at the protein level. Notably, ELISA analysis detected significantly higher levels of ALDH1A1 and OCT4 in the peripheral blood (plasma) of patients with SCC compared with healthy subjects. The upregulation of stem cell markers ALDH1A1 and OCT4 in cervical carcinoma and its precursor lesions, in particular in the peripheral blood, indicates that ALDH1A1 and OCT4 may serve as biomarkers for the early detection of cervical carcinoma or for the monitoring of treatment of patients.

Cell Abnormality in Pap Smear in Women with Postmenopausal Bleeding

Cancer cervix is a preventable and curable disease due to effective screening methods. Uterine cervix is ideal for screening due to easy accessibility for inspection, palpation and exfoliative cytology. The Pap smear is a screening test for cervical cancer, and with appropriate follow-up it can reduce cervical cancer incidence by up to 80%. This study includes fifty peri and postmenopausal women, cervical smears were taken in the Out-patient Clinic of Gynecology and Obestetrics Department and Pap stain was used for each sample, and the criteria of Bethesda (2014) was used for the diagnosis of each case. Bleeding was the main complaint in 92% patient and the remaining 8% complained from vaginal discharge and itching. Thirty nine patients were negative for intraepithelial lesion or malignancy (non-neoplastic), eight showed neoplastic changes, and 3 samples were insufficient for cytological interpretation. Two out of the 8 cases showed neoplastic lesions were atypical squamous cells of undetermined significance (ASCUS), two diagnosed as atypical squamous cells cannot exclude HSIL (ASC-H), 3 were high grade squamous intraepithelial lesions (HSIL) and one cases had features of squamous cell carcinoma (SCC). Six out of 39 samples showed only pure atrophy, three showed follicular cervicitis, three had features suggestive of Tichomonas vaginalis infection, one diagnosed as HSV infection, one showed bacterial vaginosis and eleven cases showed nonspecific inflammation. Non-neoplastic cases included also six cases showed metaplastic changes and eight had normal cytological findings. Conclusion: cervical smears is important in early detection of cervical carcinoma and its precursors in Sohag community as an easy, costless, accessible, and reliable manner and Bethesda system (2014) is beneficial for accurate diagnosis.

Human papiloma virus testing in the cervix of high-risk women: A hospital-based clinicopathological, colposcopic, and cytogenetic study

Background: The role of human papillomavirus (HPV) in the etiopathogenesis of precancerous and cancerous lesions of the cervix has been proven beyond doubt. Uterine cervix is a privileged organ being accessible and easily examined for lesions that can be extirpated in noninvasive stage, thus affecting a complete cure. Many different modalities for early detection of cervical lesions have been adopted, the most cost-effective being the Pap smear (Papanicolaou test). HPV DNA hybrid capture assays can be specifically used for detection of HPV DNA. Objectives: The purpose of this study was to estimate HPV positivity in high-risk women and to evaluate its relationship with age, parity, and other risk factors. Besides, it was carried out to evaluate the results of cytology, colposcopy, histopathology and HPV hybridization in early detection of cervical carcinoma, and to evaluate each parameter in the present setup. Materials and Methods: This was a hospital-based prospective study carried out from April 2006 to March 2007. Two hundred prospective patients were enrolled to study HPV positivity among high-risk women. Pap smears were taken and microscopically studied according to the Bethesda System 1988. Patients with atypical squamous cell of undeterminate significance (ASCUS) were then subjected to hybrid capture HPV test. Colposcopy examination and colposcopically-directed biopsies were taken in all the cases. Results: Most of the patients with lesions suggestive of HPV belonged to younger age group (21–30 years), and there was a significant increase in epithelial abnormalities with advancing age (p < 0.05). Inflammatory smears were seen in 70 patients (35%); 40 patients (20%) reported as ASCUS were subjected to High Risk Capture II assay (for HPV 16, 18, 45, 56, 58) and high-risk HPV DNA was found in 20 (50%) of the patients. The sensitivity of cytology was only 61%, histopathology could detect 24 (12%) additional cases of dysplasia compared to cytology, indicating a low sensitivity of Pap smear. Colposcopy correlated well with histopathology with a comparatively high sensitivity (80%). Conclusion: We conclude that cytology will continue to be a major screening method for detection of cervical lesions due to its low cost and easy availability. We also conclude that HPV DNA testing is a very sensitive and highly reproducible test but cannot be used as a mass screening procedure due to its expensive nature and its inaccessibility to the common masses.

Prevalence of human papilloma virus in cervical smear by DNA PCR testing and its comparison with pap smear

Introduction: Cervical cancer is one of the leading causes of cancer in women worldwide. Cervical cancer kills more women in India than anywhere in the world. There is good evidence that IIPV infection precedes the development of carcinoma cervix by a number of decades and that persistent infection with HPV is necessary for the development and progression of pre-cancerous lesions of cervix to cancer. This study was carried out to assess the prevalence of HPV infection in women attending gyneacology OPD in tertiary care hospital and to study sensitivity and specificity of Pap smear in detecting HPV as compared to HPV DNA PCR Material & Methods: This was a Hospital based Observational study in which all women visiting gyneacology OPD with gyneacological complaints were included in the study. A total of one thousand women were screened for HPV with pap smears and HPV DNA PCR test. Results: Out of the total of1000 women tested, 283 (28.3%) were found to be positive for HPV using HPV DNA PCR and 77 (7.7%) tested positive on PAP smear examination. Highest prevalence (31.2%) of HPV infection was seen in marriage age group of 16-20 and higher prevalence (57.1%) of HPV infection was also seen in women having more than 3 children. Pap smear was found to be 16.6% sensitive and 95% specific, whereas Positive Predictive Value and Negative Predictive Value was found to be 61% and 74% respectively. Discussion: The study reveals HPV prevalence rate of 28.3% in women attending gynaecology OPD of a tertiary care hospital and also prevalence of HPV was found to be highest in sexually active individuals with parity of 3 or more. These results are in agreement to many published national and international studies [12,13,14]. The study results also indicate lower sensitivity and higher specificity of Pap smear in detecting HPV infection, however it still remains the most important practicably available test in early detection of cervical carcinoma.

Knowledge of HPV infection and Pap testing among young women in Serbia

⁎ Corresponding author. Clinic of Oncological Surgery, Oncology Institute of Vojvodina, Institutski put 4, 21204 Sremska Kamenica, Serbia. Tel.: +381 214805548; fax: +381 21613741. E-mail address: aljosa.m@eunet.rs (A. Mandic). The high incidence rate of cervical cancer in Serbia highlights the need for a more detailed overview of this issue than has already been undertaken nationally [1]. National screening programs for the early detection of cervical carcinoma have not been implemented in the Serbian health system, so additional effort should be made within the healthcare and education systems to inform the population about the importance of regular gynecologic examinations and the risk factors that can lead to the development of cervical cancer. The principal aim of the present study was to assess the extent to which young women in the province of Vojvodina, Serbia, were informed about human papillomavirus (HPV) infection as a risk factor for the development of precancerous/cancerous lesions of the cervix and about the importance of the Papanicolaou (Pap) test and gynecologic examinations in identifying such lesions. The present study was performed between November 1 and December 20, 2009. It involved 361 women aged 17–27 years, who were divided into 3 groups: group A, comprising 117 final-year secondary school students from the grammar and medical schools in Sombor, Serbia (aged 17–19 years [mean, 17.9 years]); group B, comprising 128 students from the Faculty of Medicine at the University of Novi Sad, Novi Sad, Serbia (aged 19–27 years [mean, 22.8 years]); and group C, comprising 116 students from other faculties at the university (aged 19–27 years [mean, 20.8 years]). All participants completed an anonymous survey of 15 questions, includingquestions about age, sexual activity, knowledge of the Pap test, and knowledge of HPV infection as a risk factor for the development of precancerous/cancerous lesions of the cervix (Table 1). Ethics approval was not required, and informed consent was not needed because of the anonymous nature of the survey. Statistical analysis (Fisher exact test) was performed using STATISTICA version 9.0 (University of Novi Sad, Novi Sad, Serbia). Pb0.05 was considered to be statistically significant. The results of the survey indicated that 46 (39.3%) women in group A, 15 (11.7%) women in group B, and 23 (19.8%) women in group C had not engaged in sexual intercourse, and that 35 (29.9%) women in group A, 19 (14.8%) women in group B, and 15 (12.9%) women in group C had first engaged in sexual intercourse between the ages of 15 and 16 years. Of thewomenwhowere sexually active, themajority (56/71 [78.9%] in groupA, 88/113 [77.9%] in groupB, and78/93 [83.9%] in groupC)used condoms for protection against sexually transmitted diseases. Correct answers about the area from which smears are taken for cytopathologic analysis were given by 103 (88.0%) women in group A, 126 (98.4%)women in groupB, and101(87.1%)women in groupC.All of the women in group A, 127 (99.2%) women in group B, and 111 (95.7%) women in group C agreed that the Pap test is an important diagnostic tool in the prevention of cervical cancer. Of the 121 women in groups B and C who were older than 21 years of age, 44/69 (63.8%) in group B and 24/52 (46.2%) in group C had undergoneaPap test; this differencewas statistically significant (Pb0.05). Young sexually active women's knowledge of the necessity for regular Pap testing was high in all 3 groups in the present study; however, there was a significant difference between the women in groups A/B and those in group C in terms of knowledge of HPV (Pb0.001). University medical students (group B) knew much more about HPV as a sexually transmitted infection than did secondaryschool students (group A) and university students from other faculties (group C) (P=0.001). Compared with group B, a lower proportion of women in groups A and C knew about men being significant transmitters of the HPV infection and about the HPV vaccine. In the present study, knowledge of HPV as a risk factor for the development of precancerous/cancerous lesions of the cervix was similar to results obtained in other studies [2–4]. The implementation of a healthcare and education program in Serbia is an ideal basis from which to raise awareness among the general population of the need for a national screening program for the early detection of cervical carcinoma. The need for academically educated women to be further educated about HPV (as indicated by the present study) indirectly suggests a requirement for better medical education among the general population. This would significantly raise the efficiency of screening programs, which must be implemented in the Serbian national health system as soon as possible.

Screening for cervical carcinoma using visual inspection with acetic acid

Objective: To assess the performance of visual inspection with acetic acid (VIA) as a screening test for early detection of cervical carcinoma in the Dakahlia Governorate in Egypt. Methods: Diluted acetic acid (5%) was applied to the cervix during routine gynecologic examination. Women with positive results were referred for colposcopy. Those with negative results were referred for colposcopy only when they had clinical indications. Results: Among the 5000 women who were screened using VIA, 409 were referred for colposcopy. Cervical intraepithelial neoplasia (CIN) was diagnosed in 151 (60%) of the 253 women with positive screening results and in 4 of the 156 women with negative screening results. There were 39 women with high-grade and 116 with low-grade CIN. The sensitivity and negative predictive value of the VIA screening test was 97%. Its positive predictive value was 60% for all grades of CIN and 90% for high-grade CIN. Conclusion: Visual inspection with acetic acid, although associated with a relatively high rate of false-positive results, is a valuable test for the screening of cervical carcinoma.

Characterization of the Monoclonal Antibody Specific to Human S100A2 Protein

Background: The S100A2 gene, also known as S100L or CaN19, encodes a protein comprised of 99-amino acids, is a member of the calcium-binding proteins of EF-hand family. According to a recent study, this gene was over-expressed in several early and malignant carcinomas compared to normal tissues. To elucidate the role of S100A2 protein in the process during carcinogenesis, production of monoclonal antibody specific to the protein is essential. Methods: First, cDNA sequence coding for ORF region of human S100A2 gene was amplified and cloned into an expression vector to produce GST fusion protein. Recombinant S100A2 protein and subsequently, monoclonal antibody to the protein were produced. The specificity of anti-S100A2 monoclonal antibody was confirmed by immunoblot analysis of cross reactivity to other recombinant proteins of S100A family (GST-S100A1, GST-S100A4 and GST-S100A6). To confirm the relation of S100A2 to cervical carcinogenesis, S100A2 protein in early cervical carcinoma tissue was immunostained using the monoclonal antibody. Results: GST-S100A2 recombinant protein was purified by affinity chromatography and then fusion protein was cleaved and S100A2 protein was isolated. The monoclonal antibody (KK0723; Korean patent pending #2001-30294) to the protein was produced and the antibody did not react with other members of EF-hand family proteins such as S100A1, S100A4 and S100A6. Conclusion: These data suggest that anti-S100A2 monoclonal antibody produced in this study can be very useful for the early detection of cervical carcinoma and elucidation of mechanism during the early cervical carcinogenesis. (Im m u ne N etw ork 2003; 3(1):16-22)

Consequences of neural network technology for cervical screening: Increase in diagnostic consistency and positive scores

Screening programs for the early detection of cervical carcinoma are criticized because of the problem of false-negative diagnoses. A successful approach for solving this problem is applying neural network technology (PAP-NET) to assist the cytotechnologist (CT) in finding the (few) abnormal cells in the smear. In 3 consecutive years (1992, 1993, and 1994), 25,767 smears were screened conventionally and 65,527 with the aid of PAPNET by 7 CTs. For each CT, the scores for atypias of undetermined significance, squamous or glandular (ASCUC/AGUS according to the Bethesda classification system), indicated by Positive 1, for low grade precursor lesions, by Positive II, for high grade lesions and invasive carcinoma, by Positive III, were calculated for both screening methods. The histologic scores were also calculated. The mean positive scores of the seven CTs were higher for PAPNET than for conventional screening, and the coefficients of variability were lower. For Positive III smears, the consistency in screening was significantly higher for PAPNET than for conventional screening. The higher histologically positive scores for carcinoma in situ and invasive carcinoma indicated an increased screening sensitivity. As demonstrated by the improvement in the performances of all CTs involved, screening efficacy was enhanced by the use of neural network technology.

The role of the nurse in the early detection of cervical carcinoma in a developing country

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