Early Detection Of Cervical Neoplasia Research Articles

Cervical Cancer Screening Program by Visual Inspection: Acceptability and Feasibility in Health Insurance Companies.

Objective. To assess willingness to participate and diagnostic accuracy of visual inspection for early detection of cervical neoplasia among women in a health insurance company. Patients and Method. Cervical cancer screening was systematically proposed to 800 women after consecutive information and awareness sessions. The screening method was visual inspection with acetic acid (VIA) or Lugol's iodine (VILI). Results. Among the 800 identified women, 640 (82%) have accepted the screening, their mean age was 39 years, and 12.0% of them were involved in a polygamist couple. 28.2% of women had prior cervical screening. VIA has been detected positive in 5.9% of women versus 8.6% for VILI. The sensitivity was 72.9% and specificity was 95.2% for VIA versus 71.2% and 97.3% for VILI respectively. The histological examination highlighted a nonspecific chronic cervicitis in 4.6%, CIN1 lesions in 5.91%, and CIN2/3 in 1.2% of the cases. Conclusion. Cervical cancer screening by visual inspection showed appropriate diagnostic accuracy when used to detect early cervical lesions. It is a simple and easy to perform method that could be introduced progressively in the health insurance policy while waiting for a national screening program.

Comparison Between Pap Smear and Via As Screening For Cervical Lesions

Introduction: An important reason for higher cervical cancer incidence in developing countries is lack of effective screening programs like pap smear, aimed at detecting precancerous conditions before they progress to invasive cancer. The potential difficulties in implementing cervical cytology based screening in low-resource settings have prompted the investigation of accuracy of alternative low technology tests such as Visual inspection with acetic acid application [VIA], Visual inspection with acetic acid application with magnification [VIAM], visual inspection on Lugol’s Iodine application [VILI] in early detection of cervical neoplasia .In our study we compared pap smear with VIA to study the accurarcy of VIA as it is simpler and easier technique to be used as screening in low resource settings. Aim: This is a hospital based descriptive, prospective study to evaluate validity of pap smear and VIA techniques as screening tests in identifying cervical lesions. Materials And Methods: After general and systemic examination as a routine,visual local pelvic examination including visualisation of cervix and vagina per speculum and the findings are documented in the proforma .Then VIA and pap smear are done in that order, if any of these tests are positive then cervical biopsy will be taken and further advise to the subject is given. Results: A total of 313 women were involved in the study. The sensitivity of pap smear is 54.5% specificity is 98.9% while that of VIA 95.4% and 97.9%respectively. We found that VIA accuracy was comparatively more than that of pap smear. Conclusion: In low resource settings, usefulness of VIA is more than that of pap smear. We suggest to perform VIA in all the women inspite of having pap smear facility to improve detection rate of cervical lesions and provide better patient councelling and treatment.

The Mitochondrial Antisense ncRNAs are Down-Regulated in Early Cervical Carcinoma

Background: Cervical cancer is the third most common disease and the fourth leading cause of death in female’s worldwide. Treatment of this disease is successful when detection is at early neoplasic stages. Hence, multiple efforts have been pursued for early detection of cervical neoplasia. The aim of this study was to analyze the differential expression of mitochondrial non-coding RNAs or ncRNA (sense and antisense) in normal and neoplastic cervical biopsies as a potential tool for diagnostic of cervical cancer. Methods: The expression pattern of the sense and the antisense mitochondrial ncRNAs in cervical biopsies was carried out by chromogenic in situ hybridization (ISH). We examined 17 normal cervical tissues, 108 early and late neoplasias and 24 invasive cervical carcinomas. The hybridization results were compared with the diagnostic of each specimen carried out by pathologists. Results: Like normal human keratinocytes, normal cervical epithelium expresses the sense and the antisense mitochondrial ncRNAs at the basal layer of the epithelium. Interestingly, ISH reveals that the antisense transcripts are always localized in the nucleus of basal cells in normal cervical epithelium. Early and late cervical intraepithelial neoplasia as well as invasive cervical carcinoma expresses the sense transcript. In contrast, the antisense transcripts are down-regulated in early and late neoplasia and in invasive cervical carcinoma. Conclusions: This pilot study indicates that down-regulation of the antisense mitochondrial transcripts at early stages of cervical neoplasia can be explored as a diagnostic tool for early cervical neoplasia.

Visual screening for early detection of cervical neoplasia in Angola

Objective A cross-sectional study in Angola to evaluate the feasibility of cervical screening using visual inspection with acetic acid (VIA) or Lugol's iodine (VILI) to detect and treat cervical intraepithelial neoplasia (CIN). Methods All 8851 women screened by trained nurses received colposcopy and/or colposcopically-directed biopsies. The final disease status was based on histopathology or colposcopy when no or inadequate biopsies were done. The sensitivity, specificity, and predictive values of tests to detect CIN 2–3 were calculated. Results VIA was positive in 6.6% and VILI in 32.0% of the women. The positivity rates increased with time only for VILI. CIN 2–3 was diagnosed in 75 women and invasive cancer in 57. The sensitivity and specificity was 70.7% (95% CI, 59.0%–80.6%) and 94.5% (95% CI, 94.0%–95.0%) respectively for VIA, and 88.0% (95% CI, 78.4%–94.4%) and 68.9% (95% CI, 67.9%–69.9%) for VILI. Ninety percent of women detected with CIN received treatment. Treatment was given on the same day as screening to one-third of the 374 women treated with cryotherapy/LEEP. No major complications or adverse effects were associated with treatment. Conclusion It was feasible to screen with both visual tests and treat women with CIN in Angola. VILI was less specific than VIA, implying subjectivity in interpreting test results.

Early detection of cervical neoplasia by Raman spectroscopy

Early detection of malignant tumours, or their precursor lesions, improves patient outcome. High risk human papillomavirus (HPV), particularly HPV16, infection can lead to the development of uterine cervical neoplasia, and therefore, the identification in clinical samples of the effects of HPV infection may have clinical value. In this report, we apply Raman microspectroscopy to live and fixed cultured cells to discriminate between defined cell types. Raman spectra were acquired from primary human keratinocytes (PHK), PHK expressing the E7 gene of HPV 16 (PHK E7) and CaSki cells, an HPV16-containing cervical carcinoma-derived cell line. Averaged Raman spectra showed variations, mostly in peaks originating from DNA and proteins, consistent with HPV gene expression and cellular changes associated with neoplasia, in both live and fixed cells. Principal component analysis produced good discrimination between the cell types, with sensitivities of up to 100% for the comparison of fixed PHK and CaSki. These results demonstrate the ability of Raman spectroscopy to discriminate between cell types representing different stages of cervical neoplasia. More specifically, this technique was able to identify cells expressing the HPV 16 E7 gene accurately and objectively, suggesting that this approach may be of value in diagnosis. Moreover, the ability to detect the effects of the virus in fixed samples also demonstrates the compatibility of Raman spectroscopy with current cervical screening methods. (c) 2007 Wiley-Liss, Inc.

Evaluation of RNA Markers for Early Detection of Cervical Neoplasia in Exfoliated Cervical Cells

Numerous molecular biomarkers have been suggested for early detection of cervical cancer, but their usefulness in routinely collected exfoliated cells remains uncertain. We used quantitative reverse transcription-PCR to evaluate expression of 40 candidate genes as markers for high-grade cervical intraepithelial neoplasia (CIN) in exfoliated cervical cells collected at the time of colposcopy. Samples from the 93 women with CIN3 or cancer were compared with those from 186 women without disease matched (1:2) for age, race, and high-risk human papillomavirus status. Normalized threshold cycles (C(t)) for each gene were analyzed by receiver operating characteristics to determine their diagnostic performance in a split sample validation approach. Six markers were confirmed by an area under the curve >0.6 in both sample sets: claudin 1 (0.75), minichromosome maintenance deficient 5 (0.71) and 7 (0.64), cell division cycle 6 homologue (0.71), antigen identified by monoclonal antibody Ki-67 (0.66), and SHC SH2-domain binding protein 1 (0.61). The sensitivity for individual markers was relatively low and a combination of five genes to a panel resulted in 60% sensitivity with 76% specificity, not positively increasing this performance. Although the results did not indicate superiority of RNA markers for cervical cancer screening, their performance in detecting disease in women referred for colposcopy suggests that the genes and pathways they highlight could be useful in alternative detection formats or in combination with other screening indicators.

Lésions ano-génitales liées à l'infection par les papillomavirus humains chez la femme

Human papillomaviruses (HPV) are the most prevalent sexually-transmitted agents worldwide. HPV are small circular double-stranded DNA epitheliotropic viruses that exhibit either cutaneous or mucosal specificity. Most HPV infections are self-limiting and are spontaneously cleared within months or years. However, infections may persist and result in a variety of benign, pre-malignant and malignant tumors. Cytological and histopathological abnormalities associated with HPV infections of the male and female lower anogenital tract include condylomata, low-grade and high-grade squamous intraepithelial lesions which are incipient cancers, and squamous cell carcinomas. The modal time between HPV infection occurring in the late teens or early 20 s and precancer peaking around 30 years of age is 7-10 years. Women detected with invasive cancers tend to be an average 10 years older than women with high-grade disease. The natural history of cervical cancer reveals that infection with high-risk types may lead to low-grade or high-grade intraepithelial lesions. High-grade lesions may progress to cervical carcinoma if not treated. The purpose of screening, in addition to detecting cervical cancers at an early stage, is to detect and remove high-grade lesions and thus prevent the potential progression to cervical carcinoma. Early detection of cervical neoplasia is possible with regular Pap smears performed from 21 to 70 years of age. In case of abnormal Pap smear, a biopsy performed under colposcopy will allow the diagnosis of cervical lesion. Cancer of the cervix is the second leading cause of cancer related deaths among women across the world (3,400 new cases in France in 2000).

Gene expression profiling of dysplastic differentiation in cervical epithelial cells harboring human papillomavirus 16

Molecular events occurring with high-risk human papillomavirus (HPV)-associated dysplastic differentiation of cervical epithelial cells are largely unknown. This study used differential display PCR to identify expression changes between nondifferentiating monolayer and differentiated organotypic (raft) cultures of W12 keratinocytes. These cells were originally derived from a clinical biopsy of HPV 16-positive dysplastic cervical epithelium and retain high-risk HPV 16 and the ability to differentiate, albeit with dysplastic morphology. Using this model system we identified 84 genes with changed expression during dysplastic differentiation. Most (70/84, ≈80%) were down-regulated with differentiation, consistent with a restriction of expression during terminal differentiation. Twenty-two genes had no known function and 6 novel expressed sequence tags were identified among this group. Of the 62 genes with known functions, 25 belonged to transcription-, translation-, and posttranslation-related categories and 30 had functions associated with neoplastic initiation/progression, calcium signaling, epithelial differentiation, and structure remodeling. Some of the genes with altered expression identified in this model of dysplastic differentiation may be useful biomarkers for early detection of cervical neoplasia and other HPV-associated oropharyngeal and anogenital cancers.

Concurrent evaluation of visual, cytological and HPV testing as screening methods for the early detection of cervical neoplasia in Mumbai, India.

Naked eye visual inspection with acetic acid (VIA), magnified VIA (VIAM), visual inspection with Lugol's iodine (VILI), cytology and human papillomavirus (HPV) testing were evaluated as screening methods for the detection of high-grade squamous intraepithelial lesions (HSIL) of the uterine cervix in a cross-sectional study in Mumbai, India. Cytology, HPV testing, VIA, VIAM and VILI were carried out concurrently for 4039 women aged 30-65 years. All women were investigated with colposcopy and biopsies were taken from 939 women who had colposcopic abnormalities. The reference standard for final disease status was histology or negative colposcopy. The presence of HSIL was confirmed in 57 women (1.4%). The test characteristics for each method were calculated using standard formulae. The sensitivities of cytology, HPV testing, VIA, VIAM and VILI were 57.4%, 62.0%, 59.7%, 64.9%, and 75.4%, respectively (differences were not statistically significant). The specificities were 98.6%, 93.5%, 88.4%, 86.3%, and 84.3%, respectively. Adding a visual test to cytology or HPV testing in parallel combination resulted in a substantial increase in sensitivity, with a moderate decrease in specificity. The parallel combination of VILI and HPV testing resulted in a sensitivity of 92.0% and a specificity of 79.9%. As a single test, cytology had the best balance of sensitivity and specificity. Visual tests are promising in low-resource settings, such as India. The use of both VIA and VILI may be considered where good quality cytology or HPV testing are not feasible. The sensitivity of cytology and HPV testing increased significantly when combined with VIA or VILI.

The role of low-level magnification in visual inspection with acetic acid for the early detection of cervical neoplasia

Several studies have investigated the accuracy of naked eye visual inspection with acetic acid (VIA) in the early detection of cervical neoplasia. It is not clear whether low-level (2–4×) magnification (VIAM) can improve the sensitivity and specificity of VIA. The accuracy of both VIA and VIAM, provided by independent health workers, were evaluated in three cross-sectional studies involving 18,675 women aged 25–65 years in Kolkata and Mumbai in India. All screened women were investigated with colposcopy and biopsies were obtained based on colposcopy findings. The final disease status was based on the reference standard of histology (if biopsies had been taken) or colposcopy. Data from the studies were pooled to calculate the test characteristics for the detection of high-grade squamous intraepithelial lesions (HSIL). 14.1% and 14.2% were positive on testing with VIA and VIAM respectively. Two hundred twenty-nine were diagnosed with HSIL and 68 with invasive cancer. The pooled sensitivity, specificity, positive and negative predictive values for VIA in detecting high-grade squamous intraepithelial lesions (HSIL) were 60.3% (95% CI: 53.6–66.7), 86.8% (95% CI: 86.3–87.3), 5.9% (95% CI: 5.0–7.0), and 99.4% (95% CI: 99.2–99.5), respectively. The values were 64.2% (95% CI: 57.6–70.4), 86.8% (95% CI: 86.2–87.3), 6.3% (95% CI: 5.3–7.3) and 99.4% (95% CI: 99.3–99.6), respectively, for VIAM. Low-level magnification did not improve the test performance of naked eye visualization of acetic acid impregnated uterine cervix.

Molecular markers for early detection of cervical neoplasia.

Viral Exanthems and Herpesvirus Branch, Division of Viral and Rickettsial Diseases, National Center forInfectious Diseases, Centers for Disease Control and Prevention, Public Health Service, US Department of Healthand Human Services, Atlanta, GA, USA1. IntroductionIn the United States, cervical cancer screening pro-grams based on exfoliated cervical cytology (Papsmears) have significantly reduced the incidence of in-vasive cervical cancer. As a result of this success,current cervical cancer screening programs in the USare not directed at invasive disease, but at detection ofthe precursors of carcinoma, referred to as dysplasias,squamous intraepithelial lesions (SIL) or cervical in-traepithelial neoplasias (CIN). The progressive histo-logicandcytologicchangesthatoccurduringthemulti-step process of cervical carcinogenesis can be dividedinto multiple stages, early lesions known as CIN 1 orLSIL and high grade lesions known as CIN 2, 3 orHSIL. The natural history of these cervical cancer pre-cursor lesions is difficult to study because they are usu-ally biopsied or otherwise treated as soon as detected.However, it is clear that CIN 1 and 2 lesions are morelikelytoregressthantoprogresstoinvasivedisease[37,69]. While the risk of progression is greatest for CIN 3lesions, not all of these lesions progress and regressionis recognizedto occurin a significantbut variablenum-ber of cases [69]. Because of the slow rate of diseaseprogression, targeting early detection at CIN 3 lesionsis an effective strategy to avoid invasive cancer and at

Visual inspection with acetic acid and cytology in the early detection of cervical neoplasia in Kolkata, India

Visual inspection of the cervix after application of 3–5% acetic acid (VIA) is a potential alternative to cytology for screening in low-resource countries. The present study evaluated the performance of VIA, magnified visual inspection after application of acetic acid (VIAM), and cytology in the detection of high-grade cervical cancer precursor lesions in Kolkata (Calcutta) and suburbs in eastern India. Trained health workers with college education concurrently screened 5881 women aged 30–64 years with VIA, VIAM, and conventional cervical cytology. Detection of well-defined, opaque acetowhite lesions close to the squamocolumnar junction; well-defined, circumorificial acetowhite lesions; or dense acetowhitening of ulceroproliferative growth on the cervix constituted a positive VIA or VIAM. Cytology was considered positive if reported as mild dysplasia or worse lesions. All screened women (N= 5881) were evaluated by colposcopy, and biopsies were directed in those with colposcopic abnormalities (N= 1052, 17.9%). The final diagnosis was based on histology (if biopsies had been taken) or colposcopic findings, which allowed direct estimation of sensitivity, specificity, and predictive values. Moderate or severe dysplasia or carcinomain situ(CIN 2–3 disease) was considered as true positive disease for the calculation of sensitivity, specificity, and predictive values of screening tests. 18.7%, 17.7% and 8.2% of the women tested positive for VIA, VIAM, and cytology. One hundred twenty two women had a final diagnosis of CIN 2–3 lesions. The sensitivities of VIA and VIAM to detect CIN 2–3 lesions were 55.7% and 60.7%, respectively; the specificities were 82.1% and 83.2%, respectively. The sensitivity and specificity of cytology were 29.5% and 92.3%, respectively. All the tests were associated with negative predictive values above 98%. VIA and VIAM had significantly higher sensitivity than cytology in our study; the specificity of cytology was higher than that of VIA and VIAM.

American Cancer Society Guideline for the Early Detection of Cervical Neoplasia and Cancer

An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical neoplasia and cancer, based on recommendations from a formal review and recent workshop, is presented. The new screening recommendations address when to begin screening, when screening may be discontinued, whether to screen women who have had a hysterectomy, appropriate screening intervals, and new screening technologies, including liquid-based cytology and HPV DNA testing.

The cost-effectiveness of cervical cancer screening for low-income elderly women

Controversy surrounds prevention policy for the elderly. While some cost-effectiveness analyses have been done for the general elderly population, to our knowledge no study has examined the provision of preventive services to a low-income elderly population. We conducted a study of the cost-effectiveness of a cervical cancer screening program for infrequently screened elderly women attending an urban municipal hospital clinic. The results of Papanicolaou testing were abnormal (malignant or premalignant) in 11 of 816 women screened. This early detection of cervical neoplasia saved $5907 and 3.7 years of life per 100 Papanicolaou tests. When average medical costs per year of life extended by screening were included, the program cost $2874 per year of life saved. Comprehensive sensitivity analyses performed on competing medical and economic points of view did not change the conclusion of a favorable cost-effectiveness ratio for screening. Our findings indicate that the benefits from some prevention programs for the elderly can offset the costs of these programs. More research is needed to guide public policy on prevention for selected population groups. (<i>JAMA</i>1988;259:2409-2413)

The Cost-effectiveness of Cervical Cancer Screening for Low-Income Elderly Women

Controversy surrounds prevention policy for the elderly. While some cost-effectiveness analyses have been done for the general elderly population, to our knowledge no study has examined the provision of preventive services to a low-income elderly population. We conducted a study of the cost-effectiveness of a cervical cancer screening program for infrequently screened elderly women attending an urban municipal hospital clinic. The results of Papanicolaou testing were abnormal (malignant or premalignant) in 11 of 816 women screened. This early detection of cervical neoplasia saved +5907 and 3.7 years of life per 100 Papanicolaou tests. When average medical costs per year of life extended by screening were included, the program cost +2874 per year of life saved. Comprehensive sensitivity analyses performed on competing medical and economic points of view did not change the conclusion of a favorable cost-effectiveness ratio for screening. Our findings indicate that the benefits from some prevention programs for the elderly can offset the costs of these programs. More research is needed to guide public policy on prevention for selected population groups.

Current use of the Papanicolaou smear.

The Papanicolaou smear is an extremely useful screening technique for early detection of cervical neoplasia. The recent clarification of cervical intraepithelial neoplasia (CIN) as a continuum of dysplasia has ramifications for management. The modern reporting scheme includes a narrative portion that gives the clinician information beyond the original Class I-V. This is especially helpful in interpretation of the atypical smear. The recent findings of invasive disease following an atypical smear and the malignant potential of condylomatous changes have resulted in early use of colposcopy in these clinical situations. This article discusses Papanicolaou smear technique, reporting classifications, and management of the patient who has an abnormal smear.