Cytology For Cervical Cancer Screening Research Articles

Assessing New Technologies for Cervical Cancer Screening

New technologies have been proposed to replace cervical cytology as the medium for cervical cancer screening, especially testing for human papillomavirus (HPV). Many of these alternatives have been endorsed because their single-test sensitivity is superior to that of cytology. The sensitivity of a single Pap test may be as low as 50%, but lifetime testing has significantly greater sensitivity, and other parameters are also important in defining the optimal screening test. Test accuracy depends not only on sensitivity but also on specificity and disease prevalence; both of these are problematic when considering HPV as a screen. A screening test also must be acceptable to both clinicians and patients. HPV testing is regarded as test for a sexually transmitted disease by many women. Clinicians often fail to appreciate the transient nature of HPV infection, prompting overly aggressive treatment that risks future preterm birth, and there is no consensus about strategies for follow-up of abnormal HPV screening results when obtained without concomitant cytology. An emphasis on sensitivity also may be inappropriate when most cervical cancers occur in unscreened women, for whom the sensitivity of testing is irrelevant. HPV testing and other technologies have substantial promise as tests that may replace cytology in cervical cancer screening, but obstacles are significant, and premature adoption of these methods may result in patient harm.

Tests auf das Humanpapillomavirus (HPV) in der Zervixkarzinomfrüherkennung

Cytology-based screening for cervical cancer has been criticised because of its high percentage of false-negative results. Considering HPV testing as an integral part of the screening process has been discussed as a way to address this issue in Germany. The aim of our study was to review trials comparing HPV testing with cytology in cervical cancer screening. Based on a systematic literature review, 14 studies with 85,820 women could be included. Generally HPV testing was more sensitive, but less specific than cytology. Based on the pooled data, sensitivity and specificity for HPV testing were 91% and 90%, respectively, whereas sensitivity and specificity for cytology amounted to 66% and 96%, respectively. Based on these results, including HPV testing in primary cervical cancer screening might lead to a reduction of false-negative results. Due the lower specificity false-positive test results would increase though.

Impact of colposcopy on management outcomes of patients with abnormal cervical cytology

With stringent cervical cytology screening programmes for women in reproductive age group, cervical cancer is, to a large extent, preventable. Back-up confirmatory colposcopic evaluation is necessary in order for cytology to have impact on cervical cancer-related morbidity and mortality. To track the management outcomes of abnormal cervical cytology and hence confer credence to the value of colposcopy in management of abnormal cervical cytology. Retrospective descriptive study. Kenya Medical Women Association Colposcopy Clinic. Correlation of cervical cytologic abnormalities with colposcopic outcomes and eventual management outcomes. The population was young, with 50.6% being 25-34 years old, and 59.3% less than 35 years of age. Parity was also low, with nearly 75% being para three or less. A substantial proportion of women had normal colposcopic findings (42.0, 26.7,18.6 and 11.1% for cytologic abnormalities CIN I, CIN II, CIN III and invasive carcinoma respectively). Colposcopic abnormality detection rate, irrespective of the severity of the lesion, increased with severity of cytologic lesion (from 58.0% CIN I to 89.0% for invasive carcinoma). The sensitivity of cervical cytology was 58, 59 and 65% for CIN I,II and III respectively, while respective specificity was 72, 71 and 85%. The concordance rates between cytological and colposcopic findings were 38.6, 32.5 and 60% for CIN I, II and III respectively. The eventual management outcome was operative (LEEP and Hysterectomy) in greater frequency as the severity of the cytologic lesion increased. Colposcopy has significant impact on the management outcomes of abnormal cervical cytology and is therefore an invaluable procedure in management of abnormal cervical cytology. For this reason, it is imperative that governments avail these services to all women, in addition to enforcing regular cytologic screening for cervical cancer.

Is Liquid-Based Cytology Better Than Conventional Cytology for Cervical Cancer Screening?

Liquid-based cytology is widely used for cervical cancer screening, but no large, randomized studies have assessed its accuracy. Italian investigators

Effect of an antepartum Pap smear on the coverage of a cervical cancer screening programme: a population-based prospective study

BackgroundAlmost one-third of Norwegian women aged 25–69 years invited to have a Pap smear do not attend during the recommended period, and thus constitute a population with high-risk of cervical cancer (CC). Since the incidence of precancerous lesions of the cervix peak with occurrence of pregnancies within the same decade in women aged 25 to 35 years of age, antepartum care presents an opportunity to offer a Pap smear thereby increasing the coverage of the programme. The study objective was to describe the effect of the antepartum Pap smear on the coverage of a cytological CC screening programme.MethodsAmong 2 175 762 women resident in Norway in 31.12.1996, all women who gave birth in 1996–7 were identified from the Medical Birth Registry of Norway. Attendance to the cervical cancer screening was assessed by linkage to the Cytology Registry separately for the pregnant and non-pregnant women cohorts. The results were stratified by age, history of previous Pap smear and history of invitation to the CC screening programme. Logistic regression was used to estimate the relative probabilities of having a Pap smear adjusted for age, screening history, and time since invitation, for pregnant and non-pregnant women, respectively.Results69% of the pregnant women had a Pap smear during one year of follow-up since beginning of the pregnancy with the majority taken during the antepartum period. Irrespectively of age or history of having a Pap smear, pregnant women were 4.3 times more likely to have a Pap smear during follow-up compared to non-pregnant women. 63.2% of the pregnant women had a smear as response to the invitation letter compared to 28.7% of the non-pregnant women, OR = 2.1 (95% CI 1.9 to 2.4). As an indication of "over-screening", 5397 pregnant women (57.8%) with a smear shortly before the start of follow-up also had a new Papsmear, compared to 83 023 (32.3%) in non-pregnant.ConclusionPap smear screening during pregnancy increases the coverage of the CC screening programme. The contribution of the antepartum Pap smear to "over-screening" exists but its effect is modest in countries where women on average become pregnant after the start of recommended age of screening.

Conventional Pap smear and liquid based cytology for cervical cancer screening - a comparative study

The study was undertaken to evaluate liquid based cytology (Pap spin) and to compare the sensitivity of Pap spin with conventional Pap smear. Pap smears were taken from 160 patients with gynaecologic complaints with Ayre's spatula and endocervical cytobrush and slides prepared. The residual material on both the spatula and cytobrush were rinsed in Pap spin collection fluid and centrifuged. Direct smears were prepared from the cell button, fixed and stained by Papanicolaou stain. Colposcopy was performed in patients with abnormal smears and biopsy was performed in suspected malignant or dysplastic cases. LSIL and HSIL was diagnosed in 27 (64.4%) cases, mostly between 21-40 years, Commonest presenting complaint was discharge per vaginum seen in 68 (42.5%) cases. Cytological abnormality was found in 42 cases (26.2%) by Pap spin method, whereas conventional Pap smear detected abnormality in only 24 cases (15%). 133 cases (83.1%) were satisfactory for evaluation on Pap spin and 51 cases (31.9%) on conventional Pap smear. The commonest atypical finding on colposcopy was acetowhite area in 14 cases (31.1%). Sensitivity of Pap spin and conventional Pap smear was 97.6% and 53.7% respectively and specificity was 50% in each. Pap spin is strongly advocated in the best interest of public health as it improves the sample quality and reduces the likelihood of false negative results.

Cost is a Barrier to Widespread Use of Liquid-Based Cytology for Cervical Cancer Screening in Korea

This study aimed to document current cervical cancer screening practices of physicians in Korea. Questionnaires were distributed to 852 Korean obstetricians and gynecologists, who attended the 91st Conference of the Korean Society of Obstetrics and Gynecology held during May, 2005. Questionnaires were returned by 30.6% (260/852) of the recipients and 254 of these were eligible for analysis. Sixty-seven percent started cervical cancer screening women at age 20, and 65% replied that they would continue annual screening in a 35-yr-old woman with three consecutive normal cytologic tests. Over 65% of respondents preferred conventional cytologic screening to liquid-based cytology. The cost was a major determinant for selecting screening method. Fifty-three percent used the human papillomavirus DNA test as a triage for atypical squamous cells of undetermined significance. Our findings suggest that majority of Korean obstetricians and gynecologists in hospital prefer annual conventional cytologic testing to liquid-based cytology for financial reason.

Immunocytochemistry in liquid‐based cervical cytology: Analysis of clinical use following a cross‐sectional study

Cytological screening for cervical cancer is hampered by imperfect sensitivity and low inter-observer reproducibility. Human papillomavirus (HPV) testing lacks specificity as a primary screening method. Studies indicate that immunocytochemical detection of alterations caused by HPV in the host cells can optimise screening. Here, the potential of p16(INK4a) (cyclin-dependent kinase inhibitor p16) and MIB-1 (Ki-67 proliferation marker) as adjunct molecular markers for cervical lesions was investigated in a prospective, cross-sectional study of 500 samples in the framework of opportunistic screening in Flanders, Belgium. A consecutive series of 200 samples and 100 samples from the cytological categories ASC, LSIL and HSIL were investigated. Surepath samples were interpreted according to the Bethesda 2001 reporting system. HPV testing was done with MY09/MY11 consensus PCR. Immunocytochemistry for p16(INK4a) and MIB-1 was performed with an automated staining protocol. The number of immunoreactive cells/1,000 cervical cells was assessed. There was a higher mean number of p16(INK4A) and MIB-1 immunoreactive cells/1,000 cells in HSIL (4.06 +/- 1.93 and 11.13 +/- 2.83, respectively) compared to other cytological categories. Both markers showed a large spread in counts, for all categories. In cases of HSIL without immunoreactive cells for either marker, low cellularity and long-term storage in water were often the cause of false negativity. This study confirms that positive staining for p16(INK4a) and MIB-1 is highly correlated with presence of high-grade lesions. These markers could be used as adjuncts to increase the sensitivity of cytological screening as well as the specificity of the HPV test. However, clear methodological standards are needed for optimal performance of immunocytochemistry in a clinical setting.

Liquid-based cytology for cervical cancer screening

In multiple studies during the last decade, liquid-based cytology for cervical cancer screening has been shown to increase the detection rate for preneoplastic squamous intraepithelial lesions equal to or greater than the conventional Papanicolaou (Pap) smear method. Liquid-based collection and processing provide more representative cervical sampling than conventional smearing of the specimen on a glass slide. Currently, there are two test methodologies that are widely marketed and available to clinical laboratories, health systems and clinicians that undertake cervical cytology. The purpose of this article is to provide an overview of the methodology and performance of SurePath™ Liquid-Based Pap Test in cervical cytology screening. The SurePath liquid-based Pap test significantly reduces the unsatisfactory rate of Pap test slides, and detects a significantly higher number of low- and high-grade squamous lesions when compared with the conventional Pap smear technique. Biopsy confirmation shows that this increased detection does not come at a cost of decreasing specificity, and sensitivity for histologic dysplasia is equal to or greater than the best available data for the conventional Pap method. The SurePath collection vial provides residual cellular material for adjunctive out-of-the-vial molecular testing, including sexually transmitted diseases and oncologic biomarkers associated with cervical carcinoma. Finally, SurePath slides can be placed on an automated cervical cytology screening device (FocalPoint™), thus providing improved disease detection and enhanced laboratory productivity.

Human papillomavirus testing in cervical cancer screening

Human papillomavirus testing in cervical cancer screening

HPV DNA Testing as an Adjunct to Cervical Cytology

Although human papillomavirus (HPV) DNA testing now is available as an adjunct to cytology for cervical cancer screening, no definitive evidence shows

Interim guidance for the use of human papillomavirus DNA testing as an adjunct to cervical cytology for screening.

Human papillomavirus (HPV) DNA testing was recently approved by the Food and Drug Administration for use as an adjunct to cytology for cervical cancer screening. To help provide guidance to clinicians and patients when using HPV DNA testing as an adjunct to cervical cytology for screening, a workshop was cosponsored by the National Institutes of Health-National Cancer Institute, American Society of Colposcopy and Cervical Pathology (ASCCP), and American Cancer Society. Consensus was reached based on a literature review, expert opinion, and unpublished results from large ongoing screening studies. The conclusions of the workshop were that HPV DNA testing may be added to cervical cytology for screening in women aged 30 years or more. Women whose results are negative by both HPV DNA testing and cytology should not be rescreened before 3 years. Women whose results are negative by cytology, but are high-risk HPV DNA positive, are at a relatively low risk of having high-grade cervical neoplasia, and colposcopy should not be performed routinely in this setting. Instead, HPV DNA testing along with cervical cytology should be repeated in these women at 6 to 12 months. If test results of either are abnormal, colposcopy should then be performed. This guidance should assist clinicians in utilizing HPV DNA testing in an effective manner, while minimizing unnecessary evaluations and treatments.

P16INK4a as an adjunct marker in liquid-based cervical cytology.

Cytological screening for cervical cancer is hampered by high false negative rates. Inter-observer reproducibility needs optimizing. The potential of p16(INK4a) as a biomarker for cervical lesions was examined in a study of liquid-based cytology (LBC), HPV DNA testing by MY09/MY11 consensus PCR and type-specific PCRs and p16(INK4a) immunocytochemistry on a series of 291 patients selected from routine screening. Comparison of the number of p16(INK4a) immunoreactive cells/1,000 cells exhibited a significantly higher mean count in HSIL (8.80 +/- 1.13) than other cytological groups. The mean count of LSIL (1.09 +/- 0.18) was significantly higher than that of the negative group (0.82 +/- 0.40). ASC-H and HSIL combined showed a significantly higher mean count (6.46 +/- 1.17) than negative, ASC, ASC-US and LSIL. The mean count of immunoreactive cells/1,000 cells was significantly higher in HPV16 positive samples (3.22 +/- 0.72) than in samples containing infections with types of unknown malignant potential (0.83 +/- 0.26) or HPV negative samples (1.17 +/- 0.41). The mean count in infections with other high-risk HPV types (2.55 +/- 0.52) was significantly higher than that in HPV negative samples. Receiver-operating characteristic curves yielded a test accuracy (area under curve) of 0.76, 0.79, 0.88 and 0.95 for ASCUS, LSIL, ASC-H/HSIL and HSIL, respectively. Thresholds for 95% sensitivity were at 0.005, 0.007, 0.098 and 0.445 immunopositive cells/1,000 cells for ASCUS, LSIL, ASC-H/HSIL and HSIL, respectively. The 95% specificity threshold for the detection of HSIL was at 1.87 immunopositive cells/1,000 cells. P16(INK4a) immunocytochemistry can be used as an adjunct to LBC in cervical screening, because it has a good diagnostic accuracy to discriminate HSIL and ASC-H from other lesions. It could be used as a surrogate marker of high-risk HPV infections.

Screening of Cervical Cancer: Where Do We Go from Here?

Cytological screening of cervical cancer was initiated by a cytopathologist, George Papanicolaou, M.D., Ph.D. Dr. Papanicolaou was studying hormonal maturation of the human vaginal mucosa when he n...

Telomerase Assay and HPV 16/18 Typing as Adjunct to Conventional Cytological Cervical Cancer Screening

Objective: This study aims at exploring the potential use of telomerase activity assay and typing of human papillomaviruses (HPV) 16 and 18 in improving the identification of high-grade cervical intraepithelial neoplasia (CIN). Methods: From 86 women with normal cervical smears and from 114 patients with abnormal cervical smears cervical scrapings were collected. The telomerase activity was assayed using the Telomerase Repeat Amplification Protocol, and HPV was detected using consensus primers and specific primers for HPV 16 and HPV 18. Results: HPV 16 in cervical scrapes was significantly associated with high-grade squamous epithelial lesions on cytology and with high-grade CIN, i.e., CIN 2/3 on biopsy. The detection of HPV 18 or telomerase activity had no significant association with high-grade squamous intraepithelial lesions or high-grade CIN. Conclusion: The use of the telomerase activity assay in cervical scrapes, unlike HPV 16 typing, did not improve the detection of high-grade CIN.

Overexpression of p16(INK4A) as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri.

Cytological screening for cervical cancer or its precursors using Papanicolaou's smear test (Pap test) has been highly efficient to reduce the morbidity and mortality of cervical cancer. However, evaluation of the Pap test relies on subjective diagnostic parameters and is affected by a high rate of false-positive and false-negative results. More objective diagnostic parameters to identify truly dysplastic or neoplastic cells in cervical smears as well as in cervical biopsy samples would therefore avoid insecurity for many patients and the high screening costs associated with repeated testing. Cervical dysplasia is induced by persistent infections through high-risk types of human papillomaviruses (HPVs). Outgrowth of dysplastic lesions is triggered by increasing expression of two viral oncogenes, E6 and E7, which both interact with various cell cycle-regulating proteins. Among these is the retinoblastoma gene product pRB, which is inactivated by E7. pRB inhibits transcription of the cyclin-dependent kinase inhibitor gene p16(INK4a). Increasing expression of the viral oncogenes in dysplastic cervical cells might thus be reflected by increased expression of p16(INK4a). In line with this hypothesis, we observed marked overexpression of p16(INK4a) in all cervical intraepithelial neoplasm (CIN) I lesions (n = 47) except those associated with low-risk HPV types (n = 7), all CIN II lesions (n = 32), all CIN III lesions (n = 60) and 58 of 60 invasive cervical cancers. In contrast, no detectable expression of p16(INK4a) was observed in normal cervical epithelium (n = 42), inflammatory lesions (n = 48) and low-grade cervical lesions (CIN I) associated with low-risk HPV types (n = 7). Dysplastic cells could also be identified in cervical smears using a specific p16(INK4a) monoclonal antibody. These data demonstrate that p16(INK4a) is a specific biomarker to identify dysplastic cervical epithelia in sections of cervical biopsy samples or cervical smears.

PCR based high risk HPV testing is superior to neural network based screening for predicting incident CIN III in women with normal cytology and borderline changes

Background/Aims—To improve the accuracy of conventional cytology in cervical cancer screening, high risk human papillomavirus (HPV) testing and neural network based screening have been developed. This study assessed the power...

Has the use of pap smears reduced the risk of invasive cervical cancer in Guadalajara, Mexico?

In Mexico, cervical cancer is the leading cause of death due to cancer among women 35 years of age and older. Although cytologic screening for cervical cancer was introduced as a national program 24 years ago, the mortality rate for this disease has been increasing. A case-control study was undertaken. Cases were women younger than 70, with newly diagnosed invasive cervical cancer (ICC), who had been residing for at least the past year in the metropolitan area of Guadalajara. They were selected from 5 hospitals belonging to the Mexican National Health System. Controls were women without cervical cancer who were treated in the same health center as the corresponding case. Analysis included 143 cases and 311 controls. Information on risk factors for cervical cancer and prior cervical cytologic screening was obtained through a standardized personal interview. Overall, 54% of the cases reported having had a cervical cytology compared with 82% of controls. When compared with unscreened women, those who had ever had a Pap smear had a significantly lower risk of cervical cancer (OR = 0.3, 95% CI 0.2-0.4), and the protective effect persisted for over 5 years. Utilization of Pap smears in the metropolitan area of Guadalajara exerted a protective effect on ICC. Of the 65 women who reported a negative history of Pap smears, 45 would not have contracted cancer if they had ever had a Pap smear.

Low efficiency of cytologic screening for cancer in situ of the cervix in older women

Cytologic screening for cervical cancer has proven to be beneficial in many countries, although the value of this intervention in women older than 50 years remains controversial. The purpose of this study was to investigate the efficiency of detecting cancer in situ by means of a cytologic smear at different ages, with special emphasis on the benefit of screening in women above the age of 50. We analyzed 466,275 smears taken in an open cohort of 118,890 women in Sweden between 1969 and 1988. The number of cancers in situ detected per 1,000 smears, the detection ratio, was used as an outcome measure in univariate analyses and in multivariate regression models. Cancer in situ was detected in 1,076 women in the study cohort. The detection ratio peaked at ages 30 to 34 and decreased heavily during the next 15 years of age. The efficiency of taking smears at ages above 50 was only 20 per cent (OR, 0.19; 95% CI, 0.14-0.26) of that at ages 30 to 34. These results were not changed when adjusting for time period and time interval since the previous smear. In spite of a high incidence of invasive cervical cancer in older women, the benefit of cytologic screening to detect cancer in situ above the age of 50 is uncertain.

Trends in cervical cancer incidence in the District of Florence

The trend in cervical cancer incidence in the District of Florence from 1975 to 1989 was investigated. Tuscany Cancer Registry data were available since 1985. Incidence data from 1975 to 1985 were obtained through a retrospective survey of all the Departments of Pathology and Gynaecology in the district. Cytological screening for cervical cancer has been available in the district since 1973, and since 1980 active invitation of residents aged 25 to 59 years has been in use. A significant trend in decreasing incidence was evident for the overall population (P = 0.003) and for 40-49 (P = 0.028), 50-59 (P < 0.001) and 60-69 (P = 0.002) year age groups, whereas no significant trend was observed for the age group 30-39 years. An association between attendance to screening and reduced incidence was evident, in that a greater reduction was evident for those cohorts (ages 50-59 and 60-69) who had a higher compliance to screening 10-15 years before. If the decrease in cervical cancer incidence was spontaneous, a parallel decrease of CIN3, which is commonly assumed to be the precursor of invasive carcinoma, would be expected. On the contrary, the detection rate of CIN3 at first Pap test showed a significant increase in the study period. All these findings suggest that the observed reduction in cervical cancer incidence was mostly due to the effect of screening, and stress the need for optimising the coverage of the invited population.