Conventional Pap Test Research Articles

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.

The clinical impact of using p16(INK4a) immunochemistry in cervical histopathology and cytology: an update of recent developments.

Cervical cancer screening test performance has been hampered by either lack of sensitivity of Pap cytology or lack of specificity of Human Papillomavirus (HPV) testing. This uncertainty can lead to unnecessary referral and treatment, which is disturbing for patients and increases costs for health care providers. The identification of p16(INK4a) as a marker for neoplastic transformation of cervical squamous epithelial cells by HPVs allows the identification of HPV-transformed cells in histopathology or cytopathology specimens. Diagnostic studies have demonstrated that the use of p16(INK4a) immunohistochemistry substantially improves the reproducibility and diagnostic accuracy of histopathologic diagnoses. p16(INK4a) cytology has substantially higher sensitivity for detection of cervical precancer in comparison to conventional Pap tests. Compared to HPV DNA tests, immunochemical detection of p16(INK4a) -stained cells demonstrates a significantly improved specificity with remarkably good sensitivity. About 15 years after the initial observation that p16(INK4a) is overexpressed in HPV-transformed cells we review the accumulated clinical evidence suggesting that p16(INK4a) can serve as a useful biomarker in the routine diagnostic work up of patients with HPV infections and associated lesions of the female anogenital tract.

Vertical transmission of HPV in pregnancy. A prospective clinical study of HPV-positive pregnant women

Human papillomavirus (HPV) is the most common sexually transmitted infection. Data reporting vertical transmission of HPV from the mother to the fetus are inconsistent and scant. Vertical transmission may occur by hematogenic route (transplacental), or by ascending contamination, or through the birth canal, which may result in the dreaded and rare laryngeal papillomatosis. Infected sperm at fertilization is a potential route of infection, too. The objective of the study was to evaluate the rate of vertical transmission of HPV in HPV-positive pregnant women to their newborn infants, as well as the risk factors of HPV vertical transmission. The clinical material was provided by 136 pregnant women, aged 18-45 years. Out of this group, 30 (22.05%) women with abnormal Pap test and positive DNA HPV test were prospectively observed Neonatal status, i.e. DNA HPV from the nasopharyngeal smear was recorded in all infants during the perinatal period. The conventional Pap test was performed with the cervix brush in all women. The Bethesda 2011 classification system was applied. An average C Reactive Protein (CRP) concentration in the studied pregnant women was 711.6083 (Std Dev--12.93). The most frequent cytological findings in the cervical smears from the examined women were ASCUS, n = 13 (43.3%), then--LSIL, n = 10 (33.3%), HSIL--n = 5 (16.7%) and AGC--n = 2 (6.7%). In the neonates, the presence of LR HPV DNA was detected in 9 cases (30.0%) and HR HPV DNA in 7 cases (23.3%). Fourteen neonates (46.7%) tested HPV DNA negative in the perinatal period. HPV infection (incidental or chronic) is observed in approximately 22% of pregnant women from the Matopolska province. Neonatal HPV infection in HPV-positive women was observed in 53.3% of the subjects. CRP concentration > 10 mg/dl in the serum of pregnant women statistically significantly (p 0.001) reduces the risk of vertical transmission of HPV from the mother to the fetus.

A Comparison of 3 Ways of Conventional Pap Smear, Liquid-Based Cytology and Colposcopy vs Cervical Biopsy for Early Diagnosis of Premalignant Lesions or Cervical Cancer in Women with Abnormal Conventional Pap Test

The most cost effective method of prevention and detection of cervical cancer is the Pap smear. In abnormal Pap smear, colposcopy, endocervical curettage and biopsy will be done. Gold standard method in detecting cervical lesion is biopsy. Now in two ways conventional Pap smear and liquid base are routine diagnostic technique in Iran and given easily and cost-effectiveness of this method in the detection of cervical lesions to determine the sensitivity the objective of this study was compare three methods of Pap smear and colposcopy in detection of any lesion to gold standard biopsy in the positive ASC cases who referred to gynecologic Oncology Clinic of shahid Sadoughi University of Medical Science. This study is a descriptive analytic in 2009-2010 years on 150 cases of patients with Atypical Squamose Cell (ASC) results in previous pap smear ,conventional pap smear, liquid based pap smear, colposcopy and cervical biopsy had been done for all patient and finally data were analyzed with chi-square statistical test on spss ver 16 saftware. Average age of patients in this study was, 42 ± 9.9 year and reason for referring patients in 35.4% of cases was due to follow-up of abnormal results of previous Pap smear, in 30% bleeding, 12% Pain and 2.6% percent of cases was checking-up. In final results of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy any of the methods conventional and liquid based Pap smear and colposcopy were compared with cervical biopsy as a gold standard. The conventional Pap smear method had a sensitivity 51%, specificity 66.6%, PPV 96%, NPV was 8% and accuracy was 92%, about the liquid base Pap smear method, sensitivity was 55.3%, specificity was 77.7%, PPV was 97.5%, NPV was 10% and accuracy was 56/6%. About the colposcopy, sensitivity was70/9 % specificity 44/4%, PPV was 95.2%, NPV was 8/8% and accuracy was 69.3%. The relationship between sensitivity results of conventional Pap smear and colposcopy, with p<0.001 and between the results of sensitivity of liquid based cytology and colposcopy with p<0.01 relationship was significant. Colposcopy has the best efficacy in detecting any cervical lesion in compared with any other diagnostic technique. so that further studies with more detailed plans and bigger sample sizes are suggested for obtaining reliable result.

Evaluation of Conventional Pap Test for Cervical Intraepithelial lesions and Cancer in a Tertiary Hospital of Bangladesh

Objective: This study was aimed to evaluate the conventional Papanicolaou (Pap) test for detection of cervical intraepithelial lesions and cancer, with histopathologic association, in a tertiary hospital of a developing country. Methods : A crosssectional hospital-based study was carried out in a total of 550 women, who underwent Pap smear examination, followed by colposcopy. Specimen adequacy and reporting was assessed according to the revised Bethesda system. 195 of these women, either Pap test positive, colposcopically positive or both, subsequently had their cervical tissue examination done with routine histopathology, as histopathology is the gold standard and Pap smear test was compared with it. Results: Among the total of 195 positive cases, histologic diagnosis of 104 (53.33%) cases were negative for cervical intraepithelial lesions or cancer, 64 (32.82%) were cervical neoplasia grade I (CIN I), 19 (9.74%) showed features of cervical intraepithelial neoplasia grade 2 and 3 (CIN II and III) and 08 (04.11%) as squamous cell carcinoma. The sensitivity and specificity of Pap test were 89.01% and 91.31%, respectively. Positive predictive value was 91.01%, while the negative predictive value was 90.56%. Conclusion: The findings of this study will be utile in supporting some useful information of Pap test, which plays a potential role in detection of cervical cancer and its precursors in a developing country like Bangladesh, where HPV-DNA test or liquid-based cytology is too expensive. DOI: http://dx.doi.org/10.11566/cmoshmcj.v12i2.31 Chatt Maa Shi Hosp Med Coll J 2013; 12(2): 1-6

Human Papilloma Virus Frequency and Genotype Distribution in a Turkish Population

To determine human papillomavirus (HPV) frequency, genotypes and the relation between cervical smear results, risk factors and types in women living in Manisa, Turkey. A total of 410 women were included in the study. Cervical specimens were obtained for linear array HPV genotyping and pathological testing. Conventional Pap test and Bethesda system were used for evaluation of cytology specimens. A total of 410 women with a mean age of 34.9 years were tested. A positive result of any HPV was found in 35 patients (8.5%). Among them, 26 different serotypes of HPV were identified and the most frequent type was HPV 16 (28.5%) followed by type 45 and 53 (11.4%). Patients were infected by 65.7% high risk, 11.4% probable high risk and 22.9% low risk HPV types. Multiple HPV positive results were found in 13 patients (37.1%). Patients with single partner, history of abnormal smear or condyloma had positive HPV results and this was statistically significant (p<0.05). Correlation analysis showed a statistically weak relation between positive HPV and abnormal smear results (r=0.120). Determining HPV types of genital HPV infections is important for epidemiological studies. We have found the rate of positive HPV as 8.5% which implies the need for extended screening programs in order to diagnose oncogenic HPV at an early stage.

Negative Predictive Value of Pap Testing

To estimate the accuracy of Pap testing for women who are human immunodeficiency virus (HIV)-seropositive, with a focus on negative predictive value. Participants in the Women's Interagency HIV Study were monitored with conventional Pap tests every 6 months. After excluding those with abnormal Pap test results before study, cervical disease, or hysterectomy, women with negative enrollment Pap test results were monitored for development of precancer within 15 or 39 months, defined as a Pap test result read as high-grade squamous intraepithelial lesion, atypical glandular cells favor neoplasia, or adenocarcinoma in situ, or a cervical biopsy read as cervical intraepithelial neoplasia 2 or worse. Correlations between one or more consecutive negative Pap test results and subsequent precancer were assessed using Cox proportional hazards models. Among 942 HIV-infected women with negative baseline Pap test results, eight (1%) developed precancer within 15 months and 40 (4%) within 39 months. After three consecutive negative Pap test results, precancer was rare, with no cases within 15 months and 10 of 539 (2%) within 39 months. No women developed precancer or cancer within 39 months after 10 consecutive negative Pap test results. Risks for precancer within 15 months after negative Pap test result included current smoking (adjusted hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.2-2.0 compared with nonsmokers), younger age (adjusted HR 1.5, 95% CI 1.1-2.1 for women aged younger than 31 years compared with older than 45 years), and lower CD4 count (adjusted HR 11.8, 95% CI 1.3-2.3 for CD4 200-500/microliter, adjusted HR 2.2, 95% CI 1.6-2.9 for CD4 less than 200/microliter, compared with CD4 more than 500/microliter). Annual Pap testing appears safe for women infected with HIV; for those with serial negative tests, longer intervals are appropriate. II.

Distribution of human papillomavirus types, cervical cancer screening history, and risk factors for infection in Manitoba

We conducted a study to investigate the prevalence of human papillomavirus (HPV) infections in an opportunistic sample of women in Manitoba, Canada. We inquired about risk factors associated with HPV infections and linked the HPV typing results with the cervical cancer screening history of the participants. The study population included 592 women attending Papanicolaou (Pap) test clinics. After signing a consent form, participants were given a self-administered questionnaire on risk factors and received a conventional Pap test. Residual cells from the Pap tests were collected and sent for HPV typing. The mean age of the population was 43 years. A total of 115 participants (19.4%) had an HPV infection, 89 of whom had a normal Pap test. Of those who were HPV-positive, 61 (10.3%) had high-risk (Group 1) HPV. HPV-16 was the most prevalent type (15/115: 13.0% of infections). The most consistent risk factors for HPV infection were young age, Aboriginal ethnicity, higher lifetime number of sexual partners and higher number of sexual partners in the previous year. The prevalence of HPV types in Manitoba is consistent with the distributions reported in other jurisdictions. These data provide baseline information on type-specific HPV prevalence in an unvaccinated population and can be useful in evaluating the effectiveness of the HPV immunization program. An added benefit is in the validation of a proof of concept which links a population-based Pap registry to laboratory test results and a risk behaviour survey to assess early and late outcomes of HPV infection. This methodology could be applied to other jurisdictions across Canada where such capacities exist.

P1-S2.69 Prevalence of HPV infections in Metis and First Nations living in Manitoba, Canada

BackgroundInformation on human papillomavirus (HPV) prevalence among Aboriginal populations (First Nations, Métis, Inuit) in Canada remains scarce but is needed for informed public health programming. This need is reinforced by...

Should adequacy criteria in cervicovaginal cytology be modified after radiotherapy, chemotherapy, or hysterectomy?

The general criterion of an unsatisfactory Papanicolaou (Pap) test in the 2001 version of the Bethesda system is not applicable to patients after treatment with radiotherapy, chemotherapy, or hysterectomy. The current study was performed to determine whether specimen adequacy criteria for Pap tests should be modified for these conditions. Consecutive patients who underwent conventional Pap tests between March and August 2006 were reviewed. The original reports were done according to the 2001 Bethesda system, with cellularity criteria modified in patients with a history of radiotherapy, chemotherapy, or hysterectomy. The slides of these patients were reviewed again. The degrees of cellularity, obscuring red blood cells, and inflammation were recorded. The final analyses included 7033 patients for which there were complete data. The original interpretation was unsatisfactory in 4.4% of all samples. When the 1337 slides obtained from patients with a history of radiotherapy, chemotherapy, and/or hysterectomy were reviewed using the general satisfactory threshold of >8000 squamous cells/slide and <75% of the epithelium obscured, the incidence of unsatisfactory Pap tests increased from 4.3% to 13.2% (176 of 1337 slides). The odds ratios for unsatisfactory Pap tests for a history of radiotherapy, chemotherapy, and age >50 years were 2.70, 2.51, and 1.39, respectively. The majority of unsatisfactory Pap tests were because of low cellularity. The lower limits of adequate cellularity after radiotherapy or chemotherapy can be set at 2000 cells/slide, which can lower the unsatisfactory rate while at the same time resulting in no increase in the false-negative rate. Hysterectomy alone was not found to be associated with unsatisfactory Pap tests. In patients who received pelvic radiotherapy or chemotherapy, the incidence of low-cellularity Pap tests was unacceptably high. A lower cellularity (estimated 2000 cell/slide) could be used as a satisfactory threshold.

The Age-Specific Relationships of Abnormal Cytology and Human Papillomavirus DNA Results to the Risk of Cervical Precancer and Cancer

To estimate the relationship of human papillomavirus (HPV) detection and abnormal cytology with histologic diagnoses of cervical precancer and cancer. From 2003 to 2008 we examined the HPV, cytology, and diagnostic results from almost one million cervical cancer screenings done on women aged 30 and older who were members in Kaiser Permanente Northern California, a large health maintenance organization that introduced cotesting in 2003. Women were screened using conventional Pap tests and a DNA test for a pool of 13 high-risk HPV genotypes. Women with HPV-positive atypical squamous cells of undetermined significance and other abnormal cervical cytology, independent of their HPV results, routinely underwent colposcopy. Results were stratified by 5-year age groups from 30 to 64. High-grade squamous intraepithelial lesions (HSIL), atypical squamous cells, cannot exclude HSIL (ASC-H), and atypical glandular cells were more strongly associated with cervical intraepithelial neoplasia grade 3 while low-grade squamous intraepithelial lesions (LSIL) and HPV-positive atypical squamous cells of undetermined significance were more strongly associated with cervical intraepithelial neoplasia grade 2 (CIN2). Cervical cancer was most commonly found in women with HSIL and atypical glandular cells cytology. Human papillomavirus-negative women with ASC-H cytology were at a reduced but significant risk of CIN2 or more severe (CIN2+) (10.6%) compared with HPV-positive women with ASC-H cytology. Human papillomavirus-negative women with LSIL were at a 4.0% risk of CIN2+, and among women 50 and older, at a 0.5% risk of CIN2+ with no cancers were diagnosed. Human papillomavirus testing may be useful for triage for colposcopic referral for LSIL cytology in older women but not for ASC-H cytology at any age. II.

Triage of women with atypical squamous cells of undetermined significance (ASC-US): Results of an Italian multicentric study

Objectives To compare the performance of immediate colposcopy, repeat Pap test and HPV test as triage options for women diagnosed as having atypical squamous cells of undetermined significance (ASC-US) while attending organised screening for cervical carcinoma in five centres of the Veneto region. Methods Women consecutively diagnosed as having ASC-US were included in a prospective study, and underwent colposcopy and collection of cervico-vaginal cells for conventional Pap test and HPV test (Hybrid Capture 2, High-risk probe set, Digene). Repetition of all three tests was scheduled for 12 months later. DNA was subsequently extracted from residual cells of positive samples, and analysed by polymerase chain reaction with several primers for typing of HPV sequences. Sensitivity, specificity and positive predictive value (PPV) of the different triage options for histology-confirmed cervical intraepithelial neoplasia, grade 2 or worse (CIN2+) were calculated among all women and by age (under and above 35 years). Results Seven hundred forty-nine women 25–64 years old (median age 42 years) were enrolled in the study. Pap smears at enrolment were read as ASC-US or more severe in 211 (29.4%) cases, colposcopy disclosed an atypical transformation zone in 254 (34.2%) women, and HPV test was positive in 181 (24.2%). High-grade cervical lesions developed in 29/749 (3.9%) women. HPV typing was possible in 163 (90%) of the samples, and carcinogenic types were present in 123. Conclusions HPV test showed the best performance; overall, it had the highest sensitivity (92.3%), specificity (78.6%) and PPV (14.9%).

For Detecting CIN, Cytology Method Might Not Matter

Studies designed to compare liquid-based cytology and conventional Pap tests have yielded disparate results. To investigate this discrepancy, Dutch

Comparison of Liquid-Based Cytology With Conventional Cytology for Detection of Cervical Cancer Precursors

Liquid-based cytology has been developed as an alternative for conventional cervical cytology. Despite numerous studies and systematic reviews, controversy remains about its diagnostic accuracy. To assess the performance of liquid-based cytology compared with conventional cytology in terms of detection of histologically confirmed cervical intraepithelial neoplasia (CIN). Cluster randomized controlled trial involving 89,784 women aged 30 to 60 years participating in the Dutch cervical screening program at 246 family practices. One hundred twenty-two practices were assigned to use liquid-based cytology and screened 49,222 patients and 124 practices were assigned to use the conventional Papanicolaou (Pap) test and screened 40,562 patients between April 2004 and July 1, 2006. Patients were followed up for 18 months through January 31, 2008. Screening for CIN using liquid-based cytology or conventional papanicolaou (Pap) test and the blinded review of all follow-up of screen-positive women (blinded to the type of cytology and the initial result). Intention-to-treat and per-protocol analysis of the detection rates of and positive predictive values for histologically verified CIN in both cytology systems. Outcomes are presented as crude and adjusted rate ratios (adjustment for age, urbanization, study site, and period). The adjusted detection rate ratios for CIN grade 1+ was 1.01 (95% confidence interval [CI], 0.85-1.19); for CIN grade 2+, 1.00 (95% CI, 0.84-1.20); for CIN grade 3+, 1.05 (95% CI, 0.86-1.29); and for carcinoma, 1.69 (95% CI, 0.96-2.99). The adjusted positive predictive value (PPV) ratios, considered at several cytological cutoffs and for various outcomes of CIN did not differ significantly from unity. This study indicates that liquid-based cytology does not perform better than conventional Pap tests in terms of relative sensitivity and PPV for detection of cervical cancer precursors. trialregister.nl Identifier: NTR1032.

Screening and Treating Cervical Cancer in HIV-Positive Women in Cambodia

Screening and Treating Cervical Cancer in HIV-Positive Women in Cambodia

Diagnostic accuracy of conventional Pap test, liquid-based cytology and human papillomavirus DNA testing in cervical cancer screening in Korea: a meta-analysis.

Screening is the main strategy for secondary prevention of uterine cervical cancer. Cytological screening, Pap test, has led to a significant reduction in the incidence of and mortality from cervical cancer[1]. Conventional Pap test was introduced into Korea in the late 1950’s and has contributed to early detection of precancerous lesions and cervical cancer. Korean National Cancer Screening Program recommends that women of age 30 or more receive the Pap test biannually, whereas the Korean Society of Obstetrics and Gynecology recommends that women of age 20 or more receive the test annually[2]. Although Pap test has the merit of being convenient, reasonably specific and inexpensive, the sensitivity have been questioned. A low sensitivity of Pap test would put women at risk to develop invasive cervical cancer. Considerable variation in the sensitivity and specificity of Pap test has been reported[3]. In attempt to improve sample quality, interest has shifted to use liquid-based cytology (LBC). Although not included as a screening method in Korea, LBC has been rapidly popular among clinicians. In view of the importance of human papillomavirus (HPV) in the etiology of cervical cancer, HPV DNA testing to allow women to be classified as high-risk HPV-positive or negative could be used as an adjunct to Pap test. Currently there is no recommendation for HPV testing in cervical cancer screening guidelines. However, the National Health Insurance Corporation has approved HPV testing to confirm cervical dysplasia or carcinoma resulting from an abnormal Pap. Estimations sensitivity and specificity of screening test are important because they may be used to determine policy decisions, such as recommendations for optimal frequency of screening, management of mild abnormalities, and use of newer methods. To compare the accuracy of Pap test and other alternative screening tools (i.e., LBC and HPV testing), Korean studies that reported accuracy of each screening methods were intensively reviewed and the pooled estimates for sensitivity and specificity was calculated by meta-analysis.

Value of Conventional Pap Smear, Liquid-Based Cytology, Visual Inspection and Human Papillomavirus Testing as Optional Screening Tools Among Latin American Women < 35 and = 35 Years of Age

To compare performance of conventional Pap test, liquid based cytology (LBC) and visual inspection with acetic acid (VIA), as well as human papillomavirus (HPV) testing in 2 subcohorts of women, <35 and > or =35 years of age.Performance indicators were calculated using colposcopic biopsies as the gold standard; all results were corrected for verification bias using maximum likelihood.Both conventional Pap test n d Hybrid Capture 2 (HC2) assay performed significantly better among older women than younger; no difference was observed in performance of LBC and VIA, both inferior to Pap and HC2. The Pap test was more specific than HC2 in both subcohorts; HC2 had the highest sensitivity. For individual tests, the best balance between sensitivity and specificity was obtained for HC2 assay corrected for verification bias in the older women's subcohort; this was further improved by the combined use of the Pap test and HC2.Age of the target population is an important determinant of the performance of different screening tests. The choice of optimal test for women <35 and > or =35 years of age depends on whether the highest positive predictive value (Pap test).

Comparison of Carnoy’s Solution and 96% Ethyl Alcohol Fixation in Bloody Pap Smears

To compare 2 methods of fixation in bloody Pap smears with Carnoy's solution and 96% ethyl alcohol.After observation of contact bleeding, 2 samples were prepared from cervical cells with conventional Pap smear. One sample was fixed in 96% ethyl alcohol and another sample was fixed in Carnoy's solution.Of 450 slides, 410 were selected for study. In study of cell adequacy, diagnosis of squamous cells and glandular cells was better in Carnoy's-fixed slides. Blood contamination of slides was reduced in Carnoy's-fixed slides (13.85% vs. 49.51%), and clearance of slides was increased in Carnoy's-fixed slides. Diagnosis of inflammatory cells and pathogenic microorganisms in was increased in Carnoy's-fixed slides, but no difference was seen in diagnosis of epithelial cell and glandular cell abnormalities.Carnoy's solution can be used as an effective fixative in bloody smears in conventional Pap tests.

Liquid Compared With Conventional Cervical Cytology

To compare test performance characteristics of conventional Pap tests and liquid-based cervical cytology samples. Eligible studies, published between 1991 and 2007, were retrieved through PubMed/EmBase searching and completed by consultation of other sources. Studies were selected if a conventional and a liquid-based sample were prepared from the same woman or when one or the other type of sample was taken from a separate but similar cohort. The current systematic review and meta-analysis is restricted to studies where all subjects were submitted to gold standard verification, based on colposcopy and histology of colposcopy-targeted biopsies, allowing computation of absolute and relative test validity for cervical intraepithelial neoplasia grade 2 or worse. Randomized trials were selected as well if all test-positive cases were verified with the same gold standard, allowing computation of the relative sensitivity. Impact of study characteristics on accuracy was assessed by subgroup meta-analyses, meta-regression, and summary receiver operating characteristic curve regression. The relative sensitivity, pooled from eight studies, with complete gold standard verification and from one randomized clinical trial, did not differ significantly from unity. Also, the specificity, considering high-grade and low-grade squamous intraepithelial lesions as cutoff, was similar in conventional and liquid cytology. However, a lower pooled specificity was found for liquid-based cytology when presence of atypical squamous cells of undetermined significance was the cutoff (ratio 0.91, 95% confidence interval 0.84-0.98). Differences in study characteristics did not explain interstudy heterogeneity. Liquid-based cervical cytology is neither more sensitive nor more specific for detection of high-grade cervical intraepithelial neoplasia compared with the conventional Pap test.

The impact of new technologies in cervical cancer screening: Results of the recruitment phase of a large randomised controlled trial from a public health perspective

The decision to introduce liquid-based cytology (LBC) and HPV as screening tests involves criteria based on resource consumption. We used cross-sectional data at recruitment from the NTCC trial [ISRCTN81678807] on 28,000 women aged 35-60, randomised to receive a conventional Pap test or LBC plus HPV. We computed the resources employed to detect a CIN2+ with different screening strategies. In order to result in the same overall cost per CIN2+ detected as screening by conventional cytology, the unit cost of LBC used alone should be less than that of a conventional Pap while its unit cost may be up to 20% higher if HPV-triage for Atypical Squamous Cells of Undetermined Significance is applied together. With the same criterion the unit cost of HPV used alone may be about 20% higher than that of a Pap-test using a 1 pg/ml cut-off and over 40% higher using a 10 pg/ml cut-off. If HPV testing is applied with cytology-triage, a single HPV test may cost 20-30% more than a conventional Pap to result in the same overall cost per CIN2+ detected.