Cervical Human Papillomavirus Testing With Two Home Self-Collection Methods Compared With a Standard Clinically Collected Sampling Method.

BACKGROUND: The purpose of this study was to compare the outcomes of 2 self-collection methods to detect cervical human papillomavirus (HPV) DNA with outcomes from a standard clinical method. The standard method samples were collected by a clinician at a routine pelvic examination. Self-samples were taken at home and mailed to the clinical laboratory. METHODS: The 2 self-collection methods were a tampon-based method and a swab-based method using a commercial device, an Eve Medical HerSwab. All HPV samples were processed by a clinical laboratory using the Food and Drugs Administration approved Roche Cobase HPV method, which specifically identifies HPV 16, HPV 18, and a set of 12 other high-risk subtypes. Patients were recruited from 2 cancer screening clinics 2015 to 2017. All patients signed an informed consent. Screening outcomes, such as prevalence, percent agreement with standard, sensitivity, and specificity, were calculated for each self-collection method. Measures of similarity between self and standard collection outcomes, Cohen's κ, percent concordance, McNemar equivalence, and others were tested statistically. RESULTS: One hundred seventy-four patients were randomized. The prevalence of 1 or more positive HPV high-risk subtypes from the standard clinical specimens was 13.5%. All clinical specimens were sufficient for valid HPV detection. For the tampon method, 15 (27%) of the specimens were insufficient quality. Only 1 (2%) swab specimen was insufficient. Only the swab self-collection method was found to be statistically noninferior to the clinical method. The tampon method had an unacceptably high rate of insufficient quality specimens and also failed the equivalency tests. CONCLUSIONS: The swab home collection samples were equivalent to the clinical samples, but the tampon method had an unacceptably high rate of specimens insufficient for HPV detection.

Validation of a new HPV self-sampling device for cervical cancer screening: The Cervical and Self-Sample In Screening (CASSIS) study.

OBJECTIVE: We compared the self-sampling performance of the newly designed HerSwab™ device with a physician-collected cervical sample and another self-sample using the cobas® PCR Female swab for the detection of cervical intraepithelial neoplasia (CIN) and cancer. METHODS: Women referred for colposcopy at McGill University affiliated hospital clinics collected two consecutive self-samples, one with HerSwab™ and one with cobas® swab, after receiving instructions. The order of sampling was randomized. The colposcopist then collected a cervical sample and conducted a colposcopic examination. Samples were tested for human papillomavirus (HPV) DNA. Sensitivity and specificity to detect CIN2+ and respective 95% confidence intervals (CI) were calculated to compare sampling approaches. The HPV testing agreement between samples was measured using the Kappa statistic. RESULTS: Of 1217 women enrolled, 1076 had complete results for HPV and cytology; 148 (13.8%) had CIN1, 147 (13.7%) had CIN2/3, and 5 (0.5%) had cancer. There was very good agreement between methods for HPV detection (HerSwab™ versus physician: kappa=0.84; cobas® swabs versus physician: kappa=0.81; HerSwab™ versus cobas® swabs: kappa=0.87). The sensitivity of HPV detection for CIN2+ was 87.6% (95%CI: 79.8-93.2) with self-sampling using HerSwab™, 88.6% (95%CI: 80.9-94.0) with self-sampling using the cobas® swab, and 92.4% (95%CI: 85.5-96.7) with physician sampling. Corresponding estimates of specificity were 58.1% (95%CI: 54.1-62.1), 55.0% (95%CI: 50.9-59.0) and 58.7% (95%CI: 54.6-62.6). Cytology (ASC-US or more severe) done on the physician-collected specimen was 80.2% (95%CI: 70.8-87.6) sensitive and 61.4% (95%CI: 57.2-65.5) specific for CIN2+. CONCLUSIONS: The HerSwab™ had good agreement with physician sampling in detecting HPV, and adequate performance in detecting high-grade lesions among women referred to colposcopy for abnormal cytology.

Implementation of a real-time reference and calibration grid platform for improved screening - mapping in Pap test slides.

Cervical cancer screening based on the Papanicolaou (Pap) test is a widely applied but not always efficient practice for detecting Human Papillomavirus (HPV) mediated lesions, partially due to a non-systematic and inadequate screening process. Our aim was to introduce an inexpensive easy-to-use direct screening platform for improved detection of abnormal cells indicative of underlying cervical neoplasia as well as persisting HPV infection. By employing a novel, efficient technique of laser-based micromachining, we achieved the fabrication of spatial grids on commercially available coverslips allowing visual segmentation of the slide for efficient screening. Abnormal and formerly diagnosed as negative for intraepithelial lesion or malignancy (NILM) Pap test slides (n = 200) were analyzed by conventional and grid-based screening. Grid-based microscopy led to a more reliable diagnosis compared to the conventional by identifying an increased number of abnormal cells (P = 0.001). It decreased borderline ASCUS, AGC diagnosis, increasing LSIL, HSIL and in situ AdenoCa detection rates closely related with biopsy (P = 0.015; kappa = 0.978). Concerning the set of NILM diagnoses in rapid re-screening, the method upgraded six cases (n = 6) to LSIL (P = 0.001). The proposed technical solution offers a calibration and orientation visual aid during the on-site screening process providing significant advantages compared to expensive digital imaging techniques.

Accuracy of self-collected human papillomavirus samples from Japanese women with abnormal cervical cytology.

AIM: The aim of this study was to assess the accuracy of self-collected vaginal samples compared with physician-collected cervical samples for high-risk human papillomavirus (HPV) testing in Japanese women with abnormal cervical cytology. We also assessed the acceptability of self-collected HPV (sHPV) testing using a questionnaire. METHODS: Women aged 20-69 years (n = 136) attending Yokohama City University Hospital because of abnormal cervical cytology between April 2014 and January 2015 were enrolled in this study. Cervical samples for conventional cytology and physician-collected HPV (pHPV) testing were obtained before colposcopic examination. After this examination, patients were asked to provide a self-sampled vaginal specimen (sHPV) at home, some time between the following day and the next week and to complete a self-sampling acceptability questionnaire. RESULTS: The overall positive rates of HPV detection with pHPV and sHPV testing were 61.0% (83/136) and 40.4% (55/136), respectively (P < 0.001). sHPV testing had a lower sensitivity compared to pHPV for detection of cervical intraepithelial neoplasia (CIN)2 or worse (CIN2+: 59.4% vs 100%, P < 0.001; CIN3: 66.7% vs 100%, P = 0.248). There were no statistically significant differences in the sensitivity to detect CIN3 among pHPV testing, sHPV testing, and cytology. The self-collecting device had good acceptability. CONCLUSION: sHPV testing is a possible technique with which to improve poor cervical cancer screening uptake rates in Japan; however, the sensitivity to detect CIN2+ lesions must improve before it can be a substitute for conventional cytology or pHPV testing. Further large-scale acceptability studies involving non-responders are also needed before practical application.

Self-sampling to increase participation in cervical cancer screening: an RCT comparing home mailing, distribution in pharmacies, and recall letter.

BACKGROUND: We performed a multicentre randomised controlled trial to evaluate the effect on participation in organised screening programmes of a self-sampling device mailed home or picked up at a pharmacy compared with the standard recall letter. METHODS: Women aged 30-64 non-responding to screening invitation were eligible. Response rate to first invitation ranged from 30% to 60% between centres. The control was the standard reminder letter to undergo the test used by the programme (Pap test in three centres and HPV DNA test in three other centres). Home mailing of the self-sampler was preceded by a letter with a leaflet about HPV. The analysis was intention-to-treat. RESULTS: In all, 14 041 women were randomised and recruited: 5012 in the control arm, 4516 to receive the self-sampler at home, and 4513 to pick up the self-sampler at a pharmacy. Participation was 11.9% in the control, 21.6% (relative participation: 1.75; 95% CI 1.60-1.93) in home, and 12.0% (relative participation: 0.96; 95% CI 0.86-1.07) in the pharmacy arms, respectively. The heterogeneity between centres was high (excess heterogeneity of that expected due to chance, i.e., I(2), 94.9% and 94.1% for home and pharmacy arm, respectively). The estimated impact on the overall coverage was +4.3% for home mail self-sampling compared with +2.2% for standard reminder. CONCLUSIONS: Home mailing of self-sampler proved to be an effective way to increase participation in screening programmes, even in those with HPV as primary testing. Picking up at pharmacies showed effects varying from centre to centre.

Cost-effectiveness of using the Cervex-Brush (broom) compared to the elongated spatula for collection of conventional cervical cytology samples within a high-burden HIV setting: a model-based analysis.

BACKGROUND: From 2010 to 2014, approximately 2 million Pap smears from HIV-infected women were submitted to the South African National Health Laboratory Services (NHLS) through the national cervical cancer screening programme. The objective of this analysis was to determine whether using the plastic Cervex brush ("broom") would be a cost-effective approach to improve cytology specimen quality as compared to the wooden spatula used currently. METHODS: A decision analysis model was built using the expected adequacy rates for samples collected with the spatula (<$0.02) and broom ($0.23) and the probability of detecting cervical dysplasia. NHLS data was used for testing volumes and rates of HIV-positivity, suitability of specimens, and presence of endocervical cells. Expected positivity of Pap smears in HIV-infected women (73 %), odds ratios of the effectiveness of the broom (OR: 1.57), and improved sensitivity when endocervical cells present (OR: 1.89) are from literature. NHLS costs were used for the collection devices and conventional cytology ($4.89). Cost of clinic visit is from WHO CHOICE ($8.36). RESULTS: In 2010, 80 % of specimens submitted to NHLS were adequate for evaluation; in 2014, only 54 % met the same criteria. For HIV-infected women, according to the guidelines model, using the wooden spatula costs $6.25 million per year, $16.79 per woman tested. Under intended practice, for each additional HSIL case detected among HIV-infected women, the South African cervical cancer screening programme could save $13.64 (95 % CI: $13.52 to $13.76) by using the broom as its standard of care collection device through increased collection of endocervical cells and consequent reduction in repeat Pap smears. CONCLUSION: Under a wide range of parameters tested using a simulation model, the more expensive plastic broom could save the South African cervical cancer screening programme money and increase detection of high-grade cervical dysplasia in HIV-infected women compared to the current wooden spatula.

Evaluation of a New Automated Processing System (TACAS™ Pro) for Liquid-Based Procedures.

OBJECTIVE: To evaluate a fully automated processing system (TACAS™ Pro) for liquid-based procedures (LBPs). METHODS AND MATERIALS: Materials were 3,483 and additionally 502 specimens that were taken at Kanagawa Health Service Association. Specimens obtained with a Cervex-Brush® were first smeared to glass slides using one side of the brush and then processed to TACAS Pro. RESULTS: (1) The microscopy watching time per normal case was 3.65 ± 0.85 min in the conventional procedure, whereas in the LBP it was 1.95 ± 0.60 min, and the latter reduced workload to 53%. (2) The handling time of TACAS Pro per day was 2 h and 25.8 min. The workload at a laboratory offset it and revealed the work saving to be 63.8%. (3) Unsatisfactory rates were 0% in the conventional procedure, whereas in the LBP it was 1.88% at first. The latter rate decreased to 0.5% after system improvement. (4) Specimens which may disturb microscopy analysis were found in 1.06%, including 3 cases of possible carry-over of cells to the following slides. An additional study with the revised system confirmed no carry-over. (5) Incidences of abnormal cytology were consistent between the two methods. CONCLUSIONS: The revised automated processing system TACAS Pro is a feasible and useful LBP and reduces the workload of cytology laboratories.

The role of gel application in decreasing pain during speculum examination and its effects on papanicolaou smear results.

PURPOSE: This study aimed to investigate the effects of water-based gel application in reducing pain or discomfort associated with speculum examination, and compared the presence of unsatisfactory Papanicolaou smear results between gel-applied and control groups. METHODS: In this prospective randomized controlled study, a total of 1,580 patients were analyzed. The subjects were randomized to a gel group and a control group. For the collection of the smear sample, water-based gel was used in the gel group and dry speculum was used in the control group. All patients were asked to score their pain on a numeric pain scale at two time points during the procedure (insertion and opening phase of speculum). Cytopathologists who analyzed the smear cytology were blinded to the study. Pain intensity during speculum examination, as well as unsatisfactory smear results, were analyzed between the groups. RESULTS: The pain scores obtained at two different time points of speculum application were significantly lower in the gel group compared to the control group both in premenopausal and postmenopausal women (p < 0.001). The ratios of unsatisfactory cytopathologic examination results were 1.13 and 1.39% for the gel-applied and control groups, which were not significantly different. CONCLUSION: Lubrication of the outer superior and inferior blade of the plastic vaginal speculum with a small amount of a water-soluble lubricant gel decreases the pain associated with insertion and opening of the vaginal speculum in both premenopausal and postmenopausal women without affecting the quality of the cytology results during the collection of Papanicolaou test specimens.

The Peru Cervical Cancer Prevention Study (PERCAPS): the technology to make screening accessible.

OBJECTIVE: This study utilized a combination of HPV self-sampling, iFTA elute specimen cards, and long distance transport for centralized processing of specimens to determine the feasibility of large-scale screening in remote and transient populations. METHODS: This study was performed in two locations in Peru (Manchay and Iquitos). The "Just For Me" cervico-vaginal brush and iFTA elute cards were used for the collection and transport of specimens. Samples were shipped via FedEx to China and tested for 14 types of high-risk HPV using PCR based MALDI-TOF. HPV positive women were treated with cryotherapy after VIA triage, and followed-up with colposcopy, biopsy, ECC, and repeat HPV testing at 6 months. RESULTS: Six hundred and forty three women registered, and 632 returned a sample over a 10 day period. Within 2 weeks, specimens were shipped, samples tested, and results received by study staff. Sixty-eight women (10.8%) tested positive, and these results were delivered over 4 days. Fifty-nine HPV positive women (87%) returned for evaluation and treatment, and 2 had large lesions not suitable for cryotherapy. At 6 months, 42 women (74%) returned for follow-up, and 3 had CIN 2 (all positive samples from the endocervical canal). Ninety eight percent of participants reported that they would participate in this type of program again. CONCLUSIONS: Utilizing HPV self-sampling, solid media specimen cards for long distance transport, and centralized high throughput processing, we achieved rapid delivery of results, high satisfaction levels, and low loss to follow-up for cervical cancer screening in remote and transient populations.

A second generation cervico-vaginal lavage device shows similar performance as its preceding version with respect to DNA yield and HPV DNA results.

BACKGROUND: Attendance rates of cervical screening programs can be increased by offering HPV self-sampling to non-attendees. Acceptability, DNA yield, lavage volumes and choice of hrHPV test can influence effectiveness of the self-sampling procedures and could therefore play a role in recruiting non-attendees. To increase user-friendliness, a frequently used lavage sampler was modified. In this study, we compared this second generation lavage device with the first generation device within similar birth cohorts. METHODS: Within a large self-sampling cohort-study among non-responders of the Dutch cervical screening program, a subset of 2,644 women received a second generation self-sampling lavage device, while 11,977 women, matched for age and ZIP-code, received the first generation model. The second generation device was different in shape, color, lavage volume, and packaging, in comparison to its first generation model. The Cochran's test was used to compare both devices for hrHPV positivity rate and response rate. To correct for possible heterogeneity between age and ZIP codes in both groups the Breslow-Day test of homogeneity was used. A T-test was utilized to compare DNA yields of the obtained material in both groups. RESULTS: Median DNA yields were 90.4 µg/ml (95% CI 83.2-97.5) and 91.1 µg/ml (95% CI 77.8-104.4, p= 0.726) and hrHPV positivity rates were 8.2% and 6.9% (p= 0.419) per sample self-collected by the second - and the first generation of the device (p= 0.726), respectively. In addition, response rates were comparable for the two models (35.4% versus 34.4%, p= 0.654). CONCLUSIONS: Replacing the first generation self-sampling device by an ergonomically improved, second generation device resulted in equal DNA yields, comparable hrHPV positivity rates and similar response rates. Therefore, it can be concluded that the clinical performance of the first and second generation models are similar. Moreover, participation of non-attendees in cervical cancer screening is probably not predominantly determined by the type of self-collection device.

Translational approaches to improving cervical screening.

Screening programmes for cervical cancer using the current test--the Pap smear--have markedly reduced the incidence of the disease. However, an individual Pap test is of limited sensitivity and is difficult and expensive to perform. Increased understanding of the molecular pathogenesis of cervical cancer indicates that new approaches to screening might offer increased accuracy, affordability and the potential for automation. Such approaches exemplify how improved understanding of the biology of neoplasia might be translated into clinical benefit.

Effects on cervical cytology screening productivity associated with implementation of the BD FocalPoint™ Guided Screener Imaging System.

OBJECTIVES: Automated screening will become important due to an aging workforce, declining numbers of new cytotechnologists, and the need for increased screening sensitivity in the vaccine era, where high-grade abnormalities will decline. This study documents workload in gynecologic cytology throughput before and after the implementation of the BD FocalPoint™ Guided Screener (GS) System. STUDY DESIGN: We collected daily screening data from 3 time periods: the 12 months prior to GS implementation, the 6 months immediately after implementation, and the ensuing 7-18 months after implementation. Data was tabulated at the individual and total laboratory levels. RESULTS: In the 6-month period immediately following implementation, productivity increased in 3 of 5 cytotechnologists, as compared to the figures 12 months before implementation. The laboratory increased productivity slightly (+2.4%), with individual changes ranging from -6.9 to +14.7%. In the 7- to 18-month 'mature' period after implementation, productivity increased in all 5 cytotechnologists with an average of +15.4%. Individual increases ranged from +6.1 to +26.9%. CONCLUSIONS: Overall productivity increased in the period beyond 6 months, and this increase was eventually noted in all personnel. Increased productivity was associated with a short period of learning in which the magnitude of the effect was less than in the mature period.

Optimal sampling devices for liquid-based procedure in screening for cervical cancer: comparison between cotton stick/Cytobrush and Cervex-Brush.

OBJECTIVE: To find an appropriate sampling device for a liquid-based procedure in the population screening for cervical cancer, focusing on bleeding at sampling and the amount of cells smeared. METHODS AND MATERIALS: 1,000 consecutive women who underwent primary screening were studied. The specimens were obtained with the cotton stick/Cytobrush® method in the first 500 cases or with the Cervex-Brush® in the following 500 subjects, and were processed using the Thinlayer Advanced Cytology Assay System (TACAS™) following the manufacturer's instructions. RESULTS: (1) Bleeding at cellular sampling using the cotton stick/Cytobrush and Cervex-Brush methods occurred in 1.2 and 8.8% of the cases, respectively (p < 0.0001). (2) The incidences of cells obtained with the two methods which covered the whole area, <1/2 and ≥1/4, and <1/4 of the observation fields were 55.4 versus 62.2% (p < 0.05), 14.6 versus 9.4% (p < 0.05), and 2.0 versus 4.0% (p < 0.05), respectively. (3) The incidences of endocervical or metaplastic cells obtained with ≥500 and <10 were 34.6 versus 20.0% (p < 0.01) and 9.4 versus 18.4% (p < 0.01), respectively. In cases of cells covering <1/4, incidences with <10 were 0 and 0.6% (n = 3), respectively. (4) Detection rates of abnormal cytology were 3.4 and 5.2% (n.s.), including atypical squamous cells of undetermined significance in 2.4 and 3.2%. CONCLUSIONS: The cotton stick/Cytobrush is superior to the Cervex-Brush as a cellular sampling device for the TACAS liquid-based procedure.

Performance of the CellSolutions Glucyte liquid-based cytology in comparison with the ThinPrep and SurePath methods.

OBJECTIVE: Glucyte liquid-based cytology (LBC; BestPrep™;CellSolutions, LLC, Greensboro, N.C., USA) is a recently developed method. Its performance was assessed in comparison with ThinPrep (Hologic Inc., Marlborough, Mass., USA) and SurePath (BD Diagnostics, Burlington, N.C., USA) LBC platforms. STUDY DESIGN: Two cervical samples obtained from each of 331 patients presenting for colposcopy were utilized. The first sample was placed in PreservCyt (Hologic) and the second in SurePath medium, and both were processed in accordance with the manufacturers' protocols. From the residual SurePath sample, a Glucyte slide was prepared, stained, and read as per the manufacturer's instructions. RESULTS: Considering a threshold cytologic diagnosis of atypical squamous cells of undetermined significance and using a histologic diagnosis of high-grade cervical intraepithelial neoplasia or worse (CIN 2+) as the end point, there was no significant difference in the sensitivity of Glucyte for the detection of CIN 2+ compared with ThinPrep and SurePath (86.9 vs. 81.9% and 83.7%, respectively). However, Glucyte showed a specificity of 49.2% compared with 61.6% for ThinPrep (p = 0.002) and 66.9% for SurePath (p < 0.001). Considering a threshold cytologic diagnosis of high-grade squamous intraepithelial lesion, Glucyte showed a sensitivity of 40.5% for detecting CIN 2+ compared with 20.5% for ThinPrep (p = 0.003) and 54.7% for SurePath (p = 0.013). The corresponding specificities were 93.8, 99.1, and 94.3%. The rate of unsatisfactory specimens for Glucyte was 1.2% compared with ThinPrep (4.8%) and SurePath (0%). CONCLUSION: Glucyte appeared to perform reasonably well compared with ThinPrep and SurePath. It offers an alternative to these well recognized LBC systems.

Effectiveness of the ThinPrep Imaging System in the detection of abnormal cervicovaginal cytology: a practical experience in Korea.

OBJECTIVE: The purpose of this study is to report our experience with the implementation of the ThinPrep Imaging System (TIS) in a tertiary hospital in Korea and to evaluate the effectiveness of the TIS compared to manual methods in the screening of cervical cytology. STUDY DESIGN: Detection rates of cervical abnormalities in the pre- and post-TIS periods (January 2009 to February 2010 and March 2010 to December 2010, respectively) were compared. Follow-up cytological and histological results with concurrent or subsequent human papillomavirus (HPV) tests were retrieved. RESULTS: ASC-US, ASC-H, LSIL, and HSIL were more frequently detected in the post-TIS period than in the pre-TIS period (p < 0.005). The proportions of correlated cases of ASC-US were 42.2 and 40.4% in the pre- and post-TIS periods, respectively. The detection rates of high-risk types of HPV in ASC-US were not significantly different between the two groups. The proportion of correlated biopsy for ASC-H, LSIL, and HSIL was similar in both periods. HPV positivity for ASC-H, LSIL, and HSIL showed no significant change between the two periods. CONCLUSION: The TIS is potentially useful for the detection of abnormal cervical cytology on the basis of the increased detection rate of squamous cell abnormalities, with a relatively similar proportion of correlated cases compared to the manual screening method.

[Self-collection of test material. Supplement to cervical cancer screening]. / Selbstentnahme von Untersuchungsmaterial. Ergänzung beim Zervixkarzinomscreening.

BACKGROUND: Recent studies have reported high sensitivity of human papillomavirus (HPV) testing from self-collected vaginal specimens. These results suggest the possibility of introducing self-collection of samples for cervical cancer screening to increase overall participation. The current study compared test results from self-collected and physician-collected specimens. PATIENTS AND METHODS: Vaginal samples from patients (n = 102) of a colposcopy clinic were taken by both a physician and themselves. All cell samples were tested using cytological diagnostics with a PAP test and for carcinogenic HPV genotypes (Cervista®). Additionally, all patients had a colposcopy (86% with cervical biopsy) and in 40% of patients was carried out a conisation. RESULTS: Of the patients tested 50 had the histological diagnosis of a cervical intraepithelial neoplasia grade 2 (CIN 2+ or 3). Sensitivity of HPV self-collected samples was much lower than that of physician-collected samples (72 % compared to 92 %). The sensitivity of self-collected PAP tests was only 52 % but the positive predictive value of self-collected PAP tests was very high. The cytological diagnosis of high-grade intraepithelial lesion (HSIL) correlated much better with the histological results of conisation (96 %) than with cervical biopsies (76 %). CONCLUSION: The results of this study indicate that self-collection may not provide an adequate collection method for improving efficiency in cervical cancer screening in Germany.

In vitro validation of vaginal sampling in rape victims: the problem of Locard's principle.

PURPOSE: Intra-vaginal traces can serve as supporting physical evidence of vaginal penetration in sex-crime cases. Vaginal trace sampling guidelines prescribe using a speculum and swabs or swabs only. The use of Locard's exchange theory requires samples of trace materials to always be contamination-free and of accurately known origin. If traces from the outer genital area are accidentally introduced into the vagina during sampling, these traces may be recorded as originating in a location where they were not present at the time of evidence collection. The goal of this study was to assess the risks of false positive findings in vitro of traces found inside the vagina due to trace dislocation caused by current vaginal trace sampling methods (swab-only or with speculum), and for a new method that uses a sleeve accessory to prevent trace dislocation. METHODS: Starch solution was applied to the labia of three clean female genitalia mock-ups with vaginas of various diameters and structures. The speculum, swab-only, and sleeve methods were each used 30 times on each mock-up, giving a total of 90 repetitions of each method. Iodine was used to determine whether any starch traces had been introduced vaginally. RESULTS: The speculum and swab-only methods gave 100 and 63-87 % false positive results respectively due to trace dislocation. The sleeve method reduced this to 2 % (0 % after correction). CONCLUSIONS: The results suggest that there is a need to conduct clinical in vivo studies to determine whether these results translate into everyday practice and to ensure reliable trace sampling in sex-crime cases.

Improved sensitivity of vaginal self-collection and high-risk human papillomavirus testing.

Self-collected vaginal specimens tested for high-risk human papillomavirus (HR-HPV) have been shown to be less sensitive for the detection of cervical intraepithelial neoplasia or cancer (≥CIN 3) than physician-collected endocervical specimens. To increase the sensitivity of self-collected specimens, we studied a self-sampling device designed to obtain a larger specimen from the upper vagina (POI/NIH self-sampler) and a more sensitive polymerase chain reaction (PCR)-based HR-HPV assay. Women (10,000) were screened with cervical cytology and HR-HPV testing of vaginal self-collected and endocervical physician-collected specimens. Women were randomly assigned to use either a novel self-collection device (POI/NIH self-sampler) or conical-shaped brush (Qiagen). The self-collected and clinician-collected specimens were assayed by Cervista (Hologic) and the research only PCR-based matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF). Women with any abnormal screening test underwent colposcopy and biopsy. Women (8,556), mean age of 38.9, had complete data; 1.6% had ≥ CIN 3. For either HR-HPV assay, the sensitivity was similar for the two self-collection devices. Tested with Cervista, the sensitivity for ≥CIN 3 of self-collected specimens was 70.9% and for endocervical specimens was 95.0% (p = 0.0001). Tested with MALDI-TOF, the sensitivity for ≥CIN 3 of self-collected specimens was 94.3% and for endocervical specimens was also 94.3% (p = 1.0). A self-collected sample using a PCR-based assay with the capability of very high throughput has similar sensitivity as a direct endocervical specimen obtained by a physician. Large population-based screening "events" in low-resource settings could be achieved by promoting self-collection and centralized high-throughput, low-cost testing by PCR-based MALDI-TOF.

Cytology of the vulva: feasibility and preliminary results of a new brush.

OBJECTIVE: Taking a biopsy is a standard procedure to make the correct diagnosis in patients with suspicious premalignant vulvar lesions. The use of a less invasive diagnostic tool as triage instrument to determine whether biopsy is necessary may improve patient comfort especially in patients with chronic vulvar disorders that may warrant consecutive biopsies. This study was conducted to investigate whether vulvar brush cytology is feasible and may be used to detect (pre)malignant vulvar lesions. METHODS: A pilot study was performed with patients having clinically normal vulvar skin, lichen sclerosus (LS), usual or differentiated vulvar intraepithelial neoplasia or squamous cell carcinoma. A total of 65 smears were taken with the use of a vulvar brush and biopsies were performed for histopathological analysis. RESULTS: Out of 65 smears, 17 (26%) were discarded because of poor cellularity. A total of 28 of 29 (97%) smears with a histological proven (pre)malignancy had a smear classified as 'suspicious' or 'uncertain'. Cytology classified 11 smears as 'non-suspicious', of which 10 (91%) were indeed normal skin or LS. The accuracy, based on the presence of a lesion, for (pre)malignant lesions with the use of the brush showed a sensitivity of 97% and a negative predictive value of 88%. CONCLUSION: Vulvar brush cytology is feasible and may be a first step in the development of a triage instrument to determine whether subsequent biopsy of a clinically (pre)malignant lesion is necessary.

Detection of human papillomavirus among women in Laos: feasibility of using filter paper card and prevalence of high-risk types.

BACKGROUND: Persistent infection with high-risk (HR) human papillomavirus (HPV) is a well-recognized cause of cervical cancer, but little is known about the situation in Laos. The aims of the study were to determine the prevalence of HR-HPV among Lao women and to evaluate the use of a filter paper card (FTA Elute Micro Card) for collection of cervical cells in the humid tropical climate. METHODS: This is a cross-sectional study including 1922 women from 3 provinces in Laos. During a gynecological examination, cervical cells were collected and applied to the FTA card followed by HPV typing using a real-time polymerase chain reaction (PCR)-based assay. RESULTS: Overall, 213 of the 1922 women were positive for HR-HPV (11%). The most common type was the group HPV33/52/58 (3%), followed by the single type 16 (2%) and the group 18/45 (1%), respectively. Only 11 cards (0.6%) did not contain a sufficient amount of genomic DNA for polymerase chain reaction-based analysis. CONCLUSIONS: The prevalence of HR-HPV infections in Laos is similar to other Asian countries, and 40% of the women with an HR-HPV infection will be target of the present HPV vaccines. The FTA card is suitable for collection of cervical cells for HR-HPV typing in tropical conditions. This information is important for planning and establishing primary and secondary prevention of cervical cancer in Laos.