Background
Cervical cancer screening has traditionally been based on cervical cytology. Given the aetiological relationship between human papillomavirus (HPV) infection and cervical carcinogenesis, ...HPV testing has been proposed as an alternative screening test.
Objectives
To determine the diagnostic accuracy of HPV testing for detecting histologically confirmed cervical intraepithelial neoplasias (CIN) of grade 2 or worse (CIN 2+), including adenocarcinoma in situ, in women participating in primary cervical cancer screening; and how it compares to the accuracy of cytological testing (liquid‐based and conventional) at various thresholds.
Search methods
We performed a systematic literature search of articles in MEDLINE and Embase (1992 to November 2015) containing quantitative data and handsearched the reference lists of retrieved articles.
Selection criteria
We included comparative test accuracy studies if all women received both HPV testing and cervical cytology followed by verification of the disease status with the reference standard, if positive for at least one screening test. The studies had to include women participating in a cervical cancer screening programme who were not being followed up for previous cytological abnormalities.
Data collection and analysis
We completed a 2 x 2 table with the number of true positives (TP), false positives (FP), true negatives (TN), and false negatives for each screening test (HPV test and cytology) used in each study. We calculated the absolute and relative sensitivities and the specificities of the tests for the detection of CIN 2+ and CIN 3+ at various thresholds and computed sensitivity (TP/(TP + TN) and specificity (TN/ (TN + FP) for each test separately. Relative sensitivity and specificity of one test compared to another test were defined as sensitivity of test‐1 over sensitivity of test‐2 and specificity of test‐1 over specificity of test‐2, respectively. To assess bias in the studies, we used the Quality Assessment of Diagnostic test Accuracy Studies (QUADAS) tool. We used a bivariate random‐effects model for computing pooled accuracy estimates. This model takes into account the within‐ and between‐study variability and the intrinsic correlation between sensitivity and specificity.
Main results
We included a total of 40 studies in the review, with more than 140,000 women aged between 20 and 70 years old. Many studies were at low risk of bias. There were a sufficient number of included studies with adequate methodology to perform the following test comparisons: hybrid capture 2 (HC2) (1 pg/mL threshold) versus conventional cytology (CC) (atypical squamous cells of undetermined significance (ASCUS)+ and low‐grade squamous intraepithelial lesions (LSIL)+ thresholds) or liquid‐based cytology (LBC) (ASCUS+ and LSIL+ thresholds), other high‐risk HPV tests versus conventional cytology (ASCUS+ and LSIL+ thresholds) or LBC (ASCUS+ and LSIL+ thresholds). For CIN 2+, pooled sensitivity estimates for HC2, CC and LBC (ASCUS+) were 89.9%, 62.5% and 72.9%, respectively, and pooled specificity estimates were 89.9%, 96.6%, and 90.3%, respectively. The results did not differ by age of women (less than or greater than 30 years old), or in studies with verification bias. Accuracy of HC2 was, however, greater in European countries compared to other countries. The results for the sensitivity of the tests were heterogeneous ranging from 52% to 94% for LBC, and 61% to 100% for HC2. Overall, the quality of the evidence for the sensitivity of the tests was moderate, and high for the specificity.
The relative sensitivity of HC2 versus CC for CIN 2+ was 1.52 (95% CI: 1.24 to 1.86) and the relative specificity 0.94 (95% CI: 0.92 to 0.96), and versus LBC for CIN 2+ was 1.18 (95% CI: 1.10 to 1.26) and the relative specificity 0.96 (95% CI: 0.95 to 0.97). The relative sensitivity of HC2 versus CC for CIN 3+ was 1.46 (95% CI: 1.12 to 1.91) and the relative specificity 0.95 (95% CI: 0.93 to 0.97). The relative sensitivity of HC2 versus LBC for CIN 3+ was 1.17 (95% CI: 1.07 to 1.28) and the relative specificity 0.96 (95% CI: 0.95 to 0.97).
Authors' conclusions
Whilst HPV tests are less likely to miss cases of CIN 2+ and CIN 3+, these tests do lead to more unnecessary referrals. However, a negative HPV test is more reassuring than a negative cytological test, as the cytological test has a greater chance of being falsely negative, which could lead to delays in receiving the appropriate treatment. Evidence from prospective longitudinal studies is needed to establish the relative clinical implications of these tests.
To examine trends in the use of cervical cancer screening tests during 2013–2019 among commercially insured women.
The study population included women of all ages with continuous enrollment each year ...in the IBM MarketScan commercial or Medicare supplemental databases and without known history of cervical cancer or precancer (range = 6.9–9.8 million women per year). Annual cervical cancer screening test use was examined by three modalities: cytology alone, cytology plus HPV testing (cotesting), and HPV testing alone. Trends were assessed using 2-sided Poisson regression.
Use of cytology alone decreased from 34.2% in 2013 to 26.4% in 2019 among women aged 21–29 years (P < .0001). Among women aged 30–64 years, use of cytology alone decreased from 18.9% in 2013 to 8.6% in 2019 (P < .0001), whereas cotesting use increased from 14.9% in 2013 to 19.3% in 2019 (P < .0001). Annual test use for HPV testing alone was below 0.5% in all age groups throughout the study period. Annually, 8.7%–13.6% of women aged 18–20 years received cervical cancer screening. There were persistent differences in screening test use by metropolitan residence and census regions despite similar temporal trends.
Temporal changes in the use of cervical cancer screening tests among commercially insured women track changes in clinical guidelines. Screening test use among individuals younger than 21 years shows that many young women are inappropriately screened for cervical cancer.
•From 2013 to 2019, use of cytology alone decreased among women aged 21–64 years.•Use of cotesting increased among women aged 30–64 years.•There was little uptake of primary HPV screening among all age groups.•Many women younger than age 21 received cervical cancer screening which is not recommended.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Self-collection is comparable to current practice for detecting cervical lesions.•Collection devices may have impact on disease detection and on acceptability.•Delays in specimen preparation can ...notably affect the performance of self-collection.•Only validated procedure should be used and any delays should be minimized.
Comparative data on different self-collection methods is limited.
To assess the impact of hrHPV testing of two self-collection devices for detection of cervical carcinoma and high-grade lesions.
Three hundred ten patients collected two cervicovaginal specimens using a brush (Evalyn®Brush) and a swab (FLOQSwabs™), and filled a questionnaire at home. Then, a physician at the clinic took a cervical specimen into PreservCyt® buffer for hrHPV testing and cytology. All specimens were tested using Anyplex™ II HPV28, Cobas® 4800 HPV Test and Xpert®HPV.
Performance comparison included 45 cervical carcinomas and 187 patients with premalignant lesions. Compared to the physician-specimen, hrHPV testing of Evalyn®Brush showed non-inferior sensitivity for CIN3+ (relative sensitivity of Anyplex™ 0.99; Cobas® 0.96; Xpert®HPV 0.97) while hrHPV testing of FLOQSwabs™ showed inferior sensitivity (relative sensitivity of Anyplex™ 0.91; Cobas® 0.92; Xpert®HPV 0.93). Similar results were observed for invasive carcinomas albeit that FLOQSwabs™ was statistically non-inferior to the physician-specimen. Self-collection by either Evalyn®Brush or FLOQSwabs™ was more sensitive for CIN3+ than LSIL or worse cytology. Significant decrease in sensitivity for CIN3+ were observed for FLOQSwabs™ when specimens were preprocessed for hrHPV testing after 28 days. Both devices were well accepted, but patients considered Evalyn®Brush easier and more comfortable than FLOQSwabs™.
Self-collection is comparable to current screening practice for detecting cervical carcinoma and CIN3+ but device and specimen processing effects exist. Only validated procedure including collection device, hrHPV assay and specimen preparation should be used.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Microscopic evaluation of the types of cells present in vaginal smears has long been used to document the stages of the estrous cycle in laboratory rats and mice and as an index of the functional ...status of the hypothalamic–pituitary–ovarian axis. The estrous cycle is generally divided into the four stages of proestrus, estrus, metestrus, and diestrus. On cytological evaluation, these stages are defined by the absence, presence, or proportion of 4 basic cell types as well as by the cell density and arrangement of the cells on the slide. Multiple references regarding the cytology of the rat and mouse estrous cycle are available. Many contemporary references and studies, however, have relatively abbreviated definitions of the stages, are in reference to direct wet mount preparations, or lack comprehensive illustrations. This has led to ambiguity and, in some cases, a loss of appreciation for the encountered nuances of dividing a steadily moving cycle into 4 stages. The aim of this review is to provide a detailed description, discussion, and illustration of vaginal cytology of the rat and mouse estrous cycle as it appears on smears stained with metachromatic stains.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Data is needed about barriers to self-collection of Human Papillomavirus (HPV) samples and cytology among low-income, disadvantaged women living in rural areas of lower-income countries as these ...women are at increased risk of cervical cancer mortality.
Individual interviews (n = 29), focus groups (n = 7, 5-11 participants) and discussion groups (n = 2, 18-25 participants) were organized with women from three indigenous ethnic groups residing in rural areas in Mexico, after they were provided with free, self-sampled HPV tests. These groups are low-income, underserved by healthcare and have historically been on the receiving end of racism and social exclusion. Descriptive, qualitative content analysis was done, including two cycles of coding.
Interview and focus/discussion group data indicate women had limited understanding of HPV's role in cervical cancer etiology. They identified HPV's existence, that cytology detects cervical cancer, the need for regular testing and that cervical cancer is sexually transmitted. Organizational barriers to clinic-based cytology included irregular supplies of disposable speculums, distance to clinics and lack of clear communication by healthcare personnel. Women considered self-collected HPV-testing easy, less embarrassing and less painful than cytology, an opportunity for self-care and most felt they understood how to take a self-sample after a 20-min explanation. Some women feared hurting themselves when taking the self-sample or that they would take the sample incorrectly, which they worried would make the test useless. Attending HPV-testing in groups facilitated use by allowing women to discuss their doubts and fears before doing self-collection of the sample or to ask other women who were the first to do the self-sampling what the experience had been like (whether it hurt and how easy it was). Lack of indoor bathrooms was a barrier to doing HPV self-sampling at home, when those homes were resource-poor (one-room dwellings).
Low-income, indigenous Mexican women residing in rural, underserved areas identified their need for cervical cancer screening but encountered multiple barriers to cytology-based screening. They found a number of advantages of HPV self-sampled tests. Employing self-collected HPV-testing instead of cytology could resolve some but not all gender-related, organizational or technical quality-of-care issues within cervical cancer detection and control programs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The short reproductive cycle length observed in rodents, called the estrous cycle, makes them an ideal animal model for investigation of changes that occur during the reproductive cycle. Most of the ...data in the literature about the estrous cycle is obtained from rats because they are easily manipulated and they exhibit a clear and well-defined estrous cycle. However, the increased number of experiments using knockout mice requires identification of their estrous cycle as well, since (in)fertility issues may arise. In mice, like rats, the identification of the stage of estrous cycle is based on the proportion of cell types observed in the vaginal secretion. The aim of this unit is to provide guidelines for quickly and accurately determining estrous cycle phases in mice.
Abstract
We evaluated the accuracy of patient-collected skin lesions, oropharyngeal, and rectal swabs among 50 individuals enrolled in a study of mpox viral dynamics. We found that the performance of ...self-collected samples was similar to that of physician-collected samples, suggesting that self-sampling is a reliable strategy for diagnosing mpox.
IMPORTANCE: The number of deaths from cervical cancer in the United States has decreased substantially since the implementation of widespread cervical cancer screening and has declined from 2.8 to ...2.3 deaths per 100 000 women from 2000 to 2015. OBJECTIVE: To update the US Preventive Services Task Force (USPSTF) 2012 recommendation on screening for cervical cancer. EVIDENCE REVIEW: The USPSTF reviewed the evidence on screening for cervical cancer, with a focus on clinical trials and cohort studies that evaluated screening with high-risk human papillomavirus (hrHPV) testing alone or hrHPV and cytology together (cotesting) compared with cervical cytology alone. The USPSTF also commissioned a decision analysis model to evaluate the age at which to begin and end screening, the optimal interval for screening, the effectiveness of different screening strategies, and related benefits and harms of different screening strategies. FINDINGS: Screening with cervical cytology alone, primary hrHPV testing alone, or cotesting can detect high-grade precancerous cervical lesions and cervical cancer. Screening women aged 21 to 65 years substantially reduces cervical cancer incidence and mortality. The harms of screening for cervical cancer in women aged 30 to 65 years are moderate. The USPSTF concludes with high certainty that the benefits of screening every 3 years with cytology alone in women aged 21 to 29 years substantially outweigh the harms. The USPSTF concludes with high certainty that the benefits of screening every 3 years with cytology alone, every 5 years with hrHPV testing alone, or every 5 years with both tests (cotesting) in women aged 30 to 65 years outweigh the harms. Screening women older than 65 years who have had adequate prior screening and women younger than 21 years does not provide significant benefit. Screening women who have had a hysterectomy with removal of the cervix for indications other than a high-grade precancerous lesion or cervical cancer provides no benefit. The USPSTF concludes with moderate to high certainty that screening women older than 65 years who have had adequate prior screening and are not otherwise at high risk for cervical cancer, screening women younger than 21 years, and screening women who have had a hysterectomy with removal of the cervix for indications other than a high-grade precancerous lesion or cervical cancer does not result in a positive net benefit. CONCLUSIONS AND RECOMMENDATION: The USPSTF recommends screening for cervical cancer every 3 years with cervical cytology alone in women aged 21 to 29 years. (A recommendation) The USPSTF recommends screening every 3 years with cervical cytology alone, every 5 years with hrHPV testing alone, or every 5 years with hrHPV testing in combination with cytology (cotesting) in women aged 30 to 65 years. (A recommendation) The USPSTF recommends against screening for cervical cancer in women younger than 21 years. (D recommendation) The USPSTF recommends against screening for cervical cancer in women older than 65 years who have had adequate prior screening and are not otherwise at high risk for cervical cancer. (D recommendation) The USPSTF recommends against screening for cervical cancer in women who have had a hysterectomy with removal of the cervix and do not have a history of a high-grade precancerous lesion or cervical cancer. (D recommendation)
Abstract Objectives High attendance rates in cervical screening are essential for effective cancer prevention. Offering HPV self-sampling to non-responders increases participation rates. The ...objectives of this study were to determine why non-responders do not attend regular screening, and why they do or do not participate when offered a self-sampling device. Methods A questionnaire study was conducted in the Netherlands from October 2011 to December 2012. A total of 35,477 non-responders were invited to participate in an HPV self-sampling study; 5347 women did opt out. Finally, 30,130 women received a questionnaire and self-sampling device. Results The analysis was based on 9484 returned questionnaires (31.5%) with a self-sample specimen, and 682 (2.3%) without. Among women who returned both, the main reason for non-attendance to cervical screening was that they forgot to schedule an appointment (3068; 32.3%). The most important reason to use the self-sampling device was the opportunity to take a sample in their own time-setting (4763; 50.2%). A total of 30.9% of the women who did not use the self-sampling device preferred after all to have a cervical smear taken instead. Conclusions Organisational barriers are the main reason for non-attendance in regular cervical screening. Important reasons for non-responders to the regular screening to use a self-sampling device are convenience and self-control.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
ABSRACT
BACKGROUND
Little is known about whether and how screening for cancers of natal reproductive structures, including cervical cancer, in female-to-male (FTM) transgender individuals differs ...from cancer screening among non-transgender females.
OBJECTIVE
To investigate anecdotal reports from clinicians of high rates of inadequate Papanicolaou (Pap) tests among transgender men.
DESIGN
Results of Pap tests performed on 233 FTM and 3,625 female patients at an urban community health center between 2006 and 2012 were extracted from an electronic medical record.
KEY RESULTS
Compared to female patients, FTM patients were more likely to have an inadequate Pap, with prevalence of inadequate samples 8.3 times higher among tests of FTM patients (10.8 % vs. 1.3 % of tests). FTM patients had over ten times higher odds of having an inadequate Pap after adjusting for age, race, and body mass index (AOR = 10.77, 95 % CI = 6.83, 16.83). When years on testosterone therapy was added to the model, the relationship between transgender identity and Pap inadequacy was attenuated, but remained strongly associated (AOR = 6.01, 95 % CI = 3.00, 11.50), and time on testosterone was also associated (AOR = 1.19, 95 % CI 1.04, 1.36). FTM patients were more likely than females to have had multiple inadequate tests, and had longer latency to follow-up testing.
CONCLUSIONS
The high unsatisfactory sample prevalence among FTM patients is likely due to a combination of physical changes induced by testosterone therapy and provider/patient discomfort with the exam. Clinicians should receive training in increasing comfort for FTM patients during the exam. FTM patients should be alerted that high rates of inadequate screening may require follow-up testing. Alternatives to repeated Pap testing, such as cytologic reprocessing of inadequate samples or primary human papillomavirus (HPV) DNA screening, should be studied for efficacy and acceptability among FTM patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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