Trends in the use of cervical cancer screening tests in a large medical claims database, United States, 2013-2019.

OBJECTIVE: To examine trends in the use of cervical cancer screening tests during 2013-2019 among commercially insured women. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Audit of laboratory sensitivity of human papillomavirus and cytology testing in a cervical screening program.

The globally recommended public health policy for cervical screening is primary human papillomavirus (HPV) screening with cytology triaging of positives. To ensure optimal quality of laboratory services we have conducted regular audits of cervical smears taken before cervical cancer or cancer in situ (CIN3+) within an HPV-based screening program. The central cervical screening laboratory of Stockholm, Sweden, identified cases of CIN3+ who had had a previous cervical screening test up to 3 years before and randomly selected 300 cervical liquid-based cytology (LBC) samples for auditing. HPV testing with Roche Cobas was performed either at screening or with biobanked samples. HPV negative samples and subsequent biopsies were retrieved and tested with modified general primer HPV PCR and, if still HPV-negative, the LBCs and biopsies were whole genome sequenced. The Cobas 4800 detected HPV in 1020/1052 (97.0%) LBC samples taken before CIN3+. Further analyses found HPV in 28 samples, with nine of those containing HPV types not targeted by the Cobas 4800 test. There were 4 specimens (4/1052, 0.4%) where no HPV was detected. By comparison, the proportion of CIN3+ cases that were positive in a previous cytology were 91.6%. We find that the routine HPV screening test had a sensitivity in the real-life screening program of 97.0%. Regular laboratory audits of cervical samples taken before CIN3+ can be readily performed within a real-life screening program and provide assurance that the laboratory of the real-life program has the expected performance.

Impact of education on institutional and faculty rates of atypical squamous cells.

INTRODUCTION: Papanicolaou test quality metrics include the ASC rate, ASC:SIL ratio, and ASC HPV+ rate. What a laboratory should do when metrics show a worrisome trend is not well defined. In 2015, our laboratory noted a worrisome trend in our quality metrics and decided to implement a systemic education program in 2016; we monitored the effectiveness of our program. METHODS: An educational intervention was designed for March/April 2016. Cytotechnologist education consisted of: group meeting on March 10 to discuss metrics, lecture, and written materials on ASC-US criteria, a quiz on challenging ASC-US cases, encouragement to seek consultation, and each cytotechnologist received quarterly individual metrics. The cytopathologist education consisted of: group meeting on April 16 to discuss metrics, encouragement to bring borderline cases to consensus conference, and each faculty received quarterly individual metrics. The ASC rate, ASC:SIL ratio, and ASC HPV+ rate was collected for the institution and each individual faculty in 2016 for January to March (pre-interventions, Q1), April to June (post-interventions, Q2), and July to September (post-interventions, Q3). ASC-H was included in the calculation of ASC %, ASC:SIL, and ASC HPV+ rates. RESULTS: There was a substantial decline in the lab ASC rate and ASC:SIL ratio, and the ASC HPV+ rate increased. Individual faculty changes in ASC:SIL ratio and ASC HPV+ rate also improved. CONCLUSIONS: In our institution, an educational program has been very effective in improving Papanicolaou test metrics. It is helpful to perform re-education at all levels within the department.

Lesion-targeted cytology to improve cytological sampling for atypical polypoid adenomyomas of the uterus: A case series and review of the literature.

OBJECTIVE: Atypical polypoid adenomyomas (APAs) are uncommon tumours consisting of atypical endometrioid glands and fibromyomatous stroma. Identifying the biphasic nature of atypical glandular components and spindle mesenchymal components without atypia is crucial for the cytological diagnosis of APA. We investigated the utility of lesion-targeted cytology (LTC) to directly collect firm spindle components. METHODS: We recruited seven consecutive surgical patients who underwent cytological examinations before surgery and were diagnosed with APA on postoperative histological examinations. Cytological smears were obtained by routine sampling in five cases and by targeted sampling using transvaginal ultrasonography, that is, LTC, in two cases. We retrospectively analysed the cytological findings from our cases and compared them to those of APA cases previously reported in the English literature. RESULTS: Among 5/7 cases that involved routine cytological sampling, normal cytological findings were found in 2 and atypical glandular cells were found in 3, but spindle cells from mesenchymal components were not detected. In contrast, among 2/7 cases in which sampling involved LTC, spindle cells without atypia, in addition to atypical glandular cells were found. CONCLUSIONS: Lesion-targeted cytology is useful to assess mesenchymal components of APAs and may improve the cytological diagnosis of APA.

Comparison Study of Self-Sampled and Physician-Sampled Specimens for High-Risk Human Papillomavirus Test and Cytology.

OBJECTIVE: The objective of this study was to calculate the positive rate and overall concordance rate of high-risk human papillomavirus (hrHPV) test and cytology using self-sampled and physician-sampled cervicovaginal tests and to compare both specimens. METHODS: In collaboration with 3 private hospitals in Sapporo city, 300 women visiting these organizations were enrolled in the study by previously signing an informed consent. From these women, both types of samples (self-obtained and physician-sampled) were obtained at the same time. HrHPV test and cytology were performed on both specimens, and the positive rate and overall concordance rate were calculated to compare both specimens. RESULTS: HrHPV-positive women were 13.7% in physician-sampled specimens and 14.7% in self-sampled specimens, with an overall concordance rate of 96.3% (95% confidence interval [CI]: 94-98%). On the other hand, the positive rate of the cases higher than or equal to atypical squamous cells of undetermined significance (ASCUS) on cytology was different between both groups, that is, 12.3% in physician-obtained and 5.3% in self-sampled specimens; the overall concordance rate was 90.7% (95% CI: 87-94%), indicating an apparent decrease in the positive rate of cytology in self-obtained specimens. CONCLUSION: HrHPV test and cytology were performed on parallel samples obtained by the patients with a self-sampling tool and by the physician. The positive rate of cytology was considerably different between these specimens, while almost equivalent results were obtained for hrHPV test in both specimens. It was concluded that hrHPV test may be safely and accurately performed on self-obtained cervicovaginal samples by the help of a self-sampling device in the Japanese population as a first screening tool, with equivalent results to physician-obtained specimens.

Efficacy of strategies to increase participation in cervical cancer screening: GPs offering self-sampling kits for HPV testing versus recommendations to have a pap smear taken - A randomised controlled trial.

Background: Cervical cancer is preventable by early detection and treatment of pre-cancerous lesions. The current screening policy in Belgium (3-yearly cytology on Pap smears) covers 60% of the target population. Offering self-samples by GPs can overcome barriers for women who are currently not screened. Methods: Women aged 25­64 who did not have a Pap smear since three years and consulted a GP practice in a Flemish municipality between November 2014 and April 2015 were allocated in a 1:1 ratio to either the intervention arm where women were given a vaginal self-sampling kit or control arm where women were encouraged to make an appointment for having a Pap smear taken by a clinician. Results: Eighty-eight consenting women were randomised. 35 (78%) out of 45 women in the self-sampling arm participated in screening compared to 22 (51%) out of 43 women in the control arm (p = 0.009). This difference remained significant after adjusting for covariates (age category, education level, time interval since last Pap smear, past Pap smear-taker). Conclusion: GPs offering self-sampling kits resulted in a high participation. Larger trials should confirm this effect and evaluate feasibility of this approach.4. The authors would also like to include the following sentence in the acknowledgement "The laboratory AML (Antwerp, Belgium) is acknowledged for the free HPV testing on the self-samples."

The Quality of Pap Smears from the Brazilian Cervical Cancer Screening Program According to the Human Development Index.

Brazil is a country with strong socioeconomic disparities, which may explain the different rates of cervical cancer incidence and mortality and influence the quality of cervical cancer screening tests. The aim of this study was to perform a trend analysis of some quality indicators of Pap smears according to the Municipal Human Development Index (MHDI). Information about cytopathological exams (approximately 65,000,000) performed from 2006 to 2014 in women ages 25 to 64 years was obtained from the Cervical Cancer Information System (SISCOLO). The average annual percentage change (AAPC) for each indicator was calculated using the Joinpoint Regression Program, according to MHDI levels. Very low frequencies of unsatisfactory cases (<5%) were observed at different MHDI levels. Although the positivity index in the low- and medium-MHDI groups has increased, the values remained below international recommendations (3%-10%). The HSIL (high-grade squamous intraepithelial lesion) percentage remained stationary at all levels of the MHDI. In the low- and medium-MHDI groups, most quality indicators were below the recommendations by Brazilian National Cancer Institute INCA, with no improvement trend; in the high-MHDI group, the majority of the indicators also presented no improvement, although they show slightly better quality indicators. The MHDI should be considered in the definition of the policies of the screening program for cervical cancer in Brazil, and the current program may require adjustments to achieve improved efficiency.

Quality control of cervical cytology using a 3-type HPV mRNA test increases screening program sensitivity of cervical intraepithelial neoplasia grade 2+ in young Norwegian women-A cohort study.

Within 2021, Norway intends to complete implementation of HPV DNA-based primary screening for cervical cancer for women 34-69 years, while continue cytology-based screening for women 25-33 years. Over the recent years, the incidence of cervical cancer has increased by 30% among women younger than 40 years. In this subset of women, nearly 30% were diagnosed with a normal smear, as most recent smear, prior the cancer diagnosis. This observation demands quality control of normal smears. The aim of this study was to assess increase in program sensitivity of CIN2+ after follow-up of women with false negative Pap-smears testing positive for a 3-type (-16, -18, -45) HPV mRNA test in a cohort design over one screening interval. 521 women, aged 23-39 years, and no prior history of CIN1+ or HSIL, with an ASC-US or worse smear (ASC-US+) and 1444 women with normal screening cytology comprised the study cohorts. The positivity rate for the 3-type HPV mRNA was 1.9% (28/1444). Rescreening revealed 23 women with ASC-US, two women with LSIL, two women with ASC-H, and one woman with AGUS. If the HPV mRNA-positivity rate and histology findings from samples rescreened were applied to all women with normal cytology, an estimated increase in screening sensitivity of 16.4% (95% CI:15.3-17.5) for CIN2+ and 17.3% (95% CI:16.2-18.4) for CIN3+ were achieved. By rescreening less than 2% of women with normal cytology positive for a 3-type HPV mRNA test, we achieved a significant increase in screening program sensitivity.

Comparison of cytological and immunocytochemical methods for detecting apoptotic epithelial cells in cervicovaginal smears.

BACKGROUND: Several methods have been applied to detect death cells in tissue, cell culture, and fluid samples. We aimed to compare the cytological and immunocytochemical methods for detecting apoptotic cells in cervicovaginal smears. METHODS: Cervicovaginal smears were taken from 102 women for various gynecological complaints. The slides were stained using the Papanicolaou (Pap)-staining method for cytological evaluation. Cleaved caspase 3 (CC3) antibody was used to detect apoptosis by immunocytochemically, and H-Score was used for the evaluation. In Pap-stained smears, apoptosis was detected and evaluated using our new scoring system by the examination of morphological changes of epithelial cells such as apoptotic bodies, blebbing, karyopyknosis, karyorrhexis, and karyolysis. We used Kappa analysis to understand whether there is an agreement between cytological and immunocytochemical methods for detecting apoptotic cells. RESULTS: Cytological and immunocytochemical methods showed similarities at a moderate level (κ = 0.482, P < .001). The cytological and immunocytochemical scores were also similar to each other at a fair level (κ = 0.373, P < .001). Pap smears had a sensitivity of 64.40% (95% CI: 50.12-76.01), specificity of 86.04% (95% CI: 72.65-94.83), positive likelihood ratio of 4.62, negative likelihood ratio of 0.41, positive predictive value of 86.36%, negative predictive value of 63.79%, and overall probability of 73.53% compared to immunocytochemical staining. CONCLUSIONS: Our results demonstrate that Pap smear and cytological scores alone were not good enough to identify apoptosis compared to the immunocytochemical studies. However, because of its high specificity, it may still be an adequate method to detect apoptotic cells.

Clinical Controversies in Cervical Cancer Screening.

Through the implementation of systematic cervical cancer screening in the mid-20th century, the United States and other developed countries have seen death rates from cervical cancer decreased by ≥70%.The purpose of this article is to address several of the most controversial issues associated with cervical cancer screening recommendations in light of historical and evolving data. In this article, we will explore the controversies around the age at which to initiate and exit screening, human papilloma virus testing alone as a primary screening approach, and the impact of human papilloma virus vaccination on cervical cancer rates.

A worm in the cytology laboratory: A root cause analysis case study.

In the spring of 2018, nematode-like organisms were first noted at the time of microscopic diagnosis on gynecologic (GYN) and anal pap specimens in our institution's cytopathology department. Due to their morphology and specimen source, we considered a diagnosis of pinworm. However, after identifying at least 30 more cases over 3 months from patients living in variable locations, we started favoring a contaminant. This report studies the steps that were initiated to figure the source of pap smear-preparation contamination and the molecular investigation to identify the nature of the contaminant.

Feasibility, Acceptability, and Accuracy of Vaginal Self-Sampling for Screening Human Papillomavirus Types in Women from Rural Areas in Senegal.

Vaginal self-sampling and human papillomavirus (HPV) DNA testing can be useful tools for women with limited access to health care living in sub-Saharan Africa. To assess the feasibility and acceptability of vaginal self-sampling and high-risk HPV prevalence in two villages of central Senegal, women were asked to self-sample vaginal swabs for HPV detection in May, 2016. Vaginal swabs were collected from 133 women and were tested for HPV genotyping. The acceptability rate of vaginal self-sampling was 98.5%, and 99.2% of the women (133/134) used the device correctly. The quality of self-sampling was satisfactory in 100% of the samples; 10.5% of the samples were positive for HPV, including 6% with high-risk HPV types and 4% with low-risk HPV types. This preliminary study indicates that vaginal self-sampling is a valuable strategy for high-risk HPV detection and cervical cancer screening in a population of women not attending gynecologic screening in rural areas of Senegal.

A retrospective validation of the FocalPoint GS slide profiler NFR technology by analysis of interval disease outcomes compared with manual cytology.

BACKGROUND: To the authors' knowledge, published studies reporting on the performance of the FocalPoint GS (FPGS) imaging system have yielded conflicting results to date. However, the results of the MAVARIC study indicated that the FPGS "No Further Review" (NFR) aspect of the technology demonstrated potential and warranted further investigation. The current validation study was performed prior to implementing the NFR slide reporting technology within the routine cervical screening program in Wales, United Kingdom. METHODS: A total of 45,317 SurePath liquid-based cytology cervical screening samples were submitted for FPGS scanning by 4 Welsh laboratories between 2006 and 2011. The current study (Computer Assisted Evaluation, Screening and Reporting [CAESAR]), reports on a comparison between slides categorized as NFR (8130 slides) and slides manually screened as negative (93,473 slides). Both interventions had a subsequent negative quality control screen. RESULTS: The histological outcome rates of cervical intraepithelial neoplasia 2 (CIN-2) (high-grade squamous intraepithelial lesion or worse [HSIL+]) at 2 years and subsequently 3 years after an FPGS NFR result versus a manually screened negative result were compared. Significantly fewer cases were detected in the NFR cohort compared with the manually screened cohort (P = .043 at 2 years and P = .027 at 3 years). When these cases were subcategorized as cancers and precancers, the interval cancer prevalence between NFR and manually screened samples at 2 years and 3 years was similar; however, the interval precancer prevalence for FPGS NFR was significantly lower (P = .023 at 2 years and P = .026 at 3 years) at approximately one-half that of manual screening. CONCLUSIONS: The negative predictive potential of the FPGS NFR technology is higher than that of manual screening, and the technology has quality/throughput benefits to support and enhance a laboratory cervical screening service.

Prevalence of epithelial abnormalities and high-risk human papilloma virus in cervicovaginal Pap smears of population subgroups as a guide toward evidence-based best practice.

BACKGROUND: The 2012 American Society for Colposcopy and Cervical Pathology Consensus Guidelines provide information for managing abnormal cervical cancer screening tests and cancer precursors. According to these guidelines for Pap smear diagnosis of Atypical squamous cells of undetermined significance, reflex high risk (HR) human papilloma virus (HPV) genotyping is required among women 21 years of age or older. Whereas, in women of 30 to 65 years of age, HR-HPV can be ordered by the clinicians as part of co-testing with any diagnosis and every 5 years with a negative Cervico-Vaginal Pap test (CVPT). METHODS: A retrospective review of the CoPath database of the Pathology Department at the University of Florida, College of Medicine Jacksonville, FL, was performed to identify North Florida (NF) women who underwent CVPT and HR-HPV testing between 2006 and 2014. The women were stratified by race and age, respectively. RESULTS: The study included 19,933 CVPTs. Significant differences in the outcomes' distributions were found among age and race groups, respectively. Highest prevalence of HPV positivity was found in African American women, and in 14- to 20-year-old women, respectively. Twenty- to 30-year-old women had the highest percentage (59%) of epithelial abnormality. The most common HR-HPV genotypic distribution was other HR-HPV. CONCLUSIONS: This study underscores the importance of using both HR-HPV and CVPT for screening for cervical cancer, and confirms the need for special focus on managing high-risk populations subgroups, such as African American women, and women of ages 14 to 20 years especially in high-risk populations.

Ensuring quality in cervical screening programmes based on molecular human papillomavirus testing.

The increased use of human papillomavirus testing within cervical screening programmes necessarily brings about changes to the laboratory services required to support them. A crucial element of such services is to demonstrate initial and ongoing quality of the test (and associated processes). In this review, we outline some of the quality considerations and challenges with an emphasis on the laboratory including assay and platform validation, internal quality control selection and strengths and weaknesses of external quality assurance schemes. The influence and role of key external entities, including regulatory agencies, guideline groups, programme commissioners and commercial providers, are also discussed.

Evaluation of patient- versus provider-collected vaginal swabs for microbiome analysis during pregnancy.

OBJECTIVE: We aimed to evaluate if patient- and provider-collected vaginal swabs in pregnant women reflect similar bacterial community characteristics. Pregnant patients performed a self-collected vaginal swab, then underwent a provider-collected swab via speculum exam. DNA pyrosequencing of the 16S rRNA gene V1V3 and V3V5 variable regions was performed. Relative abundance of taxa, alpha diversity, and beta diversity of patient- and provider-collected swabs were compared. RESULTS: Ninety-four vaginal swabs from 47 women were analyzed. On non-metric multi-dimensional scaling plots, paired patient- and provider-collected swabs clustered closely. The median Pearson correlation coefficient was 0.993 (interquartile range 0.951-0.999) for V1V3 and 0.987 (interquartile range 0.902-0.999) for V3V5. Among paired V1V3 and V3V5 sequences, 83.0% and 73.9% showed strong Pearson correlation (> 0.9), respectively, between patient- and provider-collected swabs; V1V3 and V3V5 sequences with weaker Pearson correlation (< 0.9) had correlation coefficients 0.57-0.89 and 0.49-0.89, respectively. No taxa were preferentially detected by sampling method, with relative abundance of taxa highly conserved. No significant difference in Shannon diversity for V1V3 (p = 0.22) and V3V5 (p = 0.11) sequences among paired samples was seen. We demonstrate that bacterial communities defined from patient- and provider-collected vaginal swabs in pregnant women are similar, validating utilization of patient-collected swabs for vaginal bacterial microbiome sampling during pregnancy.

Screening for Cervical Cancer: US Preventive Services Task Force Recommendation Statement.

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).

Good concordance of HPV detection between cervico-vaginal self-samples and general practitioner-collected samples using the Cobas 4800 HPV DNA test.

BACKGROUND: Studies comparing self-samples and clinician-collected samples for high-risk human papillomavirus (HPV) detection using clinically validated PCR-based HPV DNA assays are limited. We measured the concordance of HPV detection between home-based self-sampling and general practitioner (GP) sampling using the Cobas 4800 HPV DNA test and studied women's accept of home-based self-sampling. METHODS: Paired GP-collected samples and cervico-vaginal self-samples were obtained from 213 women aged 30-59 years diagnosed with ASC-US within the cervical cancer screening program. After undergoing cervical cytology at their GP, the women collected a self-sample with the Evalyn Brush at home and completed a questionnaire. Both samples were HPV-tested using the Cobas 4800 test. Histology results were available for those who tested HPV positive in GP-collected samples. RESULTS: We observed good concordance for HPV detection between self-samples and GP-collected samples (κ: 0.70, 95% CI: 0.58-0.81). No underlying CIN2+ cases were missed by self-sampling. Women evaluated that self-sampling was easy (97.2%, 95% CI: 93.9-98.9%) and comfortable (94.8%, 95% CI: 90.9-97.4%). CONCLUSIONS: Home-based self-sampling using the Evalyn Brush and the Cobas 4800 test is an applicable and reliable alternative to GP-sampling.