Assessment of the possible inhibitory effect of carrageenan in human papillomavirus DNA testing by polymerase chain reaction amplification.

We assessed carrageenan's potential to inhibit human papillomavirus (HPV) DNA extraction and amplification in vaginal swab samples collected in a trial, assessing the efficacy of a carrageenan-based gel against HPV infections. Experiment #1 consisted of adding gel (carrageenan-containing or placebo) to swabs and comparing HPV DNA detection by polymerase chain reaction (PCR) to unmanipulated samples collected from the same participants. For Experiments #2 and #3, we tested vaginal samples for inhibition by addition of an internal control and amplification by real-time PCR. Experiment #4 investigated carrageenan's interference with the extraction process by assessing HPV45 detectability in undiluted and diluted HPV45 positive samples (n = 3) with carrageenan versus no gel. In Experiment #1, there was a loss of HPV positivity with the addition of carrageenan (n = 9), but none with placebo gel (n = 5). In Experiments #2 and #3, the absence of the amplified product was observed in samples from the carrageenan arm: 3.3% (1/30) and 0.5% (1/199) of samples. In Experiment #4, HPV45 was not detected in undiluted carrageenan-containing samples, but after 1/50 dilution, the same HPV45 copy number was detected. Carrageenan does not affect the DNA extraction process, and inhibition of HPV DNA amplification by carrageenan occurs infrequently.

Cost-effectiveness of cervical cancer screening with primary HPV testing for unvaccinated women in Sweden.

BACKGROUND: Sweden revised their cervical cancer screening program in 2017 to include cytology-based screening for women aged 23-29 years and primary human papillomavirus (HPV) testing for women aged 30-64 years; however, alternative strategies may be preferred. To inform cervical cancer prevention policies for unvaccinated women, we evaluated the cost-effectiveness of alternative screening strategies, including the current Swedish guidelines. METHODS: We adapted a mathematical simulation model of HPV and cervical cancer to the Swedish context using primary epidemiologic data. We compared the cost-effectiveness of alternative screening strategies that varied by the age to start screening, the age to switch from cytology to HPV testing, HPV strategies not preceded by cytology, screening frequency, and management of HPV-positive/cytology-negative women. RESULTS: We found that the current Swedish guidelines were more costly and less effective than alternative primary HPV-based strategies. All cost-efficient strategies involved primary HPV testing not preceded by cytology for younger women. Given a cost-effectiveness threshold of €85,619 per quality-adjusted life year gained, the optimal strategy involved 5-yearly primary HPV-based screening for women aged 23-50 years and 10-yearly HPV-based screening for women older than age 50 years. CONCLUSIONS: Primary screening based on HPV alone may be considered for unvaccinated women for those countries with similar HPV burdens.

Consistency evaluation of Liferiver, Yaneng, Darui, and the Cobas 4800 test for high-risk human papillomavirus screening.

BACKGROUND: In recent years, several high-risk human papillomavirus (HR-HPV) tests have been developed. The assay capabilities need to be systematically reviewed. Here, we compared the clinical sample performance of three novel HR-HPV assays (Liferiver, Yaneng, and Darui) based on different platforms with the widely adopted cobas4800 test. METHODS: A total of 346 cervical swabs from women who were screened for cervical cancer were analyzed for the presence of 14 HR-HPV genotypes. The distinction between the four assays was investigated by the genotyping and direct sequencing. RESULTS: The positive rates of the four assays ranged from 61.56% to 64.16%. The overall concordance was 88.15%. The Yaneng assays displayed the best sensitivity (100%) and specificity (98.43%). The sensitivity (98.17%) and specificity (98.43%) of the Darui assay were superior to those of the cobas4800 test (97.72% and 93.70%, respectively). The Liferiver assay displayed comparable sensitivity with the cobas4800 test (95.89% and 97.72%, respectively). The specificity of the cobas4800 was lower than that of the Liferiver assay (93.70% vs. 97.64%). CONCLUSIONS: The three novel HR-HPV assays displayed good agreement with the cobas4800 test. The analytical performance of all four fulfilled the requirements of sensitivity and specificity for HR-HPV detection.

A comparative study of extracellular vesicle-associated and cell-free DNA and RNA for HPV detection in oropharyngeal squamous cell carcinoma.

PURPOSE: This study compares the detection sensitivity of two separate liquid biopsy sources, cell-free (cf) DNA/RNA and extracellular vesicle (EV)-associated DNA/RNA (EV-DNA/RNA), to identify circulating Human Papilloma Virus (HPV) DNA/RNA in plasma obtained from patients with oropharyngeal squamous cell carcinoma (OPCSCC). We also report on the longitudinal changes observed in HPV-DNA levels in response to treatment. EXPERIMENTAL DESIGN: A prospective study was conducted that included 22 patients with locally advanced disease and six patients with metastatic OPCSCC. Twenty-three patients had HPV-related OPCSCC defined by p16 immunohistochemistry. Levels of circulating HPV-DNA and HPV-RNA from plasma-derived cf-DNA/RNA and EV-DNA/RNA were quantified using digital droplet PCR. RESULTS: Circulating HPV-DNA was detected with higher sensitivity in cf-DNA compared to EV-DNA at 91% vs. 42% (p = <0.001). Similarly, circulating tumoral HPV-RNA was detected at a higher sensitivity in cf-RNA compared to EV-RNA, at 83% vs. 50% (p = 0.0019). In the locally advanced cohort, 100% (n = 16) of HPV-OPCSCC patients demonstrated a reduction in circulating HPV-DNA levels in cf-DNA following curative treatment, with 81% of patients demonstrating complete clearance to undetectable levels. However, in metastatic HPV-OPCSCC patients (n = 4), HPV-DNA levels did not correlate with treatment response. CONCLUSION: Our study demonstrates that although HPV-DNA/RNA can be detected in EV associated DNA/RNA, cf-DNA/RNA is the more sensitive liquid biopsy medium. As circulating HPV-DNA levels were found to only correlate with treatment response in the locally advanced but not metastatic setting in our small cohort of patients, the use of HPV-DNA as a dynamic biomarker to monitor treatment response requires further evaluation.

Clinical validation of the HPVIR high-risk HPV test on cervical samples according to the international guidelines for human papillomavirus DNA test requirements for cervical cancer screening.

BACKGROUND: The indicating FTA card is a dry medium used for collection of cervical samples. HPVIR is a multiplex real-time PCR test that detects 12 high-risk human papillomavirus types (hrHPV) and provides single genotype information for HPV16, - 31, - 35, - 39, - 51, - 56, and - 59 and pooled type information for HPV18/45 and HPV33/52/58. The aim of this study was to evaluate whether a strategy with cervical samples collected on the FTA card and subsequently analysed with the HPVIR test complies with the criteria of the international guidelines for a clinically validated method for cervical screening. METHODS: We performed a non-inferiority test comparing the clinical sensitivity and specificity of the candidate test (FTA card and HPVIR) with a clinically validated reference test (Cobas® HPV test) based on liquid-based cytology (LBC) samples. Two clinical samples (LBC and FTA) were collected from 896 participants in population-based screening. For evaluation of the specificity we used 799 women without ≥ CIN2, and for clinical sensitivity we used 67 women with histologically confirmed ≥ CIN2. The reproducibility was studied by performing inter- and intra-laboratory tests of 558 additional clinical samples. RESULTS: The clinical sensitivity and specificity for samples collected on the FTA card and analysed using the HPVIR test were non-inferior to samples analysed with the Cobas® HPV test based on LBC samples (non-inferiority test score, p = 1.0 × 10- 2 and p = 1.89 × 10- 9, respectively). Adequate agreement of > 87% was seen in both the intra- and inter-laboratory comparisons. CONCLUSIONS: Samples collected on the indicating FTA card and analysed with HPVIR test fulfil the requirements of the international guidelines and can therefore be used in primary cervical cancer screening.

Implementation of HPV-based Cervical Cancer Screening Combined with Self-sampling Using a Midwifery Network Across Rural Greece: The GRECOSELF Study.

Self-sampling for human papillomavirus (HPV) testing is an alternative to physician sampling particularly for cervical cancer screening nonattenders. The GRECOSELF study is a nationwide observational cross-sectional study aiming to suggest a way to implement HPV-DNA testing in conjunction with self-sampling for cervical cancer screening in Greece, utilizing a midwifery network. Women residing in remote areas of Greece were approached by midwives, of a nationwide network, and were provided with a self-collection kit (dry swab) for cervicovaginal sampling and asked to answer a questionnaire about their cervical cancer screening history. Each sample was tested for high-risk (hr) HPV with the Cobas HPV test. HrHPV-Positive women were referred to undergo colposcopy and, if needed, treatment according to colposcopy/biopsy results. Between May 2016 and November 2018, 13,111 women were recruited. Of these, 12,787 women gave valid answers in the study questionnaire and had valid HPV-DNA results; hrHPV prevalence was 8.3%; high-grade cervical/vaginal disease or cancer prevalence was 0.6%. HrHPV positivity rate decreased with age from 20.7% for women aged 25-29 years to 5.1% for women aged 50-60 years. Positive predictive value for hrHPV testing and for HPV16/18 genotyping ranged from 5.0% to 11.6% and from 11.8% to 27.0%, respectively, in different age groups. Compliance to colposcopy referral rate ranged from 68.6% (for women 25-29) to 76.3% (for women 40-49). For women residing in remote areas of Greece, the detection of hrHPV DNA with the Cobas HPV test, on self-collected cervicovaginal samples using dry cotton swabs, which are provided by visiting midwives, is a promising method for cervical cancer secondary prevention.

Can we predict histological outcome of distinctive cohorts of patients with glandular cell abnormalities on ThinPrep Papanicolaou testing based on human papillomavirus status, age, and associated squamous abnormalities?

BACKGROUND: The cytology diagnosis of glandular cell abnormalities (GCAs) is diagnostically challenging, causing inadequate reproducibility. Histological outcome of GCA on cytology varies from benign to malignant diseases. The goal of this study is to evaluate histological outcome and identify distinctive cohorts of patients with GCA based on human papillomavirus (HPV) status, age, and associated squamous abnormality to stratify the patient into high risk for squamous/glandular lesions. METHODS: From 2012 to 2017, out of 162 088 ThinPrep Papanicolaou tests performed, 998 (0.61%) were reported as GCAs. Histologic follow-up was available in 638 cases and 429 had concurrent HPV results. RESULTS: The overall rate of high-risk human papillomavirus (hrHPV)-positivity (hrHPV+) was 33.6% (144/429 cases). Among the hrHPV+ cases, 18.1% had cervical intraepithelial neoplasia 2/3 (CIN2/3), 3.5% squamous cell carcinoma (SCC), 3.5% cervical adenocarcinoma in situ (AIS)/adenocarcinoma (ADC), and 2.8% endometrial carcinoma. Among hrHPV- cases, 1.4% had CIN2/3, 1.1% AIS/ADC, and 17.5% endometrial carcinoma. The high-grade cervical lesions (CIN2/3/AIS/ADC) were significantly higher in women with hrHPV+ and associated squamous abnormalities compared to hrHPV- and no squamous abnormality in all age groups except patients >65 years. Endometrial carcinoma was most commonly present in women >65 years especially with HPV- and no associated squamous abnormalities. CONCLUSIONS: HPV testing is useful for predicting the risk of high-grade cervical neoplasia in women with GCA especially with associated squamous abnormalities on cytology. The endometrial carcinoma is more frequent in hrHPV- older women. The combination of cytology with knowledge of associated squamous abnormality, hrHPV status, and age can significantly aid in stratifying the patient into high risk for glandular/squamous lesions which facilitates appropriate management of these patients.

Performance of careHPV, hybrid capture 2 and visual inspection with acetic acid for detection of high-grade cervical lesion in Tanzania: A cross-sectional study.

OBJECTIVE: To examine the test performance of careHPV, Hybrid Capture2 (HC2) and visual inspection with acetic acid (VIA) for detection of cytologically diagnosed high-grade cervical lesions or cancer (HSIL+). DESIGN: Cross-sectional study. SETTING: Ocean Road Cancer Institute (ORCI) and Kilimanjaro Christian Medical Center (KCMC), Tanzania. POPULATION: Women attending routine cervical cancer screening. METHOD: We enrolled 4080 women (25-60 years) in the study. The women were interviewed on lifestyle habits, and tested for HIV. A cervical specimen for careHPV testing (performed at ORCI and KCMC), and a liquid-based cytology sample for HPV DNA detection using HC2 (performed at Tuebingen University Hospital, Germany) and for cytology assessment (performed at Vejle Hospital, Denmark) were obtained at a gynecological examination. Subsequently, VIA was performed. With cytology as gold standard, the sensitivity and specificity of careHPV, HC2, and VIA for detection of HSIL+ were calculated. RESULTS: Altogether, 23.6% had a positive careHPV test, 19.1% had positive HC2 test, and 6.3% had a positive VIA test. The sensitivity/specificity was 88.9%/78.9% for careHPV and 91.1%/83.7%, for HC2. VIA showed a low sensitivity of 31.1% but a high specificity (94.6%) for detection of HSIL+. The sensitivity of careHPV, HC2 and VIA was higher among younger women, and among HIV positive women. VIA triage of careHPV positive women improved specificity, but sensitivity dropped to 27%. CONCLUSION: Our results confirm the low sensitivity of VIA for detection of HSIL+ and further document that careHPV test is promising as a primary screening method for cervical-cancer prevention in low-resource regions. A suitable triage test has to be identified.

HPV status in women with high-grade dysplasia on cervical biopsy and preceding negative HPV tests.

INTRODUCTION: A considerable number of patients with high-grade cervical lesions have undergone preceding human papillomavirus (HPV) tests with negative results. In the present study, we attempted to elucidate the factors potentially contributing to the findings by testing biopsied samples from these patients. MATERIALS AND METHODS: Of the 1654 women with HPV testing and follow-up cervicovaginal biopsies from March 1, 2013 to June 30, 2014, 21 of 252 women (8.3%) with biopsy-confirmed high-grade squamous intraepithelial lesion (HSIL) or worse had had negative results from preceding high-risk (hr)HPV tests. The corresponding paraffin blocks were tested for HPV using the Cobas 4800 system, a DNA microarray against 40 HPV genotypes, and DNA sequencing. RESULTS: HPV was detected in 20 (95%) of the 21 biopsies with HSIL or worse, including HPV16/18 in 4, non-16/18 hrHPV in 10, and non-hrHPV in 6. HPV59 and HPV45 were 2.2 times more frequently detected than HPV16/18 in these samples. One sample was negative for all 3 tests (5%). CONCLUSIONS: Our study has demonstrated that 8.3% of women with biopsy-confirmed HSIL or worse had preceding test results that were negative for hrHPV. The vast majority of the biopsied samples had detectable HPV, primarily hrHPV genotypes (67%) with HPV59 and HPV45 predominance. This genotypic prevalence pattern was markedly different from those reported in the general population. Non-hrHPV genotypes contributed to 29% of the cases, and HPV-negative cases were rare. In addition to the limited Cobas testing panel and rare possible HPV-negative HSIL or worse, other possible contributing factors to the discrepancy include cytologic sampling, interference material, technical errors, and reduced L1 gene expression in high-grade lesions.

The reporting rates of atypical glandular cells and their HPV testing and histologic follow-up results: a comparison between ThinPrep and SurePath preparations from a single academic institution.

INTRODUCTION: The interpretation of atypical glandular cells (AGCs) remains a major challenge in gynecologic cytopathology using liquid-based cytology (LBC) (ThinPrep and SurePath). The comparison of performance of detecting glandular abnormalities using these 2 methods is lacking. We investigated the reporting rates of AGCs, human papillomavirus (HPV) testing, and histologic follow-up results in ThinPrep (TP) and SurePath (SP) samples. MATERIALS AND METHODS: In our institution, both TP and SP were utilized during the period between January 2014 and June 2017. A retrospective search was conducted to identify patients with AGCs from 58,591 LBCs (27,041 TP and 31,550 SP). Roche (Pleasanton, CA) cobas HPV testing and histologic follow-up results were collected. RESULTS: The reporting rates of AGCs for TP (0.7%) or SP (0.2%) were within the College of American Pathologists benchmark ranges, but the reporting for TP was significantly greater than that for SP (P < 0.0001). The HPV-positive rates were 26.0% and 19.4% in TP-AGCs and SP-AGCs, respectively, with no statistical significance. A total of 137 (74.9%) TP-AGCs and 54 (74%) SP-AGCs had histologic follow-up. High-grade squamous intraepithelial lesions (HSIL)/squamous cell carcinoma were identified in 8.8% (12 of 137) of TP-AGCs and 13% (7 of 54) of SP-AGCs. Adenocarcinomas including endocervical and endometrial adenocarcinomas were identified in 9.5% (13 of 137) of TP-AGCs and 13% (7 of 54) of SP-AGCs. Together, 18.2% (25 of 137) of TP-AGCs and 25.9% (14 of 54) of SP-AGCs showed either HSIL or carcinoma in histologic follow-up, but with no statistical significance. CONCLUSIONS: TP preparation detected considerably more AGCs than SP preparation. There was no statistical significant difference in HPV-positive rates or histologic follow-up outcomes between TP-detected AGCs and SP-detected AGCs.

Accuracy of Messenger RNA Human Papillomavirus Tests for Diagnostic Triage of Minor Cytological Cervical Lesions: A Systematic Review and Meta-Analysis.

OBJECTIVES: The main objective of this systematic review and meta-analysis is to specify the accuracy of messenger RNA human papillomavirus (HPV) tests among women with previous minor cervical lesion cytology to detect high-grade squamous intraepithelial lesions (CIN2+ and CIN3+) compared with a histopathological reference standard. The secondary objective is to compare messenger RNA HPV test accuracies and the DNA high-risk HPV test among these women. METHODS: Eligible studies were identified by searching the electronic databases with medical subject headings. MAIN RESULTS: Among the 2052 studies identified, 20 primary studies were included. Two tests were mainly identified: Aptima and PreTect HPV-Proofer. Aptima, with 10 studies, had better performance, considering atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion together, with a pooled sensitivity of 90.5% (95% confidence interval [CI], 88.1-92.6) and specificity of 55.1% (95% CI, 53.5-56.8) for CIN2+. For the ASC-US sample, Aptima had a pooled sensitivity of 90.1% (95% CI, 87.1-92.7) and specificity of 59.3% (95% CI, 57.5-61.1). CONCLUSIONS: Messenger RNA HPV tests, mainly Aptima assay, can be recommended to triage women with ASC-US and low-grade squamous intraepithelial lesion because it has higher specificity with a small loss of sensitivity than Hybrid Capture 2 assay; this finding is promising as a means to reduce the overmanagement of minor cytological abnormalities.

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.

Comparison of CerviHPV and Hybrid Capture 2 HPV tests for detection of high-risk HPV infection in cervical swab specimens.

BACKGROUND: Persistent high-risk human papillomavirus (HR-HPV) infection is the etiological cause of virtually all cervical cancer cases. HR-HPV screening achieved with earlier generations of HR-HPV tests has been instrumental in the prevention and early detection of cervical cancer worldwide. The first FDA-approved HR-HPV test, digene Hybrid Capture 2 HPV DNA Test (HC2), has been prominent in these efforts. Newer tests have since been developed to improve upon the capability of HC2 test. METHODS: To evaluate the performance of a new multiplex real-time quantitative PCR assay for HR-HPV detection, CerviHPV HR-HPV Test (CerviHPV), 232 cervical swab specimens were collected and analyzed by HC2 and CerviHPV tests for comparison. RESULTS: HC2 test detected 69 (29.7%) positive cases, whereas CerviHPV test reported 43 (18.5%) positive cases. The concordance rate between the two tests was 84.5% with a kappa value of 0.579. Additional analyses identified only HPV66 or low-risk HPV (LR-HPV) types in six HC2 positive discordant cases, suggesting these HC2 results to be false positive. CONCLUSION: CerviHPV test has two advantages over HC2 test: It contains a cellular control to eliminate false negative results due to failed sample collection and processing, and it can simultaneously detect and genotype the two most carcinogenic HPV types, HPV16 and 18. In this comparison study, CerviHPV test also demonstrated higher analytical specificity for HR-HPV genotypes than HC2 test. Therefore, CerviHPV test has the potential to become a viable option for cervical cancer screening in the clinics.

High grade squamous intraepithelial lesion on high-risk HPV negative patients: Why we still need the Pap test.

BACKGROUND: Cervical cancer is caused by high-risk human papillomavirus (hrHPV). Though screening Pap test (PT) has reduced cancer mortality by detecting precursor lesions, there is now a move toward replacing screening PT with hrHPV testing. The aims of this study were to determine hrHPV negative rate in high grade squamous intraepithelial lesion (HSIL) PT in high-risk patients and correlate with histopathology; and to review the hrHPV negative HSIL PT. METHOD: LIS was searched (January 2015-June 2016) for HSIL PT results. Patient chart was reviewed for age, hrHPV co-testing result including genotyping (Aptima® ), and histopathology follow-up (f/u) which was compared between hrHPV-positive and hrHPV-negative groups. hrHPV-negative HSIL PT slides were re-evaluated for concordance with original interpretation. Student t test was used for data analysis. RESULTS: There were 230 patients with HSIL PT who had hrHPV co-testing and 199/230 had histopathological f/u. Majority (210/230, 91.3%) were hrHPV positive, and 20 (8.7%) were hrHPV negative. HrHPV negative HSIL was significantly more common in older women (mean age 49.3 years) compared with hrHPV-positive HSIL (mean age 40.7 years) (P = .0015). The most frequently detected genotype was HPV16 (40%). F/u was CIN2/3 in 145/181 (80%) hrHPV-positive HSIL (includes nine squamous cell carcinoma) and 6/16 (37.5%) hrHPV-negative HSIL. CONCLUSION: Although the risk of CIN2/3 and carcinoma was higher in hrHPV-positive patients, possibility of hrHPV-negative dysplastic lesions should be considered in older women as 6 of 16 (37.5%) of these women had CIN2/3 and/or carcinoma which would have been missed without the PT.

HPV test result monitoring of different Bethesda categories in gynaecologic cytology: A valuable quality assurance measure.

BACKGROUND: High-risk human papillomavirus (HPV) test ordering has evolved since the 2006 ASCCP guidelines. In light of the availability of the HPV test results for most women ≥30 y, regardless of the Pap test diagnosis; we examined their value in assessing the overall performance of cytopathologists (CPs). METHODS: Data were derived for six CPs for Pap test interpretations over 4 y. HPV positivity rates for atypical squamous cells of undetermined significance (ASC-US) and for patients ≥30 y for negative for intraepithelial lesion or malignancy (NILM) and squamous intraepithelial lesion (SIL) (inclusive of low grade SIL (LSIL), high grade SIL (HSIL), and carcinoma) categories were retrieved for individual CPs. ASC/SIL ratios were analysed overall and separately for patient groups <30 y and ≥30 y. Pearson correlation coefficient was calculated to assess correlation between HPV positivity rates for ASC-US, NILM and SIL, and ASC/SIL ratios. RESULTS: The overall ASC-US HPV positivity rate was 41%-49% for patients <30 y, 32% for patients ≥30 y. Stratifying by patient age group, ASC-US HPV positivity rate, and ASC/SIL ratio showed a negative correlation. Excluding an outlier, the NILM HPV positivity rate and ASC/SIL ratio showed a strong negative correlation. CONCLUSION: Our study shows that ASC-US HPV positivity rate is dependent on the age of the population that is tested. Monitoring of the HPV positivity rates for NILM and SIL categories can serve as an additional objective measure to assess the performance of CPs. Based on the patient population, the laboratory can establish an initial baseline for these rates and use it to adjust interpretive thresholds in ensuring the diagnostic sensitivity of the test and the quality of the interpretation.

Human papillomavirus testing as part of the renewed National Cervical Screening Program.

BACKGROUND: On 1 December 2017, Australia moved to a new National Cervical Screening Program (NCSP), which uses primary human papillomavirus (HPV) nucleic acid testing (NAT) followed by reflex liquid-based cytology for women aged between 25 and 74 years. OBJECTIVE: The aim of this article is to provide an overview of the different HPV NAT assays that satisfy the requirements for use in the renewed NCSP. DISCUSSION: Australia has adopted innovative, evidence-based criteria for the inclusion of HPV NAT assays in the renewed NCSP. These include the requirements for detection of all 12 designated oncogenic HPV types, including separate detection and reporting of HPV 16 and 18; validation against reference assays showing sufficient sensitivity and specificity for the detection of underlying high-grade cervical disease; reproducibility; and the presence of cellularity and inhibition controls. Practitioners can feel assured that HPV NAT undertaken as part of the renewed NCSP will produce high­quality results irrespective of location or pathology provider.

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.

Guidelines for HPV-DNA Testing for Cervical Cancer Screening in Brazil.

Evidence-based clinical guidelines ensure best practice protocols are available in health care. There is a widespread use of human papillomavirus deoxyribonucleic acid (HPV-DNA) tests in Brazil, regardless of the lack of official guidelines. On behalf of the Brazilian Association for the Lower Genital Tract Pathology and Colposcopy (ABPTGIC, in the Portuguese acronym), a team of reviewers searched for published evidence and developed a set of recommendations for the use of HPV-DNA tests in cervical cancer screening in Brazil. The product of this process was debated and consensus was sought by the participants. One concern of the authors was the inclusion of these tests in the assessment of women with cytologic atypia and women treated for cervical intraepithelial neoplasia (CIN). Testing for HPV is recommended in an organized screening scenario to identify women with precursor lesions or asymptomatic cervical cancer older than 30 years of age, and it can be performed every 5 years. It also has value after the cytology showing atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSILs) as a triage test for colposcopy, in the investigation of other cytological alterations when no abnormal findings are observed at colposcopy, seeking to exclude disease, or, further, after treatment of high-grade cervical intraepithelial neoplasia, to rule out residual disease.

O uso de diretrizes clínicas baseadas em evidências visa assegurar as melhores práticas na área de cuidado à saúde. O uso de testes de ácido desoxirribonucleico de papilomavírus humano (DNA-HPV) vem crescendo e se disseminando sem que existam recomendações de uso no cenário brasileiro. Em nome da Associação Brasileira de Patologia do Trato Genital Inferior e Colposcopia (ABPTGIC), grupos de revisores pesquisaram evidências e formularam recomendações para o uso dos testes de DNA-HPV no rastreamento do câncer do colo do útero, no seguimento de mulheres com atipias citológicas, e após tratamento de neoplasia intraepitelial cervical (NIC). O produto desse processo foi debatido e foi buscado consenso entre participantes. Os testes de DNA-HPV são recomendados num cenário de rastreamento organizado para identificação de mulheres portadoras de lesões precursoras ou câncer assintomático com mais de 30 anos e podem ser realizados a cada 5 anos. Também têm valor após a citologia mostrando células escamosas atípicas de significado indeterminado (ASC-US) ou lesão intraepitelial escamosa de baixo grau (LSIL) como teste de triagem para colposcopia, na investigação de outras alterações citológicas quando não são observados achados anormais à colposcopia, buscando excluir doença, ou, ainda, no seguimento após tratamento das neoplasias intraepiteliais de alto grau, para exclusão de doença residual.

Guidelines for HPV-DNA testing for cervical cancer screening in Brazil / Recomendações para o uso de testes de DNA-HPV no rastreamento do câncer do colo útero no Brasil

Abstract Evidence-based clinical guidelines ensure best practice protocols are available in health care. There is a widespread use of human papillomavirus deoxyribonucleic acid (HPVDNA) tests in Brazil, regardless of the lack of official guidelines. On behalf of the Brazilian Association for the Lower Genital Tract Pathology and Colposcopy (ABPTGIC, in the Portuguese acronym), a team of reviewers searched for published evidence and developed a set of recommendations for the use of HPV-DNA tests in cervical cancer screening in Brazil. The product of this process was debated and consensus was sought by the participants. One concern of the authors was the inclusion of these tests in the assessment of women with cytologic atypia and women treated for cervical intraepithelial neoplasia (CIN). Testing for HPV is recommended in an organized screening scenario to identify women with precursor lesions or asymptomatic cervical cancer older than 30 years of age, and it can be performed every 5 years. It also has value after the cytology showing atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSILs) as a triage test for colposcopy, in the investigation of other cytological alterations when no abnormal findings are observed at colposcopy, seeking to exclude disease, or, further, after treatment of high-grade cervical intraepithelial neoplasia, to rule out residual disease.

Resumo O uso de diretrizes clínicas baseadas em evidências visa assegurar as melhores práticas na área de cuidado à saúde. O uso de testes de ácido desoxirribonucleico de papilomavírus humano (DNA-HPV) vem crescendo e se disseminando sem que existam recomendações de uso no cenário brasileiro.Emnomeda Associação Brasileira de Patologia doTrato Genital Inferior e Colposcopia (ABPTGIC), grupos de revisores pesquisaram evidências e formularamrecomendações para o uso dos testes de DNA-HPV no rastreamento do câncer do colo do útero, no seguimento de mulheres com atipias citológicas, e após tratamento de neoplasia intraepitelial cervical (NIC). O produto desse processo foi debatido e foi buscado consenso entre participantes. Os testes de DNA-HPV são recomendados num cenário de rastreamento organizado para identificação de mulheres portadoras de lesões precursoras ou câncer assintomático com mais de 30 anos e podem ser realizados a cada 5 anos. Também têm valor após a citologia mostrando células escamosas atípicas de significado indeterminado (ASC-US) ou lesão intraepitelial escamosa de baixo grau (LSIL) como teste de triagempara colposcopia, na investigação de outras alterações citológicas quando não são observados achados anormais à colposcopia, buscando excluir doença, ou, ainda, no seguimento após tratamento das neoplasias intraepiteliais de alto grau, para exclusão de doença residual.