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Abstract Background In January 2017, the Dutch cervical cancer screening programme transitioned from cytomorphological to primary high-risk HPV (hrHPV) DNA screening, including the introduction of self-sampling, for women aged between 30 and 60 years. The Netherlands was the first country to switch to hrHPV screening at the national level. We investigated the health impact of this transition by comparing performance indicators from the new hrHPV-based programme with the previous cytology-based programme. Methods We obtained data from the Dutch nationwide network and registry of histo- and cytopathology (PALGA) for 454,573 women eligible for screening in 2017 who participated in the hrHPV-based programme between 1 January 2017 and 30 June 2018 (maximum follow-up of almost 21 months) and for 483,146 women eligible for screening in 2015 who participated in the cytology-based programme between 1 January 2015 and 31 March 2016 (maximum follow-up of 40 months). We compared indicators of participation (participation rate), referral (screen positivity; referral rate) and detection (cervical intraepithelial neoplasia (CIN) detection; number of referrals per detected CIN lesion). Results Participation in the hrHPV-based programme was significantly lower than that in the cytology-based programme (61% vs 64%). Screen positivity and direct referral rates were significantly higher in the hrHPV-based programme (positivity rate: 5% vs 9%; referral rate: 1% vs 3%). CIN2+ detection increased from 11 to 14 per 1000 women screened. Overall, approximately 2.2 times more clinical irrelevant findings (i.e. ≤CIN1) were found in the hrHPV-based programme, compared with approximately 1·3 times more clinically relevant findings (i.e. CIN2+); this difference was mostly due to a national policy change recommending colposcopy, rather than observation, of hrHPV-positive, ASC-US/LSIL results in the hrHPV-based programme. Conclusions This is the first time that comprehensive results of nationwide implementation of hrHPV-based screening have been reported using high-quality data with a long follow-up. We have shown that both benefits and potential harms are higher in one screening round of a well-implemented hrHPV-based screening programme than in an established cytology-based programme. Lower participation in the new hrHPV programme may be due to factors such as invitation policy changes and the phased roll-out of the new programme. Our findings add further to evidence from trials and modelling studies on the effectiveness of hrHPV-based screening.

Background: High-risk human papillomavirus (hrHPV) testing on self-collected samples has potential as a primary screening tool in cervical screening, but real-world evidence on its accuracy in hrHPV-based screening programmes is lacking. Methods: In the Netherlands, women aged 30–60 years invited for cervical screening can choose between sampling at the clinician's office (Cervex Brush) or self-sampling at home (Evalyn Brush). HrHPV testing is performed using Roche Cobas 4800. We collected screening test results between January 2017 and March 2018 and histological follow-up until August 2019. The main outcome measures were mean cycle threshold (Ct) value, cervical intraepithelial neoplasia (CIN) grade 3 or cancer (CIN3+) and CIN grade 2 or worse (CIN2+). Findings: 30,808 women had a self-collected and 456,207 had a clinician-collected sample. In hrHPV-positive women with adequate cytology, Ct values were higher for self-collection than clinician-collection with a mean Ct difference of 1·25 (95% CI 0·98–1·52) in women without CIN2+, 2·73 (1·75–3·72) in CIN2 and 3·59 (3·03–4·15) in CIN3+. The relative sensitivity for detecting CIN3+ was 0·94 (0·90–0·97) for self-collection versus clinician-collection and the relative specificity was 1·02 (1·02–1·02). Interpretation: The clinical accuracy of hrHPV testing on a self-collected sample for detection of CIN3+ is high and supports its use as a primary screening test for all invited women. Because of the slightly lower sensitivity of hrHPV testing on a self-collected compared to a clinician-collected sample, an evaluation of the workflow procedure to optimise clinical performance seems warranted. Funding: National Institute for Public Health and the Environment (the Netherlands) and the European Commission.

Synthetic aperture radar (SAR) acquisitions are mainly deemed suitable for mapping dynamic land-cover and land-use scenarios due to their timeliness and reliability. This particularly applies to Sentinel-1 imagery. Nevertheless, the accurate mapping of regions characterized by a mixture of crops and grasses can still represent a challenge. Radar time-series have to date mainly been exploited through backscatter intensities, whereas only fewer contributions have focused on analyzing the potential of interferometric information, intuitively enhanced by the short revisit. In this paper, we evaluate, as primary objective, the added value of short-temporal baseline coherences over a complex agricultural area in the São Paulo state, cultivated with heterogeneously (asynchronously) managed annual crops, grasses for pasture and sugarcane plantations. We also investigated the sensitivity of the radar information to the classification methods as well as to the data preparation and sampling practices. Two supervised machine learning methods—namely support vector machine (SVM) and random forest (RF)—were applied to the Sentinel-1 time-series at the pixel and field levels. The results highlight that an improvement of 10 percentage points (p.p.) in the classification accuracy can be achieved by using the coherence in addition to the backscatter intensity and by combining co-polarized (VV) and cross-polarized (VH) information. It is shown that the largest contribution in class discrimination is brought during winter, when dry vegetation and bare soils can be expected. One of the added values of coherence was indeed identified in the enhanced sensitivity to harvest events in a small but significant number of cases.

Agriculture is of huge economic significance in The Netherlands where the provision of real-time, reliable information on crop development is essential to support the transition towards precision agriculture. Optical imagery can provide invaluable insights into crop growth and development but is severely hampered by cloud cover. This case study in the Flevopolder illustrates the potential value of Sentinel-1 for monitoring five key crops in The Netherlands, namely sugar beet, potato, maize, wheat and English rye grass. Time series of radar backscatter from the European Space Agency’s Sentinel-1 Mission are analyzed and compared to ground measurements including phenological stage and height. Temporal variations in backscatter data reflect changes in water content and structure associated with phenological development. Emergence and closure dates are estimated from the backscatter time series and validated against a photo archive. Coherence data are compared to Normalized Difference Vegetation Index (NDVI) and ground data, illustrating that the sudden increase in coherence is a useful indicator of harvest. The results presented here demonstrate that Sentinel-1 data have significant potential value to monitor growth and development of key Dutch crops. Furthermore, the guaranteed availability of Sentinel-1 imagery in clouded conditions ensures the reliability of data to meet the monitoring needs of farmers, food producers and regulatory bodies.

Space-based remote sensing imagery can provide a valuable and cost-effective set of observations for mapping crop-productivity differences. The effectiveness of such signals is dependent on several conditions that are related to crop and sensor characteristics. In this paper, we present the dynamic behavior of signals from five Synthetic Aperture Radar (SAR) sensors and optical sensors with growing sugarcane, focusing on saturation effects and the influence of precipitation events. In addition, we analyzed the level of agreement within and between these spaceborne datasets over space and time. As a result, we produced a list of conditions during which the acquisition of satellite imagery is most effective for sugarcane productivity monitoring. For this, we analyzed remote sensing data from two C-band SAR (Sentinel-1 and Radarsat-2), one L-band SAR (ALOS-2), and two optical sensors (Landsat-8 and WorldView-2), in conjunction with detailed ground-reference data acquired over several sugarcane fields in the state of São Paulo, Brazil. We conclude that satellite imagery from L-band SAR and optical sensors is preferred for monitoring sugarcane biomass growth in time and space. Additionally, C-band SAR imagery offers the potential for mapping spatial variations during specific time windows and may be further exploited for its precipitation sensitivity.

After publication of the research paper [...]

Current space-based SAR offers unique opportunities to classify vegetation types and to monitor vegetation growth due to its frequent acquisitions and its sensitivity to vegetation geometry. However, SAR signals also experience frequent temporal fluctuations caused by precipitation events, complicating the mapping and monitoring of vegetation. In this paper, we show that the influence of a priori known precipitation events on the signals can be used advantageously for the classification of vegetation conditions. For this, we exploit the change in Sentinel-1 backscatter response between consecutive acquisitions under varying wetness conditions, which we show is dependent on the state of vegetation. The performance further improves when a priori information on the soil type is taken into account.

Background: In the Netherlands, lower high-risk human papillomavirus (hrHPV) positivity but higher cervical intraepithelial neoplasia (CIN) 2+ detection were found in self-collected compared with clinician-collected samples. To investigate the possible reason for these differences, we compared sociodemographic and screening characteristics of women and related these to screening outcomes. Methods: We extracted data from PALGA on all primary hrHPV screens and associated follow-up tests for 857,866 screened women, invited in 2017 and 2018. We linked these data with sociodemographic data from Statistics Netherlands. Logistic regression was performed for hrHPV positivity and CIN 2+/3+ detection. Results: Out of the 857,866 women, 6.8% chose to use a self-sampling device. A higher proportion of self-sampling users was ages 30 to 35 years, was not previously screened, was living in a one-person household, or was the breadwinner in the household. After adjustment for these factors self-sampling had lower hrHPV positivity (aOR, 0.65; 95% CI, 0.63-0.68)) as compared with clinician-collected sampling, as well as lower odds of CIN 2+ (aOR, 0.76; 95% CI, 0.70-0.82) and CIN 3+ (aOR, 0.86; 95% CI, 0.78-0.95) detection. Conclusions: It is likely that the observed differences between the two sampling methods are not only related to sociodemographic differences, but related to differences in screening test accuracy and/or background risk. Impact: Self-sampling can be used for targeting underscreened women, as a more convenient screening tool. Further investigation is required to evaluate how to implement self-sampling, when it is used as a primary instrument in routine screening. [ABSTRACT FROM AUTHOR]

ObjectivesOur aim was to assess incidence and persistence of oral HPV infection in HIV-negative and HIV-infected men who have sex with men (MSM).MethodsMSM aged ≥18 years were included in Amsterdam (the Netherlands) in 2010-2011, and followed up 6 months later. Participants completed risk factor questionnaires. HPV DNA was analyzed in oral-rinse and gargle specimens using the SPF10-PCR DEIA/LiPA25 system (version 1). A subset of oral samples was subjected to SPF10 sequencing to identify additional HPV types. Multivariable logistic regression analyses using generalized estimating equations (GEE) were performed to assess determinants for oral high-risk HPV incidence and persistence.Results689/795 participant MSM provided both baseline and 6-month data. Baseline prevalence of high-risk HPV was 9.4% in HIV-negative and 23.9% in HIV-infected MSM (PConclusionIncidence of oral high-risk HPV infection in MSM is substantial, and is associated with HIV infection. Over a third of HPV infections persisted over a 6-month period.

High-risk human papillomavirus (HPV) infections are the cause of nearly all cases of cervical cancer. Although the detection of HPV DNA has proved useful in cervical diagnosis, it does not necessarily predict disease presence or severity, and cannot conclusively identify the causative type when multiple HPVs are present. Such limitations may be addressed using complementary approaches such as cytology, laser capture microscopy, and/or the use of infection biomarkers. One such infection biomarker is the HPV E4 protein, which is expressed at high level in cells that are supporting (or have supported) viral genome amplification. Its distribution in lesions has suggested a role in disease staging. Here we have examined whether type-specific E4 antibodies may also allow the identification and/or confirmation of causal HPV-type. To do this, type-specific polyclonal and monoclonal antibodies against three E4 proteins (HPV-16, -18, and -58) were generated and validated by ELISA and western blotting, and by immunohistochemistry (IHC) staining of epithelial rafts containing these individual HPV types. Type-specific detection of HPV and its associated disease was subsequently examined using formalin-fixed paraffin-embedded cervical intra-epithelial neoplasias (CIN, (n = 247)) and normal controls (n = 28). All koilocytotic CIN1 lesions showed type-specific E4 expression of their respective HPV types. Differences were noted amongst E4 expression patterns in CIN3. HPV-18 E4 was not detected in any of the 6 HPV-18 DNA-positive CIN3 lesions examined, whereas in HPV-16 and -58 CIN3, 28/37 (76%) and 5/9 (55.6%) expressed E4 respectively, usually in regions of epithelial differentiation. Our results demonstrate that type-specific E4 antibodies can be used to help establish causality, as may be required when multiple HPV types are detected. The unique characteristics of the E4 biomarker suggest a role in diagnosis and patient management particularly when used in combination.

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International surveys find HPV‐negativity in up to 30% of cervical adenocarcinomas. We investigated the pathological diagnosis by expert consensus with immunohistochemistry and the presence of somatic mutations in recognised tumour genes in HPV‐positive and negative cervical adenocarcinomas (CADC). A sample was selected of 45 paraffin‐embedded cervical blocks diagnosed locally as usual cervical adenocarcinoma from a global study. These represented different diagnoses made at previous diagnostic review and HPV status. All were suitable for analysis for somatic tumour associated gene mutations. Three pathologists examined H/E slides and immunohistochemistry for p16, progesterone receptor and p53 and classified the cases. L1 genes from high‐risk HPVs and low‐risk HPVs were analysed by SPF10 PCR‐DEIA‐LiPA25 version 1 in whole tissue sections and microdissected tumour and retested by PCR for E6/E7 genes of hrHPVs if negative. Cases were analysed for microsatellite instability and next‐generation sequencing mutation analysis. From the 45 cases, 20 cases of usual CADC were confirmed of which 17 (85%) were HPV‐positive in tumour cells. The other 25 cases were reclassified as endometrial, serous, clear‐cell and gastric‐type adenocarcinomas and all were HPV‐negative in tumour cells. Careful retesting for HPV DNA and IHC leads to more accurate identification of HPV‐positive usual cervical adenocarcinomas. Endometrioid endometrial adenocarcinomas, other uterine adenocarcinoma with multiple somatic mutations were important in misclassification of HPV‐negative cases locally managed as cervical adenocarcinoma, as was gastric‐type adenocarcinoma with germline STK11 mutation in East Asia. Few consensuses confirmed HPV‐negative usual cervical adenocarcinomas showed somatic tumorigenic mutations also seen in some HPV‐positive usual CADC. What's new? As many as 30 percent of cervical adenocarcinomas initially test negative for human papillomavirus (HPV), which is necessary but not sufficient for the development of cervical cancer. Here, the authors carried out an extensive survey of different categories of adenocarcinoma initially diagnosed and managed as cervical adenocarcinoma. Analyses show that misdiagnosis of endometrioid endometrial cancer and serous or clear cell cancers as cervical adenocarcinoma are not infrequent and that HPV‐negative cervical adenocarcinoma is a real, though infrequent diagnosis. The findings highlight issues of misdiagnosis and the role of somatic or germ‐line mutations in tumor genes in cervical adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background Oropharyngeal cancer incidence is rapidly rising due to human papillomavirus (HPV) type 16 infection. The dearth of data on effectiveness of national female-only vaccination programs in preventing oral HPV infection and potential herd immunity in unvaccinated males has resulted in considerable controversy regarding the need to vaccinate males, especially in countries with high female vaccination coverage. Methods Subjects aged 0–65 years undergoing tonsillectomy for nonmalignant indications were recruited in 6 hospitals in the United Kingdom. Oral samples were collected as follows: oral rinse, tongue base, and pharyngeal wall brushes, then tonsil tissue (tonsillectomy). Vaccination data were obtained from regional health authorities. All samples were centrally tested for HPV DNA by polymerase chain reaction. Results Of 940 subjects, 243 females and 69 males were aged 12–24 years (median age, 18.6 years), with 189 (78%) females and no males vaccinated against HPV. Overall, oropharyngeal HPV-16 prevalence was significantly lower in vaccinated versus unvaccinated females (0.5% vs 5.6%, P =.04). In contrast, prevalence of any oropharyngeal HPV type was similar in vaccinated and unvaccinated females (19% vs 20%, P =.76). Oropharyngeal HPV-16 prevalence in unvaccinated males was similar to vaccinated females (0% vs 0.5%, P >.99), and lower than unvaccinated females (0% vs 5.6%, P =.08). Conclusions Our findings indicate that the UK female-only vaccination program is associated with significant reductions in oropharyngeal HPV-16 infections. These are also the first data to suggest potential herd immunity from female-only vaccination against oropharyngeal HPV infection in contemporaneously aged males. [ABSTRACT FROM AUTHOR]