HPV-Based Self-Sampling in Cervical Cancer Screening: An Updated Review of the Current Evidence in the Literature.

Identifying and reaching women at higher risk for cervical cancer is all-important for achieving the ambitious endpoints set in 2020 by the WHO for global cervical cancer control by 2030. HPV-based (vaginal) self-sampling (SS) represents a cost-effective screening strategy, which has been successfully implemented during the last decade both in affluent and constrained settings. Among other advantages, SS strategies offer convenience, diminished costs, flexibility to obtain a sample in the office or home, avoiding a pelvic exam and uncomfortable appointment with a healthcare professional, as well as social and cultural acceptability. SS implementation has been globally boosted during the COVID-19 pandemic. In pragmatic terms, social distancing, local lockdowns, discontinuation of clinics and reallocation of human and financial resources challenged established clinician-based screening; self-collection strategies apparently surpassed most obstacles, representing a viable and flexible alternative. With time, sufficient reassuring data has accumulated regarding specially designed SS devices, aspects of sample preparation, transport and storage and, importantly, optimization of validated PCR-based HPV testing platforms for self-collected specimens. Suboptimal rates of clinical follow-up post-SS screening, as well as overtreatment with reliance solely on molecular assays, have both been documented and remain concerning. Therefore, effective strategies are still required to ensure linkage to follow-up testing and management following positive SS results by trained health professionals with knowledge of HPV biology and management algorithms. Because of the prolonged SS screening intervals, implementation data are limited regarding subsequent screening rounds of SS-screened individuals; however, these are accumulating gradually. With further refinement of assays and validation of novel biomarkers in self-collected samples, there is a clear potential for increasing SS accuracy and PPV. The potential differentiation of self-collection protocols for vaccinated versus non-vaccinated individuals also represents an open issue. In conclusion, HPV-based self-collection techniques can effectively address limited uptake alongside other conventional cervical screening drawbacks; however, assays, logistics and infrastructures need further optimization to increase the efficacy, effectiveness and cost-effectiveness of SS approaches.

Delphinidin diminishes in vitro interferon-γ and interleukin-17 producing cells in patients with psoriatic disease.

The anthocyanidin delphinidin reduces psoriasiform lesions and inflammatory mediators in human cell culture systems. Its role in psoriatic disease has not yet been investigated. We assessed delphinidin's in vitro immunomodulatory effect on ex vivo stimulated peripheral blood mononuclear cells (PBMCs) from 50 individuals [26 with psoriasis, 10 with psoriatic arthritis (PsA) and 14 healthy controls (HCs)]. Cells were either left untreated or stimulated with PMA plus ionomycin in the presence or absence of delphinidin. Intracellular production of interferon-γ (IFNγ), interleukin-17A (IL-17A), and interleukin-10 (IL-10) was measured flow cytometrically. Delphinidin dose-dependently reduced IFNγ+ T cells from patients and HCs. The mean IFNγ decrease in CD4+ T subpopulations was 42.5 ± 28% for psoriasis patients, 51.8 ± 21.5% for PsA patients and 49 ± 17% for HCs (p < 0.001 for all). Similarly, IFNγ reduction in CD8+ T cells was 34 ± 21.6% for psoriasis patients, 47.1 ± 22.8% for PsA and 44.8 ± 14.3% for HCs (P < 0.001 for all). An inhibitory effect of delphinidin was also noted in IFNγ producing NKs and NKTs from psoriasis individuals. Delphinidin also significantly decreased IL-17+ CD4+ T cells in all tested subjects, with marginal effect on the increase of IL-10-producing T regulatory subsets. In conclusion, delphinidin exerts a profound in vitro anti-inflammatory effect in psoriasis and psoriatic arthritis by inhibiting IFNγ+ innate and adaptive cells and T helper (Th) 17 cells. If this effect is also exerted in vivo, delphinidin may be regarded as a nutraceutical with immunosuppressive potential.

The Influence of Sexual Behavior and Demographic Characteristics in the Expression of HPV-Related Biomarkers in a Colposcopy Population of Reproductive Age Greek Women.

Despite the significant scientific evolution in primary and secondary cervical cancer prevention in the battle started by George Papanicolaou in the previous century, global cervical cancer mortality rates remain disappointing. The widespread implementation of HPV-related molecular markers has paved the way to tremendous developments in cervical cancer screening, with the transition from cytological approach to the more accurate and cost-effective HPV testing modalities. However, the academic audience and different health systems have not yet adopted a universal approach in screening strategies, and even artificial intelligence modalities have been utilized from the multidisciplinary scientific armamentarium. Combination algorithms, scoring systems as well as artificial intelligent models have been so far proposed for cervical screening and management. The impact of sexual lifestyle inherently possesses a key role in the prevalence of HPV-related biomarkers. This study aimed to investigate any possible influence of sexual behavior and demographic characteristics in the expression of HPV-related biomarkers in a colposcopy population from October 2016 to June 2017, and corroborated the determining role of age at fist intercourse; the older the age, the lower the probability for DNA positivity. Multivariate analysis illustrated additionally that a number of sexual partners exceeding 4.2 was crucial, with women with ≤5 partners being approximately four times less likely to harbor a positive HPV DNA test (p < 0.0001). Similarly, a reported partner change during the last year before HPV DNA assessment contributed to 2.5 times higher odds for DNA positivity (p = 0.0006). From this perspective, the further development and validation of scoring systems quantifying lifestyle factors that could reflect cervical precancer risk seems paramount.

Urine HPV in the Context of Genital and Cervical Cancer Screening-An Update of Current Literature.

Within the previous decades, following the widespread implementation of HPV-related biomarkers and computerization in liquid-based cytology, screening for lower genital tract malignancies has been optimized in several parts of the world. Many organized anogenital cancer prevention systems have reached a point at which efficacy is more a matter of population coverage and less of available infrastructures. Meanwhile, self-sampling modalities in which biologic material (vaginal secretions, urine, etc.) is obtained by the individual and not the clinician and subsequently undergoes examination for HPV biomarkers enjoy appreciating acceptance. Bygone the initial skepticism that vaginal or urine HPV represents "passenger" transient infections, extensive scientific work has been conducted to optimize high-risk HPV (hrHPV) detection from this "novel" biologic material. Nowadays, several state-of-the-art meta-analyses have illustrated that self-sampling techniques involving urine self-sampling represent a feasible alternative strategy with potentially enhanced population coverage possessing excellent performance and sensitivity. Recently published scientific work focusing on urine HPV was reviewed, and after a critical appraisal, the following points should be considered in the clinical application of hrHPV urine measurements; (i) use of first-void urine (FVU) and purpose-designed collection devices; (ii) using a preservation medium to avoid human/HPV DNA degradation during extraction and storage; (iii) using polymerase chain reaction (PCR) based assays, ideally with genotyping capabilities; (iv) processing of a sufficient volume of whole urine; and (v) the use of an analytically sensitive HPV test/recovery of cell-free HPV DNA in addition to cell-associated DNA.