The clearance of oral high-risk human papillomavirus infection is impaired by long-term persistence of cervical human papillomavirus infection

AbstractPersistence of high-risk (HR-) human papillomavirus (HPV) infection of the uterine cervix increases the risk of cervical cancer. Oral HPV infections are among potential covariates of long-term genotype-specific persistent cervical HR-HPV infections. It is not known whether this persistence reflects inability of the host to reject HPV infections in general. A case–control setting was designed to estimate the covariates of long-term persistent cervical HR-HPV infections using multivariate generalized estimating equation (GEE) models. HPV was detected with PCR using GP05+/GP06+-primers and genotyped for 24 HPVs with a Multimetrix-kit. The cases (n = 43) included women who had genotype-specific persistent cervical HR-HPV infection for at least 24 months (24M+) and controls were women who tested repeatedly HPV-negative in their cervical samples (n = 52). These women represent a sub-cohort of the Finnish Family HPV Study. The cases differed significantly from the HPV-negative controls in several aspects: they were younger, had a longer mean time to incident oral HPV infection (40.7 versus 23.6 months), longer duration of oral HPV persistence (38.4 versus 14.1 months), and longer time to clearance of their oral HPV infection (50.0 versus 28.2 months). In multivariate GEE analysis, the second pregnancy during the follow up was the only independent predictor with significant protective effect against 24M+ persistent cervical HR-HPV infections, OR of 0.15 (95% CI 0.07–0.34). To conclude, long-term persistent cervical HR-HPV infections are associated with a prolonged clearance of oral HR-HPV infections while new pregnancy protects against persistent cervical HR-HPV infections

Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) associated with poor prognosis of head and neck carcinomas

BACKGROUND: Epstein-Barr virus (EBV) is the main cause of nasopharyngeal carcinoma (NPC), also found in other head and neck carcinomas (HNSCCs) where its role remains controversial.RESULTS: EBV was found in 80% and 21% of the samples with PCR and ISH (in cancer cells), respectively. Eight of ISH-positive samples were not NPCs. EBER-RNA detection in carcinoma cells was associated with worse prognosis, whether or not NPCs were included. HPV/EBV and HSV/HPV coinfections associated with a shorter survival. LMP-1 expression, positive in 51% of samples did not correlate with the disease outcome.MATERIALS AND METHODS: We analyzed EBV in 73 HNSCC samples with a known HPV and HSV-1 status, using in situ hybridization (ISH) and immunohistochemistry (IHC) for EBV-early transcripts (EBER) and LMP-1 protein, respectively. EBV-DNA was detected with a Luminex-based method. The results were correlated with HPV-status and disease outcome.CONCLUSIONS: EBV is transcriptionally active in NPC cells but also in a subgroup of other HNSCCs.</p

Polyomaviruses detectable in head and neck carcinomas

Polyomaviruses (PyV) independent or jointly with human papillomavirus (HPV), might have a role in head and neck carcinomas (HNSCC). We analyzed the prevalence and viral DNA loads of SV40, JCV and BKV with quantitative PCR (qPCR) and all 13 HPyVs with a novel Multiplex method in 82 HNSCC samples with known HPV status and disease-specific survival (DSS) and 24 HNSCC cell lines.JCV was the most prevalent PyV present in 37% of HNSCC and the most prevalent sites were lip (80%), larynx (67%) and oral cavity (59%). JCV viral load was highest in larynx but variation was wide (152514 mean copies/μg DNA, SD± 304820). BKV was found only in one oral carcinoma with low viral load. SV40 was detected in 60% lip and 20.7% oral carcinomas with low copy numbers (6.6- 23.7 copies/μg DNA). Altogether, 86% of JCV-positive samples were co-infected with HPV (p=0.001), with no impact on DSS. Agreement between qPCR and Multiplex methods was substantial (Cohen's kappa= 0.659). Multiplex method detected additional HPyV in five samples. JCV was found in 9/24 HNSCC cell lines, all deriving from oral cavity. Our data provide evidence that JCV might have a role in HNSCC as independent virus or co-factor of HPV.</p

End-of-life decisions guiding the palliative care of cancer patients visiting emergency department in South Western Finland: A retrospective cohort study

BackgroundUntil recently, palliative care (PC) resources in Finland have been sparse. To meet the increasing need for PC an end-of-life (EOL) care project has been ongoing in South Western Finland since 2012, and in 2015, a weekday palliative outpatient clinic was established in Turku University Hospital (TUH). The aim of this study was to explore the effect of the project and the PC clinic on the management practices of EOL cancer patients attending the Emergency Department (ED) of TUH from 2013 to 2016.MethodsThe medical records of all cancer patients (ICD-10 codes C00–97) admitted to the ED of TUH between August 1–December 31, in 2013 and 2016, were analyzed: n = 529, n = 432 respectively (2013 and 2016). The analysis focused on those patients in EOL care; n = 77, n = 63, respectively. The late palliative patients were defined by PC decision, thus termination of life-prolonging cancer-specific treatments. The EOL patients were in the imminently dying phase of their illness. The site of referral after an ED visit was also verified together with the documentation on advance care plans (ACP), and the impact of palliative outpatient visits.ResultsIn 2016, the number of late palliative and EOL patients admitted to the ED has shown a tendency to decrease. The quality of the documentation for treatment goals, do-not-resuscitate (DNR) orders, living wills and connections to primary care providers has improved since 2013. Prior visits to palliative outpatient clinic correlated well with the more comprehensive ACP information: i) DNR order (p = 0.0001); ii) connection to primary care (p = 0.003); iii) documented ICD-10 code Z51.5 (p = 0.0001).ConclusionsEven modest investments in resources for PC can induce an objective change in the allocation of health care resources, and improve the ACP for the cancer patients at their EOL. A visit to a palliative outpatient clinic may offer one approach for improving the quality and completion of ACP documentation.</div

Human papillomavirus testing as an optional screening tool in low-resource settings of Latin America: experience from the Latin American Screening study

Hybrid capture II (HC II) test for oncogenic human papillomaviruses (HPV) was carried out in a cohort of 4284 women at their first clinical visit. Overall prevalence of HPV was 17.1%, decreasing with age from 33.9% among women below 20 years to only 11.0% among those older than 41 years. HPV prevalence was significantly higher among current smokers (odds ratio [OR] ¼ 1.31; 95% CI 1.1–1.6), in women with two or more lifetime sexual partners (OR ¼ 1.9; 95% CI 1.6–2.4), and those women with two or more sexual partners during the past 12 months prior to examination (OR ¼ 1.6; 95% CI 1.2–2.2). HPV detection increased in parallel with increasing cytologic abnormality, being highest in women with high-grade squamous intraepithelial lesion (P ¼ 0.001). Specificity of the HPV test in detecting histologically confirmed cervical disease was 85% (95% CI 83.9–86.1). Sensitivity of the HPV test in detecting histologic abnormalities increased in parallel with disease severity, ranging from 51.5% for cervical intraepithelial neoplasia (CIN) 1 to 96.5% for CIN 3 and 100.0% for cancer, with respective decline of positive predictive value. These data suggest that HPV testing with HC II assay might be a viable screening tool among this population with relatively high prevalence of cervical disease