Immunoexpression pattern of TLR3 and TLR7 in minor salivary gland adenoid cystic carcinoma and its role in prognosis.

OBJECTIVES: Adenoid cystic carcinoma (ACC) of the salivary glands has poor long-term prognosis and a high metastatic rate. Toll-like receptors (TLRs), first-line immune activators, have been associated with both tumor progression and suppression. We aimed to study TLR3 and TLR7 behavior in ACC. MATERIALS AND METHODS: We studied TLR3 and TLR7 immunoexpression of 46 minor salivary gland ACCs diagnosed at the Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland over the period 1974-2012. The associations of TLR3 and TLR7 immunoexpression with clinicopathological factors were evaluated by χ2-test and Fisher's exact test. RESULTS: In the majority of samples, both TLR3 and TLR7 were immunoexpressed in cytoplasm. The immunoexpression was heterogeneous between individual tumors. Stronger TLR7 immunoexpression associated with recurrence rate and poorer disease-specific survival (DSS). TLR3 did not associate significantly with survival although we found an inverse correlation between TLR3 and TLR7 immunopositivity. Hence, when TLR3 immunoexpression was negative or mild, TLR7 immunoexpression was moderate to strong, and vice versa. CONCLUSIONS: TLR3 and TLR7 are immunoexpressed in minor salivary gland ACC. TLR7 is potentially an independent prognostic marker for recurrence rate and DSS.

Appearance and recurrence of odontogenic keratocysts.

OBJECTIVE: The purpose of this study was to evaluate the appearance, histopathological features, and recurrence of odontogenic keratocysts (OKCs) from a large single institute registry over a 36-year period. MATERIALS AND METHODS: A total of 226 cases of OKC were identified in 174 patients over a 36-year period in a single institute in Southwestern Finland. Histological specimens were re-evaluated. The patient's age, sex, location, recurrence, and histopathological features of the OKC were the study variables. RESULTS: OKCs occurred more frequently in men, the mean age was 46 years, and the most frequent site was the lower jaw. Recurrence rate was 21%. Histopathologically, inflammation was present in 95% and satellite cysts in 10% of cases. In patients diagnosed with satellite cysts, OKC recurred in 50% of cases, while the corresponding figure for patients without satellite cysts was 17%. CONCLUSIONS: Compared with the literature, patients were older and inflamed cysts were found more frequently. Satellite cysts occurred only in association with chronic inflammation. Based on the results, regular radiographic evaluation is important among patients aged 10-29 years to detect OKCs and to treat them before enlargement, infection, and inflammation. Satellite cysts should be reported and may be a sign of increased risk of OKC recurrence.

IgG Seroreactivites to Viral Capsid Protein VP1 of JC and BK Polyomaviruses in Children at Early Ages with Special Reference to Parental Cofactors.

BK (BKPyV) and JC (JCPyV) polyomaviruses are widespread in humans. Transmission at an early age and the role of parents in spreading these viruses through the family are incompletely understood. Our aim was to determine the seroprevalence of BKPyV and JCPyV in infants at the age of 1, 2, 6, 12, 24, and 36 months and to assess the frequency of BKPyV and JCPyV seroconversion. A variety of maternal and paternal covariates were also tested as potential predictors of these early childhood infections. We used multiplex serology to analyze antibodies to BKPyV and JCPyV from baseline to 3-year follow-up visits. We observed that there was nearly perfect correlation in BKPyV and JCPyV serum IgG antibody levels between the mother-infant pairs during the first year of the infant's life. No correlation among BKPyV antibody titers were found in father-child pairs, whereas JCPyV antibody levels of the father and child had a significant correlation at the 2-year follow-up visit. BKPyV infection may be associated with a child's predisposition to allergy. In conclusion, after the decay of maternal antibodies, children start to develop their own immunity toward BKPyV and JCPyV, and horizontal transmission of infection in the family can occur.

Human polyomavirus BKPyV and JCPyV serostatus has no impact on women´s human papillomavirus infection outcome.

Introduction: Polyomaviruses have both structural and functional similarities with papillomaviruses. Accordingly, their role in human papillomavirus (HPV) associated malignancies has been studied with conflicting results. Our goal was to disclose any association between BK (BKPyV) and/or JC (JCPyV) polyomavirus serology and HPV data derived from Finnish women (327) in a 6-year prospective follow-up. Methods: Glutathione S-transferase fusion-protein-capture (ELISA) in combination with fluorescent bead technology was used to analyze antibodies to BKPyV and JCPyV. In the longitudinal setting, BKPyV or JCPyV serostatus was related to i) oral- and ii) genital low (LR)- and high risk (HR) HPV DNA detection, iii) HPV16 persistence at both these sites, iv) results of the Pap (Papanicolaou) smear taken at baseline, and v) development of incident CIN (cervical intraepithelial neoplasia) during the follow-up. Results: Being BKPyV or JCPyV seropositive was not significantly associated with HPV seropositivity to either LR- or HR-genotypes, genital- or oral HPV DNA positivity, persistence of genital- or oral HPV16 infection, grade of Pap smear, or development of incident CIN. Discussion: Thus, the present study could not provide any confirmation to the concept that co-infections by HPyV and HPV have interactions that impact on the clinical manifestations or outcomes of HPV infections either in the genital tract or in the oral mucosa.

Optimal sampling and analysis methods for clinical diagnostics of vaginal microbiome.

Next-generation sequencing-based microbiological analysis is a complex way to profile vaginal microbiome samples since each step affects the results gained. Methodologies for sample collection lack golden standards. We compared Puritan DNA/RNA swab (PS) and Copan FLOQ swab (CS) and provided consistent and reliable microbiome profiles analyzed by 16S rRNA gene sequencing. We collected two consecutive vaginal samples utilizing PS with room temperature storing and CS with instant freezing from 26 women. Variable region 4 of bacterial 16S rRNA gene was amplified with single PCR by custom-designed dual-indexed primers and sequenced with Illumina MiSeq system. Read quality control, operational taxonomic unit tables, and alpha and beta diversities analysis were performed, and community richness, diversity, and evenness were evaluated and compared between the two samplings and tests. Nineteen sample pairs produced detectable, intact DNA during the extraction protocol and/or further microbial profiles. Alpha bacterial diversity indices were independent on the collection protocol. No significant statistical differences were found in the measured beta diversity metrics between the collection methods. Of the women, 43% had Lactobacillus-dominated vaginal microbiome profile despite of collection method. Previously reported important vaginal microbiome phyla Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria, and Proteobacteria were present in the sample set although their relative abundances varied among individuals. PS and CS enable constant vaginal microbiota sampling. The PS method with no need for instant freezing is suitable for on-site collections at clinics. Furthermore, it seems to be possible to take two samples instead of one with constant microbiological results.

Seroprevalence of polyomaviruses BK and JC in Finnish women and their spouses followed-up for three years.

BK (BKPyV) and JC (JCPyV) polyomavirus infections are commonly subclinical and known infrequently to cause serious clinical diseases. Longitudinal follow-up studies regarding JCPyV and BKPyV serological outcomes are scanty. We analyzed JCPyV and BKPyV IgG-antibodies in 327 pregnant women and their 132 spouses, enrolled in the longitudinal Finnish Family HPV cohort at Turku University Hospital, Finland. Blood samples taken at baseline, and at 12-, 24-, and 36-month follow-up visits were analyzed for capsid protein VP1-antibodies using multiplex serology. Seroprevalence was constant for both BKPyV and JCPyV across the follow-up, varying between 95-99% and 59-68%, respectively, in women and between 96-97% and 66-72%, respectively, in their spouses. Seroconversion to BKPyV and JCPyV was detected in 15% and 18% of the women and in 13% and 19% of the men, respectively. Waning of BKPyV and JCPyV antibodies was infrequent, present in only 5% of the women (both viruses) and in 1.5% of the male spouses (only BKPyV). The number of lifetime sexual partners (p = 0.038) was lower among JCPyV seropositive men. To conclude, seropositivity to BKPyV and JCPyV is common among marital couples in Finland, with only slight differences between genders. In men, the sexual behavior might be associated with JCPyV seroprevalence.

Men with Crohn's disease may have an increased risk for head and neck squamous cell carcinoma - a nationwide register study.

OBJECTIVE: Our goal was to study inflammatory bowel disease (IBD) patients' risk of head and neck squamous cell carcinoma (HNSCC), compared to general population. MATERIALS AND METHODS: We performed a retrospective nationwide register-based study of Finnish individuals diagnosed with IBD between the years 1995 and 2015. The standardized incidence ratio (SIR) of HNSCC was calculated by comparing the cohort's complementary age-year-sex-person-year incidence to that of the whole Finnish population. RESULTS: About 70,567 patients were diagnosed with IBD (Crohn's disease or ulcerative colitis). Later, 89 of them were diagnosed with HNSCC with mean time of 6.82 years. The incidence of HNSCC was increased in IBD patients compared to the Finnish population expectation (SIR 1.3, 95% CI 1.065-1.614, P = 0.062). When calculating Crohn's disease and ulcerative colitis separately as well as men and women separately, the incidence was particularly increased for men with Crohn's disease (SIR 1.951, 95% CI 1.216-2.935, P = 0.025). CONCLUSION: An increased risk for HNSCC was found in men with Crohn's disease compared to the Finnish population expectations. CLINICAL RELEVANCE: This study provides information that would improve follow-up protocols and treatment guidelines of IBD.

Malignant transformation of oral epithelial dysplasia in Southwest Finland.

Oral epithelial dysplasia (OED) is considered a risk for oral squamous cell carcinoma (OSCC). A meta-analysis estimated a mean malignant transformation rate of 12.1% (95% CI 8.1-17.9). The main target of this study was to define how many OED patients develop OSCC in the hospital district of Southwest Finland. A total of 571 patients diagnosed with OED were identified. Their potential subsequent diagnosis of OSCC was derived from the Finnish Cancer Registry. The risk of OSCC development in OED patients was compared with that of the general population without OED. During a mean follow-up of 5.5 (range 0.1-29.0) years 10.9% of OED patients developed OSCC. OED patients had a 44.7-fold higher risk (95% CI 34.4-56.7) of developing OSCC than the general population. The risk was at its highest within two years of OED diagnosis. OED patients in Southwest Finland have a significantly increased risk of developing OSCC relative to the general population, especially within the first two years of dysplasia diagnosis.

Insulin resistance is associated with poorer verbal fluency performance in women.

AIMS/HYPOTHESIS: Type 2 diabetes is an independent risk factor for cognitive decline. Insulin resistance occurring during midlife may increase the risk of cognitive decline later in life. We hypothesised that insulin resistance is associated with poorer cognitive performance and that sex and APOE*E4 might modulate this association. METHODS: The association of insulin resistance and APOE*E4 genotype on cognitive function was evaluated in a nationwide Finnish population-based study (n = 5,935, mean age 52.5 years, range 30-97 years). HOMA-IR was used to measure insulin resistance. Cognitive function was tested by word-list learning, word-list delayed-recall, categorical verbal fluency and simple and visual-choice reaction-time tests. Linear regression analysis was used to determine the association between HOMA-IR and the results of the cognitive tests. RESULTS: Higher HOMA-IR was associated with poorer verbal fluency in women (p < 0.0001) but not in men (p = 0.56). Higher HOMA-IR was also associated with poorer verbal fluency in APOE*E4 -negative individuals (p = 0.0003), but not in APOE*E4 carriers (p = 0.28). Furthermore, higher HOMA-IR was associated with a slower simple reaction time in the whole study group (p = 0.02). CONCLUSIONS/INTERPRETATION: To our knowledge, this is the first comprehensive, population-based study, including both young and middle-aged adults, to report that female sex impacts the association of HOMA-IR with verbal fluency. Our study was cross-sectional, so causal effects of HOMA-IR on cognition could not be evaluated. However, our results suggest that HOMA-IR could be an early marker for an increased risk of cognitive decline in women.