Publications by authors named "Stina Syrjänen"

147 Publications

Oral Human Papillomavirus Infection in Children during the First 6 Years of Life, Finland.

Emerg Infect Dis 2021 Mar 29;27(3):759-766. Epub 2021 Jan 29.

Human papillomavirus (HPV) infections are found in children, but transmission modes and outcomes are incompletely understood. We evaluated oral samples from 331 children in Finland who participated in the Finnish Family HPV Study from birth during 9 follow-up visits (mean time 51.9 months). We tested samples for 24 HPV genotypes. Oral HPV prevalence for children varied from 8.7% (at a 36-month visit) to 22.8% (at birth), and 18 HPV genotypes were identified. HPV16 was the most prevalent type to persist, followed by HPV18, HPV33, and HPV6. Persistent, oral, high-risk HPV infection for children was associated with oral HPV carriage of the mother at birth and seroconversion of the mother to high-risk HPV during follow-up (odds ratio 1.60-1.92, 95% CI 1.02-2.74). Children acquire their first oral HPV infection at an early age. The HPV status of the mother has a major impact on the outcome of oral HPV persistence for her offspring.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2703.202721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920652PMC
March 2021

Interferon-γ and IL-5 associated cell-mediated immune responses to HPV16 E2 and E6 distinguish between persistent oral HPV16 infections and noninfected mucosa.

Clin Exp Dent Res 2021 Jan 9. Epub 2021 Jan 9.

Department of Oral Pathology and Oral Radiology, Institute of Dentistry, Faculty of Medicine, University of Turku, Turku, Finland.

Objectives: Natural history of human papillomavirus (HPV) infection in the head and neck region is poorly understood, and their impact on collective HPV-specific immunity is not known.

Materials And Methods: In this study, we have performed a systematic analysis of HPV16-specific cell-mediated immunity (CMI) in 21 women with known oral and genital HPV DNA status and HPV serology (Ab) based on 6-year follow-up data. These women being a subgroup from the Finnish Family HPV Study were recalled for blood sampling to be tested for their CMI-responses to HPV16 E2, E6, and E7 peptides.

Results: The results showed that HPV16 E2-specific lymphocyte proliferation was more prevalent in women who tested HPV16 DNA negative in oral mucosa and were either HPV16 seropositive or negative than in HPV16 DNA+/Ab+ women (p = 0.046 and p = 0.035). In addition, the HPV16 DNA-/Ab- women most often displayed E6-specific proliferation (p = 0.020). Proportional cytokine profiles indicated that oral HPV16-negative women were characterized by prominent IFN-γ and IL-5 secretion not found in women with persisting oral HPV16 (p = 0.014 and p = 0.040, respectively).

Conclusions: Our results indicate that the naturally arising immune response induced by oral HPV infections displays a mixed Th1/Th2/Th17 cytokine profile while women with persisting oral HPV16 might have an impaired HPV16-specific CMI, shifted partly toward a Th2 profile, similarly as seen earlier among patients with high-grade genital HPV lesions. Thus, the lack of HPV 16 E2 and E6 specific T memory cells and Th2 cytokines might also predispose women for persistent oral HPV16 infection which might be related to the risk of cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cre2.396DOI Listing
January 2021

Prevalence of human papillomavirus in oral epithelial dysplasia: Systematic review and meta-analysis.

Head Neck 2020 10 23;42(10):2975-2984. Epub 2020 Jun 23.

Danish Cancer Society Research Center, Unit of Virus, Lifestyle and Genes, Copenhagen, Denmark.

The purpose of this systematic review and meta-analysis was to estimate the overall and type-specific prevalence of human papillomavirus (HPV) DNA in oral epithelial dysplasia and assess p16 overexpression in relation to HPV-status. A systematic literature search identified 31 eligible studies (832 cases) evaluating the presence of HPV DNA in oral epithelial dysplasia cases by PCR. Of these, six studies evaluated p16 overexpression in relation to HPV-status. The overall pooled prevalence of HPV DNA in oral epithelial dysplasia was 27.2% (95% CI: 17.6-38.1). We observed substantial interstudy heterogeneity, which could not be explained by differences in continent, tissue type, or severity of epithelial dysplasia. HPV16 was the predominant genotype detected. Moreover, 62.2% of HPV positive and 17.8% of HPV negative oral epithelial dysplasia samples stained intensively positive for p16 . This meta-analysis found that 27% of oral epithelial dysplasia harbor HPV DNA. Whether this represents a transient infection or has a carcinogenic role is unknown.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.26330DOI Listing
October 2020

Comparing serum protein levels can aid in differentiating HPV-negative and -positive oropharyngeal squamous cell carcinoma patients.

PLoS One 2020 15;15(6):e0233974. Epub 2020 Jun 15.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: The surrogate immunohistochemical marker, p16INK4a, is used in clinical practice to determine the high-risk human papillomavirus (HPV) status of oropharyngeal squamous cell carcinomas (OPSCC). With a specificity of 83%, this will misclassify some patients compared with direct HPV testing. Patients who are p16INK4a-positive but HPV DNA-negative, or RNA-negative, may be unsuitable for treatment de-escalation aimed at reducing treatment-related side effects. We aimed to identify cost-effective serum markers to improve decision making for patients at risk of misclassification by p16INK4a alone.

Methods: Serum proteins from pre-treatment samples of 36 patients with OPSCC were identified and quantified using label-free mass spectrometry-based proteomics. HPV-status was determined using p16INK4a/HPV DNA and E6/E7 mRNA. Serum protein expressions were compared between groups of patients according to HPV status, using the unpaired t-test with a Benjamini-Hochberg correction. ROC curves (AUC) were calculated with SPSS (v25).

Results: Of 174 serum proteins identified, complement component C7 (C7), apolipoprotein F (ApoF) and galectin-3-Binding Protein (LGALS3BP) significantly differed between HPV-positive and -negative tumors (AUC ranging from 0.84-0.87). ApoF levels were more than twice as high in the E6/E7 mRNA HPV-positive group than HPV-negative.

Conclusions: Serum C7, ApoF and LGALS3BP levels discriminate between HPV-positive and HPV-negative OPSCC. Further studies are needed to validate these host immunity-related proteins as markers for HPV-associated OPSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233974PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295232PMC
August 2020

Biomaterial and implant induced ossification: in vitro and in vivo findings.

J Tissue Eng Regen Med 2020 08 8;14(8):1157-1168. Epub 2020 Jul 8.

International Clinical Research Center of St. Anne's University Hospital Brno, Brno, Czech Republic.

Material-induced ossification is suggested as a suitable approach to heal large bone defects. Fiber-reinforced composite-bioactive glasses (FRC-BGs) display properties that could enhance the ossification of calvarial defects. Here, we analyzed the healing processes of a FRC-BG implant in vivo from the perspective of material-induced ossification. Histological analysis of the implant, which was removed 5 months after insertion, showed the formation of viable, noninflammatory mesenchymal tissue with newly-formed mineralized woven bone, as well as nonmineralized connective tissue with capillaries and larger blood vessels. The presence of osteocytes was detected within the newly generated bone matrix. To expand our understanding on the osteogenic properties of FRC-BG, we cultured human adipose tissue-derived mesenchymal stromal cells (AD-MSCs) in the presence of two different BGs (45S5 and S53P4) and Al O control. AD-MSCs grew and proliferated on all the scaffolds tested, as well as secreted abundant extracellular matrix, when osteogenic differentiation was appropriately stimulated. 45S5 and S53P4 induced enhanced expression of COL2A1, COL10A1, COL5A1 collagen subunits, and pro-osteogenic genes BMP2 and BMP4. The concomitant downregulation of BMP3 was also detected. Our findings show that FRC-BG can support the vascularization of the implant and the formation of abundant connective tissue in vivo. Specifically, BG 45S5 and BG S53P4 are suited to evoke the osteogenic potential of host mesenchymal stromal cells. In conclusion, FRC-BG implant demonstrated material-induced ossification both in vitro and in vivo.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/term.3056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496445PMC
August 2020

Epstein-Barr virus (EBV) and polyomaviruses are detectable in oropharyngeal cancer and EBV may have prognostic impact.

Cancer Immunol Immunother 2020 Aug 20;69(8):1615-1626. Epub 2020 Apr 20.

Department of Pathology, University of Helsinki and HUS Helsinki University Hospital, P.O. Box 21, 00014 HUS, Helsinki, Finland.

Background: The etiological role of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC) is confirmed. However, the role of other oncoviruses in OPSCC is unknown.

Materials And Methods: A total of 158 consecutive OPSCC patients treated with curative intent were included. DNA extracted from tumor sections was used to detect Epstein-Barr virus (EBV), HPV, and the following polyomaviruses: John Cunningham virus (JCV), Simian virus 40 (SV40), and BK virus (BKV) with PCR. In addition, p16 expression was studied by immunohistochemistry, and EBV-encoded small RNA (EBER) transcripts were localized by in situ hybridization. The effect of viral status on overall survival (OS) and disease-free survival (DFS) was analyzed.

Results: A total of 94/158 samples (59.5%) were HPV-positive, 29.1% contained BKV DNA, 20.3% EBV DNA, 13.9% JCV DNA, and 0.6% SV40 DNA. EBER was expressed only in stromal lymphocytes adjacent to the tumor and correlated with HPV positivity (p = 0.026). p16 expression associated only with HPV. None of the three polyomaviruses had an impact on survival. Patients with EBER-positive but HPV-negative OPSCC had significantly poorer OS and DFS than those with HPV-positive OPSCC and slightly worse prognosis compared with the patients with EBER-negative and HPV-negative OPSCC.

Conclusion: Polyomaviruses are detectable in OPSCC but seem to have no impact on survival, whereas HPV was the strongest viral prognostic factor. EBER expression, as a sign of latent EBV infection, may have prognostic impact among patients with HPV-negative OPSCC. EBER analysis may identify a new subgroup of OPSCCs unrelated to HPV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00262-020-02570-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347695PMC
August 2020

Human papillomavirus prevalence in oral potentially malignant disorders: Systematic review and meta-analysis.

Oral Dis 2021 Apr 30;27(3):431-438. Epub 2020 Mar 30.

Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.

Objectives: We aimed to provide pooled estimates of human papillomavirus (HPV) prevalence in oral potentially malignant disorders (OPMD) and evaluate the impact of presence of epithelial dysplasia.

Methods: We searched PubMed, Embase, and Cochrane Library databases for studies that examined the prevalence of HPV DNA in OPMD tested by polymerase chain reaction (PCR).

Results: Across 52 eligible studies (2,677 cases), we found an overall pooled HPV prevalence of 22.5% (95% confidence interval [CI] 16.6-29.0). Between-study heterogeneity was 93%. When stratified by subgroup, the pooled HPV prevalence in leukoplakia (1,232 cases) was 20.2% (95% CI 11.2-31.1), lichen planus (767 cases) 23.0% (95% CI 15.0-32.2), oral submucous fibrosis (238 cases) 28.6% (95% CI 23.0-34.5), proliferative verrucous leukoplakia (60 cases) 24.7% (95% CI 1.8-62.0), and OPMD unspecified (377 cases) 25.4% (95% CI 16.2-35.8). Information on presence of epithelial dysplasia was available in 19 studies, and the results did not vary substantially between non-dysplastic and dysplastic samples. HPV16 was the predominant genotype among HPV-positive OPMD cases (48.2%, 95% CI 31.4-65.2).

Conclusion: We found a pooled HPV DNA prevalence of 22.5% in OPMD cases with great between-study heterogeneity. The HPV prevalence appeared to be comparable across subgroups and independent of epithelial dysplasia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/odi.13322DOI Listing
April 2021

Composition and maternal origin of the neonatal oral cavity microbiota.

J Oral Microbiol 2019 5;11(1):1663084. Epub 2019 Sep 5.

Department of Paediatrics, University of Turku & Turku University Hospital, Turku, Finland.

The origin of the initial oral microbiota in neonates still remains poorly understood. : The aim of this study was to understand how the maternal microbiota contributes to the initial neonatal oral microbiota. : Twelve mother-neonate pairs with samples from the maternal oral mucosa, uterine cervix and placenta and the neonatal oral cavity immediately after birth were studied. The microbiota composition and diversity were characterized by gene sequencing (V3-V4 region). The microbiota analyses and comparisons were carried out with Calypso software version 8.1 and with SourceTracker 1.0.1. : Samples from the neonatal oral cavity showed moderately high bacterial diversity and low richness. The neonatal oral cavity microbiota seems to share features mainly with the microbes detected in the placenta, followed by the cervical microbiota and the maternal oral microbiota. No statistically significant differences in diversity (Shannon index, p = 0.14), richness (Chao1, p = 0.53) or in microbial composition were observed according to delivery mode. The neonatal oral cavity microbiota is not significantly modulated by the birth canal or maternal oral microbiota but displays clear associations with microbes in the placenta. These results suggest that the neonatal oral microbiota may have a prenatal origin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/20002297.2019.1663084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735328PMC
September 2019

Polyomavirus JCPyV infrequently detectable in adenoid cystic carcinoma of the oral cavity and the airways.

Virchows Arch 2019 Nov 1;475(5):609-616. Epub 2019 Jul 1.

Department of Oral Pathology, University of Turku and Turku University Hospital, Turku, Finland.

Our objective was to assess the presence of three polyomaviruses, namely SV40, JCPyV, and BKPyV, and human papillomaviruses (HPV) in adenoid cystic carcinomas (ACC) of the minor salivary glands (MiSG) in the head and neck region. The study comprised 68 MiSG ACC patients operated during 1974-2012 at the Helsinki University Hospital (Helsinki, Finland). Medical records and 68 histological samples were reviewed. Polyomaviruses were detected with quantitative PCR and the DNA-positive samples were further analyzed for the presence of viral tumor T antigen (T-ag) with immunohistochemistry. HPV genotyping was performed with a Multiplex HPV Genotyping Kit. Only JCPyV DNA was found in ACC samples, being present in 7 (10.3%) out of the 68 samples. The viral load of JCPyV was low varying between 1 to 226 copies/μg DNA. The JCPyV-positive samples originated from trachea (two samples), paranasal sinuses (one), and oral cavity (two). Additionally, JCPyV positivity was found in one lung metastasis of a tracheal tumor and one local disease failure of an oral cavity tumor. Three JCPyV DNA-positive samples showed weak nuclear staining for large T-ag. In conclusion, only JCPyV but not SV40, BKPyV, or HPV was found in ACC from the upper and lower airways. JCPyV copy numbers were low which might support its role as a "hit and run agent" in ACC carcinogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00428-019-02617-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861701PMC
November 2019

High levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) in the serum are associated with poor prognosis in HPV-negative squamous cell oropharyngeal cancer.

Cancer Immunol Immunother 2019 Aug 25;68(8):1263-1272. Epub 2019 Jun 25.

Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and HUS Helsinki University Hospital, P.O.Box 263, 00029 HUS, Helsinki, Finland.

Background: An emerging subset of oropharyngeal squamous cell carcinomas (OPSCC) is caused by HPV. HPV-positive OPSCC has a better prognosis than HPV-negative OPSCC, but other prognostic markers for these two different diseases are scarce. Our aim was to evaluate serum levels and tumor expression of matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and to assess their prognostic role in HPV-positive and HPV-negative OPSCC.

Materials And Methods: A total of 90 consecutive OPSCC patients diagnosed and treated with curative intent at the Helsinki University Hospital between 2012 and 2016 were included. Serum samples were prospectively collected. An immunofluorometric assay and an enzyme-linked immunosorbent assay were used to determine MMP-8 and TIMP-1 serum concentrations, respectively. HPV status of the tumors was determined using a combination of HPV-DNA genotyping and p16-INK4a immunohistochemistry. The endpoints were overall survival (OS) and disease-free survival (DFS).

Results: High TIMP-1 serum levels were strongly and independently associated with poorer OS (adjusted HR 14.7, 95% CI 1.8-117.4, p = 0.011) and DFS (adjusted HR 8.7, 95% CI 1.3-57.1, p = 0.024) among HPV-negative patients; this association was not observed in HPV-positive OPSCC. Although TIMP-1 was immunoexpressed in the majority of the tumor tissue samples, the level of immunoexpression was not associated with prognosis, nor did MMP-8 serum levels.

Conclusion: Our results indicate that serum TIMP-1 levels may serve as an independent prognostic marker for HPV-negative OPSCC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00262-019-02362-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682571PMC
August 2019

In situ hybridization for high-risk HPV E6/E7 mRNA is a superior method for detecting transcriptionally active HPV in oropharyngeal cancer.

Hum Pathol 2019 08 21;90:97-105. Epub 2019 May 21.

Department of Pathology, University of Helsinki and HUS Helsinki University Hospital, P.O.Box 21, FI-00014 HUS, Helsinki, Finland; Research Programs Unit, Translational Cancer Biology, University of Helsinki, P.O.Box 63, FI-00014, Helsinki, Finland.

Current human papillomavirus (HPV) detection methods in oropharyngeal squamous cell carcinoma (OPSCC) have varying sensitivity and specificity. We aimed to compare different HPV-detection methods against the test used in clinical practice, ie, p16 immunohistochemistry (IHC) and to evaluate whether another HPV-detection test additional to p16 IHC would be worthwhile in OPSCC specimens. The study cohort comprised 357 consecutive OPSCC patients during two time periods: 2000-2009 and 2012-2016. From tumor tissue slides, HPV mRNA via in situ hybridization (ISH), HPV DNA via ISH and HPV DNA via polymerase chain reaction (PCR) were detected. The results of these methods were compared with p16 IHC results. Additionally, clinicopathological factors were compared with the methods studied. The sensitivity of HPV mRNA ISH, HPV DNA ISH and HPV DNA PCR were 93.4%, 86.3%, and 83.5%, respectively. The corresponding specificity was 92.4%, 95.3%, and 89.1%, respectively. The negative predictive value for p16 IHC was highest (89.0%) when using mRNA ISH, and followed by DNA ISH (83.5%). ISH for high-risk HPV E6/E7 mRNA was found to be a highly specific and sensitive method for detecting HPV in OPSCC. As p16 protein may be overexpressed due to HPV-independent mechanisms, all p16 IHC-positive OPSCCs should be considered for retesting using mRNA ISH in order to verify transcriptionally active HPV. This is especially critical when considering de-escalated treatment approaches for patients with HPV-positive tumors and still maintaining favorable outcomes for this subgroup of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.humpath.2019.05.006DOI Listing
August 2019

Comparison of multiplex-serology and ELISA based methods in detecting HPV16 L1 antibody responses in paired saliva and serum samples of healthy men.

J Virol Methods 2019 08 17;270:26-33. Epub 2019 Apr 17.

Institute of Dentistry, University of Turku, Lemminkaisenkatu 2, 20520 Turku, Finland; Department of Pathology, Turku University Hospital, Kiinamyllynkatu 4-8, 20521 Turku, Finland.

Human papilloma viruses (HPV) are a common cause of transient infections on mucosal surfaces, also in the oral cavity. Some infections remain persistent and can, especially with high risk HPV genotypes, lead to malignancies in the oral-oropharyngeal area. Our understanding of the natural course of oral HPV infections is limited, and the local host responses are poorly known. In this study we show that anti-HPV16L1 antibodies, the IgA response being most abundant, can be measured in saliva of asymptomatic males. HPV16L1 specific multiplex serology and commercial ELISA methods were compared and also the total salivary IgA levels measured. The total salivary IgA concentrations varied from 36 to 163 μg/ml. All the assays could detect anti-HPV16 IgA from saliva, but the correlation between assays varied from non-significant 0.22 to highly significant 0.81, p < 0.01. Salivary antibody responses did not correlate with the antibody responses detected in serum (Spearman correlations between -0.12 and 0.16) not even after adjusting the specific responses to differences in total IgA in saliva. Only six of 34 individuals were HPV16 DNA positive at the time of the sampling, but interestingly, three out of four with oral HPV16 DNA had salivary anti-HPV16 IgA responses below average. In conclusion, our results show that anti-HPV16 antibodies can be measured from saliva and the salivary response differs from that of serum. Individual differences in total salivary antibody concentrations may affect also the amount of HPV16 specific antibodies in saliva. Furthermore, different assay methods showed different specificities; thus comparisons between studies must be done with care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jviromet.2019.04.007DOI Listing
August 2019

HPV in Head and Neck Carcinomas: Different HPV Profiles in Oropharyngeal Carcinomas - Why?

Acta Cytol 2019 12;63(2):124-142. Epub 2019 Mar 12.

Department of Clinical Research, Biohit Oyj, Helsinki, Finland.

Background: The association of human papillomavirus (HPV) with head and neck squamous cell carcinoma (HNSCC) was first described in 1982-1983 by the authors of this review. Prompted by this discovery 35 years ago, an entirely new field of HPV research has emerged, resulting in a paradigm shift from smoking and alcohol as the only etiological factors to confirmation of HNSCC as an important group of HPV-related human malignancies.

Summary: In this review, the authors first describe the scope (i.e., HNSCC) by the anatomic sites of the tumors. Their important site-specific differences in epidemiology are emphasized, and the misconceptions caused by the adopted practice of pooling all tumors from these divergent anatomic sites as a single entity (HNSCC) are pinpointed. The convincing evidence of the established risk factors (smoking and alcohol) is briefly addressed, before entering in the discussion on the causal role of HPV in HNSCC pathogenesis. The global HPV prevalence in different subsets of HNSCC is summarized using the data extracted from all meta-analyses published since 2010. Of all HNSCC subsets, oropharyngeal SCC has an HPV profile distinct form all the other subsets, and the possible mechanisms explaining this intimate association with HPV are discussed. Key Messages: Recent global trends show a constant increase in HNSCC rates particularly among younger age groups. The evidence on cigarette smoking and alcohol consumption as the prime risk factors of HNSCC is overwhelming. During the past 35 years, however, increasing evidence has accumulated implicating an important causal role of HPV in HNSCC. These data have important clinical implications, HPV detection and tailored treatment strategies for HPV-positive HNSCCs currently being an integral part of the oncological management practices of HNSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000495727DOI Listing
May 2019

Benign proliferative epithelial lesions of oral mucosa are infrequently associated with α-, β-, or γ human papillomaviruses.

Laryngoscope Investig Otolaryngol 2019 Feb 3;4(1):43-48. Epub 2018 Dec 3.

Department of Pathology Turku University Hospital Turku Finland.

Background: Oral papillomas and verruca vulgaris have been associated with human papillomavirus (HPV) infection. However, approximately half of these have remained HPV-negative when tested for mucosal HPV genotypes. In this study, we evaluated presence of α-, β-, and γ-HPVs in benign papillary and verrucous lesions.

Methods: Eighty-three clinical lesions with suspected HPV etiology were analyzed for HPV types of genus α (n = 24), β (n = 46), and γ (n = 52). Immunohistochemistry was used for p16 as a possible surrogate marker of high-risk HPV, accompanied by Ki-67 proliferation marker.

Results: Altogether, α-HPVs were detected in 6.4%, β-HPVs in 2.4%, and γ-HPV in 4.8%. The following genotypes were identified: HPV6, 8, 11, 16, 22, 161, and 170. Neither Ki-67 nor p16 positivity alone were associated with HPV but combined staining showed significant inverse association ( = .042).

Conclusion: HPV infection is found only in a minority of benign verrucous and papillary oral lesions, with the predominance of α-HPVs.

Level Of Evidence: 4.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lio2.222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383307PMC
February 2019

From HPV Infection to Lesion Progression: The Role of HLA Alleles and Host Immunity.

Acta Cytol 2019 15;63(2):148-158. Epub 2019 Feb 15.

Department of Oral Pathology, Institute of Dentistry, Faculty of Medicine, University of Turku, Turku, Finland.

Persistent high-risk human papillomavirus (HPV) infection has been associated with increased risk for cervical precancerous lesions and cancer. The host's genetic variability is known to play a role in the development of cervical cancer. The human leukocyte antigen (HLA) genes are highly polymorphic and have shown to be important risk determinants of HPV infection persistence and disease progression. HLA class I and II cell surface molecules regulate the host's immune system by presenting HPV-derived peptides to T-cells. The activation of T-cell response may vary depending on the HLA allele polymorphism. The engagement of the T-cell receptor with the HPV peptide-HLA complex to create an active costimulatory signal is essential for the activation of the T-cell response. Functional peptide presentation by both HLA class I and II molecules is needed to activate efficient helper and effector T-cell responses in HPV infection recognition and clearance. Some of these HLA risk alleles could also be used as preventive tools in the detection of HPV-induced cervical lesions and cancer. These HLA alleles, together with HPV vaccines, could potentially offer possible solutions for reducing HPV-induced cervical cancer as well as other HPV-related cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000494985DOI Listing
May 2019

Epstein-Barr virus and human papillomaviruses as favorable prognostic factors in nasopharyngeal carcinoma: A nationwide study in Finland.

Head Neck 2019 02 14;41(2):349-357. Epub 2018 Dec 14.

Department of Pathology, University of Turku and Turku University Hospital, Turku, Finland.

Background: Nasopharyngeal carcinoma (NPC) is related to Epstein-Barr virus (EBV) in endemic areas; however, the role of viruses in nonendemic countries is unclear. Our nationwide study investigated the prevalence and prognostic significance of EBV and human papillomaviruses (HPVs) in Finnish NPC tumors.

Methods: We analyzed samples from 150 patients diagnosed between 1990 and 2009. Viral status was determined using EBV and HPV RNA in situ hybridizations, and p16 immunohistochemistry. Patient and treatment characteristics were obtained from patient records.

Results: In our white patient cohort, 93 of 150 (62%) patients were EBV-positive and 21/150 (14%) patients were HPV-positive with no coinfections. Thirty-six (24%) tumors were negative for both viruses. The 5-year disease-specific survival for patients with EBV-positive, HPV-positive, and EBV/HPV-negative tumors was 69%, 63%, and 39%, respectively. In multivariable-adjusted analysis, overall survival was better among patients with EBV-positive (P = .005) and HPV-positive (P = .03) tumors compared to patients with EBV/HPV-negative tumors.

Conclusions: In our low-incidence population, EBV and HPV are important prognostic factors for NPC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.25450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590344PMC
February 2019

HPV infection and bacterial microbiota in breast milk and infant oral mucosa.

PLoS One 2018 5;13(11):e0207016. Epub 2018 Nov 5.

Department of Oral Pathology and Oral Radiology, Institute of Dentistry, Faculty of Medicine, University of Turku, Turku, Finland.

Objective: We investigated the association between bacterial microbiota in breast milk and the infant mouth. The influence of human papilloma virus (HPV) infection on infant oral microbiota was also assessed.

Material And Methods: Altogether 35 breast milk and 35 infant oral samples with known HPV status were selected from the Finnish Family HPV Study cohort. In total, there were 31 mother-infant pairs. The microbiota composition was characterized by 16S rRNA gene sequencing (V3-V4 region).

Results: HPV DNA was present in 8.6% (3/35) of the breast milk and 40% (14/35) of the infant oral samples. Eight shared genera between breast milk and infant oral were found; these included Streptococcus, Staphylococcus, Unclassified Gemellaceae, Rothia, Veillonella, Haemophilus, Propionibacterium and Corynebacterium. HPV status was not associated with either microbiota richness or diversity in the infant mouth. However, the infant oral microbiota clustered in different groups according to HPV status. We detected higher abundance of Veillonella dispar (p = 0.048) at species level in HPV negative infant oral samples. We did not detect differences in the breast milk microbiota composition related to HPV infection due to only three HPV positive milk samples.

Conclusions: HPV infection is associated with distinct oral bacterial microbiota composition in infants. The direction of causality underlying the phenomenon remains unclear.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0207016PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218085PMC
April 2019

Oral manifestations of human papillomavirus infections.

Authors:
Stina Syrjänen

Eur J Oral Sci 2018 10;126 Suppl 1:49-66

Department of Oral Pathology and Oral Radiology, Institute of Dentistry, Faculty of Medicine, University of Turku, Turku, Finland.

Papillomaviruses are one of the oldest viruses known, dating back 330 million years. During this long evolution, human papillomaviruses (HPV) have developed into hijackers of human cellular and immune systems in which they replicate and remain silent. Systematic studies on oral HPV infections and their outcomes are still scarce. Oral HPV infections have been linked to sexual behaviour, but recent evidence supports their horizontal, mouth-to-mouth, transmission. Most HPV infections in infants are acquired vertically from the mother during the intrauterine period, during delivery, or later via saliva. The best-known benign clinical manifestations of HPV infection are oral papilloma/condyloma and focal epithelial hyperplasia. Evidence is emerging which suggests that some oral HPV infections might persist. Persistent HPV infection is mandatory for HPV-associated malignant transformation. However, progression of HPV-induced lesions to malignancy requires additional cofactors. In the early 1980s, we provided the first evidence that a subset of oral cancers and other head and neck cancers might be causally linked to HPV infection. This review summarizes current knowledge on the virus itself, its transmission modes, as well as the full spectrum of oral HPV infections - from asymptomatic infections to benign, potentially malignant oral lesions, and squamous cell carcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/eos.12538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174935PMC
October 2018

NFE2L2/NRF2, OGG1, and cytokine responses of human gingival keratinocytes against oxidative insults of various origin.

Mol Cell Biochem 2019 Feb 20;452(1-2):63-70. Epub 2018 Jul 20.

Institute of Dentistry, University of Turku, Lemminkäisenkatu 2, 20520, Turku, Finland.

Objective: Bacterial or tobacco-related insults induce oxidative stress in gingival keratinocytes. The aim of this study was to investigate anti-oxidative and cytokine responses of human gingival keratinocytes (HMK cells) against Porphyromonas gingivalis lipopolysaccharide (Pg LPS), nicotine, and 4-nitroquinoline N-oxide (4-NQO).

Materials And Methods: HMK cells were incubated with Pg LPS (1 µl/ml), nicotine (1.54 mM), and 4-NQO (1 µM) for 24 h. Intracellular and extracellular levels of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1Ra), IL-8, monocyte chemoattractant protein (MCP)-1, and vascular endothelial growth factor (VEGF) were measured with the Luminex® xMAP™ technique, and nuclear factor, erythroid 2 like 2 (NFE2L2/NRF2) and 8-oxoguanine DNA glycosylase (OGG1) with Western blots. Data were statistically analyzed by two-way ANOVA with Bonferroni correction.

Results: All tested oxidative stress inducers increased intracellular OGG1 levels, whereas only nicotine and 4-NQO induced NFE2L2/NRF2 levels. Nicotine, 4-NQO, and their combinational applications with Pg LPS induced the secretions of IL-1β and IL-1Ra, while that of IL-8 was inhibited by the presence of Pg LPS. MCP-1 secretion was suppressed by nicotine, alone and together with Pg LPS, while 4-NQO activated its secretion. Treatment of HMK cells with Pg LPS, nicotine, 4-NQO, or their combinations did not affect VEGF levels.

Conclusion: Pg LPS, nicotine, and 4-NQO induce oxidative stress and regulate anti-oxidative response and cytokine expressions in human gingival keratinocytes differently. These results may indicate that bacterial and tobacco-related insults regulate distinct pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11010-018-3412-yDOI Listing
February 2019

Drug-Sensitivity Screening and Genomic Characterization of 45 HPV-Negative Head and Neck Carcinoma Cell Lines for Novel Biomarkers of Drug Efficacy.

Mol Cancer Ther 2018 09 3;17(9):2060-2071. Epub 2018 Jul 3.

Research Programs Unit, Genome-Scale Biology Program and Medicum, Biochemistry and Developmental Biology, University of Helsinki, Helsinki, Finland.

There is an unmet need for effective targeted therapies for patients with advanced head and neck squamous cell carcinoma (HNSCC). We correlated gene expression, gene copy numbers, and point mutations in 45 human papillomavirus-negative HNSCC cell lines with the sensitivity to 220 anticancer drugs to discover predictive associations to genetic alterations. The drug response profiles revealed diverse efficacy of the tested drugs across the cell lines. Several genomic abnormalities and gene expression differences were associated with response to mTOR, MEK, and EGFR inhibitors. and were the most commonly mutated genes after and also showed some association with response to MEK and/or EGFR inhibitors. amplification and overexpression associated with sensitivity to EGFR inhibitors, and deletion with poor sensitivity to MEK inhibitors. The connection between high expression and responsiveness to the EGFR inhibitor erlotinib was validated by gene silencing and from the data set at the Cancer Cell Line Encyclopedia. The data provide several novel genomic alterations that associated to the efficacy of targeted drugs in HNSCC. These findings require further validation in experimental models and clinical series. .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1535-7163.MCT-17-0733DOI Listing
September 2018

HPV infection and bacterial microbiota in the placenta, uterine cervix and oral mucosa.

Sci Rep 2018 06 28;8(1):9787. Epub 2018 Jun 28.

Department of Oral Pathology and Oral Radiology, Institute of Dentistry, Faculty of Medicine, University of Turku, Turku, Finland.

We investigated the association between HPV infection and bacterial microbiota composition in the placenta, uterine cervix and mouth in thirty-nine women. HPV DNA genotyping of 24 types was conducted using Multimetrix. Microbiota composition was characterized by 16S rRNA gene sequencing. HPV DNA was detected in 33% of placenta, 23% cervical and 33% oral samples. HPV16 was the most frequent type in all regions. HPV infection was associated with higher microbiota richness (p = 0.032) in the mouth but did not influence microbial diversity or richness in other samples. HPV infection was associated with higher abundance of Lactobacillaceae (p = 0.0036) and Ureaplasma (LDA score > 4.0, p < 0.05) in the placenta, Haemophilus (p = 0.00058) and Peptostreptococcus (p = 0.0069) genus in the cervix and Selenomonas spp. (p = 0.0032) in the mouth compared to HPV negative samples. These data suggest altered bacterial microbiota composition in HPV positive placenta, cervix and mouth. Whether the changes in bacterial microbiota predispose or result from HPV remains to be determined in future studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-27980-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023934PMC
June 2018

Polyomaviruses detectable in head and neck carcinomas.

Oncotarget 2018 Apr 27;9(32):22642-22652. Epub 2018 Apr 27.

Department of Oral Pathology and Oral Radiology, Institute of Dentistry, Faculty of Medicine, University of Turku, 20520 Turku, Finland.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.25202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5978254PMC
April 2018

HLA-G and vertical mother-to-child transmission of human papillomavirus infection.

Hum Immunol 2018 Jun 12;79(6):471-476. Epub 2018 Mar 12.

Department of Oral Pathology and Radiology, University of Turku, Lemminkäisenkatu 2, 20520 Turku, Finland; Department of Pathology, Turku University Hospital, Kiinanmyllynkatu 10, 20520 Turku, Finland. Electronic address:

Role of host factors in transmission of human papillomavirus (HPV)-infection from mother to her offspring is not known. Our aim was to study whether human leukocyte antigen (HLA)-G allele concordance among the mother-child pairs could facilitate vertical transmission of HPV, because HLA-G may contribute to immune tolerance in pregnancy. Altogether, 310 mother-child pairs were included from the Finnish Family HPV study. Overall, nine different HLA-G alleles were identified. The HLA-G genotype concordance of G01:01:01/01:04:01 increased the risk of high risk (HR)-HPV genotype positivity in cord blood and infant's oral mucosa. The mother-child concordance of G01:01:02/01:01:02 increased the risk of oral HPV positivity with HR-HPV genotypes both in the mother and offspring; OR 2.45 (95%CI 1.24-4.85). Discordant HLA-G allele for G01:04:01 and for G01:06 was significantly associated with infant's oral low risk (LR)-HPV at birth, OR 3.07 (95%CI 1.01-9.36) and OR 5.19 (95%CI 1.22-22.03), respectively. HLA-G had no association with HPV genotype-specific concordance between the mother and child at birth nor influence on perinatal HPV status of the child. Taken together, our results show that HLA-G molecules have a role in predicting the newborn's likelihood for oral HPV infection at birth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.humimm.2018.03.002DOI Listing
June 2018

Eosinophilia is a favorable prognostic marker for oral cavity and lip squamous cell carcinoma.

APMIS 2018 Mar;126(3):201-207

Department of Oral Pathology and Oral Radiology, Institute of Dentistry, Faculty of Medicine, University of Turku, Turku, Finland.

Eosinophils are frequently encountered with squamous cell carcinomas (SCC) and it has been proposed that tumor-associated tissue eosinophilia (TATE) could be of prognostic significance in oral SCC. The aim was to evaluate TATE in 83 oral cavity and 16 lip SCCs as well as the best possible use of TATE as a prognostic marker. The number of eosinophils was counted per high power fields (HPF, ×400) in three different representative areas of the tumor and its stroma. The degree of TATE was analyzed in relation to clinicopathological features of tumors and patients' survival (follow-up mean 40.7 months) using Fisher's exact test. TATE was detected in 58 (70%) oral and 8 (50%) lip SCC samples. The median number of eosinophils between oral and lip SCC was different (p = 0.028) but TATE was similar per HPF (p = 0.085). Totally, 6% of lip and 21% of oral SCC patients died during the follow-up. The patients with the higher TATE had significantly better survival than the patients with the lower TATE (p = 0.0136). The best cut-off value predicting the survival was 4 eosinophils/HPF. TATE is a prognostic marker for oral and lip SCC: more than 4 eosinophils/HPF may predict more favorable prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apm.12809DOI Listing
March 2018

Presenting symptoms and clinical findings in HPV-positive and HPV-negative oropharyngeal cancer patients.

Acta Otolaryngol 2018 05 21;138(5):513-518. Epub 2017 Nov 21.

a Department of Otorhinolaryngology - Head and Neck Surgery , University of Helsinki and Helsinki University Hospital , Helsinki , Finland.

Objectives: Oropharyngeal squamous cell carcinoma (OPSCC) is divided in two different disease entities depending on HPV involvement. We investigated differences in presenting symptoms and clinical findings in patients with HPV-positive and -negative OPSCC tumors.

Methods: Altogether 118 consecutive patients diagnosed with primary OPSCC between 2012 and 2014 at the Helsinki University Hospital were included. HPV-status of the tumors was assessed by PCR detection of HPV DNA and immunostaining with p16-INK4a antibody.

Results: Fifty-one (47.7%) of the patients had HPV-positive and 56 (52.3%) HPV-negative tumors. Forty-nine (49/51, 96.1%) of the HPV+ tumors were also p16+ showing high concordance. The most common presenting symptom among HPV+/p16+ patients was a neck mass (53.1%), whereas any sort of pain in the head and neck area was more frequently related to the HPV-/p16- (60.0%) group. HPV+/p16+ tumors had a tendency to locate in the tonsillar complex and more likely had already spread into regional lymph nodes compared with HPV-/p16- tumors. Smoking and heavy alcohol consumption were significantly more common among HPV−/p16− patients but also rather common among HPV+/p16+ patients [corrected].

Conclusions: This analysis of symptoms and signs confirm that OPSCC can be dichotomized in two distinct disease entities as defined by HPV status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00016489.2017.1405279DOI Listing
May 2018

Persistent Oral Human Papillomavirus (HPV) Infection is Associated with Low Salivary Levels of Matrix Metalloproteinase 8 (MMP-8).

J Clin Virol 2017 12 23;97:4-9. Epub 2017 Oct 23.

Department of Oral Pathology and Oral Radiology, Institute of Dentistry and MediCity Research Laboratory, University of Turku, Turku, Finland.

Background: A persistent human papillomavirus (HPV) infection is a prerequisite for a HPV related cancer to develop. Asymptomatic, persistent HPV infections are not only found in genital tract, but also on oral mucosa. Oral HPV persistence may be associated with behavioural factors, but data on the role of innate immunity in oral HPV infections are still limited.

Objectives: Salivary concentrations of matrix metalloproteinases MMP-8 and MMP-9, tissue inhibitor of MMPs (TIMP-1), myeloperoxidase, and serum concentrations of MMP-8 were analysed in women with a persistent oral HPV infection and, as a control, in women who remained HPV DNA-negative during a 6-year follow-up. The effects of smoking, lactation and alcohol use on the salivary and serum parameters were assessed, too.

Study Design: A nested case-control setting was used to select a subgroup of 57 women with a persistent oral HPV infection and 102 controls from the Finnish Family HPV Study.

Results: The salivary MMP-8/TIMP-1 molar ratio was lower in HPV DNA-positive women than in controls (p=0.036). The difference was more pronounced in non-smoking women, in this group also the salivary MMP-8 levels differed (p=0.047). There was a correlation between the salivary concentrations of myeloperoxidase and MMP-8 (r=0.567, p<0.001) or MMP-9 (r=0.234, p=003), but no correlation between salivary and serum MMP-8 levels. The MMP-9 concentration and the MMP-9/TIMP-1 molar ratio were significantly lower in smokers than in non-smokers (p=0.020 and p=0.003, respectively).

Conclusions: Persistent oral HPV infection was associated with a low salivary MMP-8 concentration indicating eventually a failure in oral anti-inflammatory defence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcv.2017.10.011DOI Listing
December 2017

17β-estradiol and progesterone effect on human papillomavirus 16 positive cells grown as spheroid co-cultures.

Cytotechnology 2018 Feb 5;70(1):235-244. Epub 2017 Oct 5.

Department of Oral Pathology and Oral Radiology, Institute of Dentistry and MediCity Research Laboratory, Faculty of Medicine, University of Turku, Lemminkäisenkatu 2, 20520, Turku, Finland.

Human papillomavirus (HPV) is the key epidemiologic factor of cervical cancer, but additional cofactors are mandatory. Estrogen has been considered as one of those. Here, the aim was to study the effects of steroid hormones on HPV16 E6-E7, estradiol receptors ERα and ERβ, and progesterone receptor (PR) in HPV16-positive cervical carcinoma cell lines SiHa and CaSki grown as epithelial and fibroblast spheroid co-cultures. The spheroid co-cultures were exposured to 17β-estradiol or progesterone from day 7 onwards. mRNA levels of HPV16 E6-E7, ERα, ERβ and PR normalized against GAPDH were analyzed with quantitative reverse transcription-qPCR (RT-qPCR). 17β-estradiol and progesterone decreased HPV16 E6-E7 mRNA expression in CaSki and increased in SiHA co-cultures. In CaSki co-cultures, ERβ expression was blocked after 17β-estradiol exposure while in SiHa cells it slightly increased ERβ expression. PR expression was seen only in CaSki spheroids and it vanished after exposure to steroid hormones. Fibroblasts expressed all three hormone receptors as monolayers but ERβ expression decreased and ERα and PR vanished after co-culturing. Cell culturing platform changes both oncogene and hormone receptor expression in HPV16 positive cervical cancer cell lines. This needs to be considered when in vitro results are extrapolated to in vivo situations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10616-017-0137-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809654PMC
February 2018

Herpes simplex and human papilloma virus coinfections in oral mucosa of men-A 6-year follow-up study.

J Med Virol 2018 03 20;90(3):564-570. Epub 2017 Oct 20.

Faculty of Medicine, Department of Oral Pathology, Institute of Dentistry, and Medicity Research Laboratory, University of Turku, Turku, Finland.

Herpes simplex virus (HSV) establishes latency in neurons and recurrent infections in oral mucosa. This prospective study analyzes HSV prevalence in oral mucosal brush samples from men with known human papillomavirus (HPV) status. We hypothesized that HSV-1-infection could facilitate HPV persistence as a cofactor. This study was a part of the Finnish Family HPV study accomplished at the University of Turku/Turku University Hospital, Finland. A total of 139 men (mean age 28.6 ± 4.9 years) were enrolled at 36+-weeks of their partner's pregnancy and thereafter followed-up for 6 years. Altogether, 722 samples, extracted from oral brush samples collected at the enrollment timepoint (baseline) and at 2-, 6-, 12-, 24-, 36-month, and 6 years, were available. HSV DNA was analyzed with quantitative PCR. HSV-1 results were compared with the known HPV data. The prevalence of oral HSV-1 shedding varied between 0-7.2% (mean 2.8%) among the men. Mean copy numbers varied between 4 and 550 genome copies/sample. A total of 18 (12.9%) men were found HSV-1-positive at least once, two of them twice. Neither smoking nor oral sex was associated with the oral HSV-1-DNA finding. HPV/HSV-1 co-infection was found in 6 (4.3%) men, all of them having persistent HPV-infection. In conclusion, HSV-1 and its coinfection with HPV in oral mucosa was rare.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmv.24965DOI Listing
March 2018

Breast Milk Is a Potential Vehicle for Human Papillomavirus Transmission to Oral Mucosa of the Spouse.

Pediatr Infect Dis J 2017 07;36(7):627-630

From the *Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland; †Department of Oral Pathology and Radiology, University of Turku, Turku, Finland; ‡Department of Obstetrics and Gynecology, Turku University Hospital, University of Turku, Turku, Finland; §Department of Clinical Research, Biohit Oyj, Helsinki, Finland; and ¶Department of Pathology, Turku University Hospital, Turku, Finland.

Background: Human papillomavirus (HPV) DNA has been detected in breast milk, but its origin has remained obscure. The aim of the study was to analyze the prevalence and persistence of HPV in breast milk in the Finnish Family HPV cohort study. The association of breast milk HPV positivity with the family members' oral HPV status was evaluated.

Methods: We included 308 families to the study where the mother was breast feeding her offspring. Mothers collected the milk samples manually at day 3, and at months 2, 6 and 12. Cervical and/or oral samples were collected from all family members. HPV testing was performed using nested polymerase chain reaction and Luminex-based Multimetrix kit.

Results: Breast milk HPV DNA was found in 10.1% (31/308), 20.1% (39/194) and 28.8% (17/59) of samples at day 3, months 2 and 6, respectively. The following HPV genotypes were detected: 6, 16, 18, 33, 45, 53, 56, 59, 66 and 82. Breast milk HPV persisted among 5.5% (9/164) of the lactating mothers. No significant associations were detected between the persistent breast milk HPV and the offspring's oral incident HPV infection. Breast milk HPV positivity showed a strong association with the fathers' oral HPV positivity at baseline, as well as at 6- and 12-month follow-up visits, with odds ratio (OR) = 3.24 [95% confidence interval (CI): 1.04-10.12], OR = 6.34 (95% CI: 1.84-21.89) and OR = 14.25 (95% CI: 1.16-174.80), respectively.

Conclusions: HPV in breast milk is prevalent among the lactating mothers and HPV can also persist in breast milk. The breast milk is a potential vehicle for HPV transmission to oral mucosa of the spouse but not of the offspring.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/INF.0000000000001546DOI Listing
July 2017

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

Oncotarget 2017 04;8(16):27328-27338

Department of Oral Pathology, Institute of Dentistry, University of Turku, Turku, Finland.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.16033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5432338PMC
April 2017