Human papillomavirus and Epstein-Barr virus infection in benign thyroid lesions.

INTRODUCTION: The objective was to investigate the correlation between Epstein-Barr virus (EBV) and human papillomavirus (HPV) infection in the development of benign thyroid lesions. MATERIAL AND METHODS: 29 cases of Hashimoto's thyroiditis (HT), 133 cases of thyroid adenoma, and 34 cases of HT with thyroid adenoma paraffin embedded tissue samples were used for EBV and HPV quantitative detection. RESULTS: None of the tissue samples carried HPV DNA. In HT tissue samples, the positive rate of EBV was 55.2% (16/29). In thyroid adenoma tissue samples, the positive rate was 37.6% (50/133). In HT combined with thyroid adenoma tissue samples, the positive rate of EBV was 67.6% (23/34). There was no correlation between EBV infection and clinical features such as age and gender. CONCLUSION: The occurrence and development of benign thyroid lesions are closely related to EBV infection. HT combined with thyroid adenoma may be more susceptible to EBV infection than simple HT and thyroid adenoma, which provides a new idea for the diagnosis and treatment of benign thyroid lesions.

Sebaceous neoplasms: prevalence of HPV infection and relation to immunohistochemical surrogate markers.

BACKGROUND: Sebaceous neoplasms (SNs) and carcinomas (SCs) represent rare skin adnexal tumours. OBJECTIVES: To establish the prevalence of HPV in SNs, assess the relationship between HPV, p16 and p53 expression, and further elucidate the carcinogenetic course of SCs. MATERIALS & METHODS: A total of 113 resected SNs (five sebaceous adenomas, 10 sebaceomas and 98 SCs) from the Near-East were reviewed. Clinical information (age, gender, size and anatomical location), microscopic variables, and expression of several immunohistochemical markers (EMA, CK5/6, p63, p40, AR, p16 and p53) were documented. Cases were evaluated by fluorescently labelled PCR for HPV detection, followed by DNA microarray hybridization for subtype detection. RESULTS: HPV infection was detected in 9.4% of SNs: 28.6% sebaceous adenomas (HPV-16 and HPV-66), 9.1% sebaceomas (HPV-18) and 8.1% SCs. High-risk HPV types (HPV-16, -18, -52 and -66) constituted 90.9% of HPV infections. Histologically, HPV-positive SCs showed significantly milder cytologic atypia and patchy cellular necrosis. p16 was expressed in SNs irrespective of HPV status (20.0%, 33.3% and 65.5% of HPV-negative sebaceous adenomas, sebaceomas, and SCs, respectively), and p53 was abnormally expressed in 95.5% of HPV-negative SCs and all HPV-positive SCs. CONCLUSION: HPV infection is significantly present in benign and malignant SNs. HPV-positive SCs exhibit less cytologic atypia and necrosis than HPV-negative cases. p16 is not a surrogate marker of HPV infection in the SN setting. Further elucidation of various carcinogenic mechanisms in SCs will allow clinicians to single out the various populations at risk, optimize possible preventive strategies and develop targeted therapies.

Neuro-ophthalmic presentation of COVID-19 disease: A case report.

COVID-19 is a respiratory virus, which has affected various organ systems as well. Here we report a neuro-ophthalmic presentation of pituitary apoplexy under the setting of COVID-19 infection in a middle-aged man who presented to ophthalmic emergency with sudden bilateral loss of vision along with a history of fever past 10 days. There was sluggishly reacting pupils and RT-PCR for COVID was positive. Imaging pointed the diagnosis as pituitary macroadenoma with apopexy. In view of pandemic situation, patient was given symptomatic treatment as per the protocols and stabilized. Vision also showed improvement to some extent and the patient is awaiting neurosurgery.

The prevalence of human papillomavirus in colorectal cancer and adenoma: A meta-analysis.

OBJECTIVE: The objective of this study is to further clarify the correlation between colorectal cancer (CRC) and human papillomavirus (HPV) through literature search and meta-analysis, which is conducive to the formulation of further prevention programs. METHODS: Searching Web of Science, PubMed, MEDLINE, Scopus, and CENTRAL for studies investigating the relationship between CRC and HPV. All analyses were performed through Revman (version 5.3, the Cochrane Collaboration, Oxford, UK). Data from selected studies were extracted into two by two tables. Moreover, all included studies were weighted and summarized. RESULTS: Eighteen studies were included. The expression of HPV in CRC tissues was obviously higher than that in nonmalignant tissues (odds ratio [OR] = 5.56, 95% confidence interval [CI] = 3.18-9.72, Z = 6.02, P < 0.00001). The expression of HPV in CRC tissues and adenoma tissues showed no significant abnormalities (OR = 1.74, 95% CI = 0.92-3.29, Z = 1.70, P = 0.09). The expression of HPV in CRC tissues was obviously higher than that in normal tissues (OR = 7.23, 95% CI = 3.89-13.42, Z = 6.27, P < 0.00001). CONCLUSION: HPV infection in CRC tissues was obviously higher than that in nonmalignant tumor tissues and normal colon tissues, but there were no statistically significant abnormalities between CRC tissues and adenoma tissues.

Multiple Signatures of the JC Polyomavirus in Paired Normal and Altered Colorectal Mucosa Indicate a Link with Human Colorectal Cancer, but Not with Cancer Progression.

The JC polyomavirus (JCV) has been repeatedly but discordantly detected in healthy colonic mucosa, adenomatous polyps, and colorectal cancer (CRC), and proposed to contribute to oncogenesis. The controversies may derive from differences in JCV targets, patient's cohorts, and methods. Studies of simultaneous detection, quantification, and characterization of JCV presence/expression in paired samples of normal/altered tissues of the same patient are lacking. Therefore, we simultaneously quantified JCV presence (DNA) and expression (mRNA and protein) of T-antigen (T-Ag), Viral Protein 1 (Vp1), and miR-J1-5p in paired normal/altered tissues of CRC or polyps, and from controls. JCV signatures were found in most samples. They increased in patients, but were higher in normal mucosa than in corresponding polyp or CRC lesions. JCV non-coding control region (NCCR) DNA rearrangements increased in CRC patients, also in normal mucosa, thus before the onset of the lesion. A new ∆98bp NCCR DNA rearrangement was detected. T-Ag levels were higher in normal mucosa than in adenoma and adenocarcinoma lesions, but decreased to levels of controls in established CRC lesions. In CRC, miR-J1-5p expression decreased with CRC progression. Vp1 expression was not detected. The data indicate a JCV link with the disease, but possible JCV contributes to oncogenesis should occur at pre-polyp stages.

Papillomavirus DNA not detected in canine lobular orbital adenoma and normal conjunctival tissue.

BACKGROUND: Canine lobular orbital adenomas are benign tumors that arise from orbital glandular tissue and extend into the orbit, conjunctiva, and third eyelid. Surgical excision is challenging and recurrence rates are high following excision alone. Enucleation and exenteration reduces the likelihood of recurrence, but is a radical therapeutic option for an otherwise visual and comfortable eye. Human papillomavirus causes 4.5% of worldwide cancers in people and has been identified in up to 23% of benign salivary gland tumors. To date, the etiology of canine lobular orbital adenomas has not been established and it is reasonable to consider canine papillomaviruses as an associative agent with benign glandular tumors in dogs. Identification of the underlying etiology of these tumors may help establish treatment or preventative measures. The purpose of this study was to evaluate conjunctival and orbital tissue of phenotypically normal dogs and tissue from canine lobular orbital adenomas for the presence of papillomavirus DNA. RESULTS: Thirty seven canine lobular orbital adenoma samples (36 formalin fixed paraffin embedded (FFPE) tissue samples from 33 dogs and one freshly collected sample) were evaluated via polymerase chain reaction for the presence of papillomavirus DNA. Conjunctival tissue samples, from 10 dogs with normal ocular examinations, excised immediately following euthanasia, were used as phenotypically normal controls. Three FFPE and one freshly collected tissue samples previously confirmed to be positive for papillomavirus DNA were used as positive controls. PCR products verified positive controls. Papillomavirus DNA was not detected in fresh conjunctival tissue of the phenotypically normal control dogs or in samples of fresh or FFPE canine lobular orbital adenoma tissue. CONCLUSIONS: An association between papillomavirus and the development of canine lobular orbital adenomas is unlikely. Further research is needed to evaluate if other viruses play a role in the pathogenesis of canine lobular orbital adenomas.

Hepatitis B Virus Infection Is Independently Associated With Advanced Colorectal Adenoma.

BACKGROUND: Studies on the association of chronic hepatitis B virus (HBV) infection with colonic neoplasm are rare. We aimed to investigate the association between chronic HBV infection and the development of colonic adenoma. MATERIALS AND METHODS: One hundred thirty-three patients with chronic HBV infection who underwent colonoscopic examination, were enrolled. A healthy HBV-uninfected group was matched with the HBV group. Those with a previous history of colorectal cancer, inflammatory bowel diseases or colorectal surgery were excluded from both HBV and HBV-uninfected groups. Clinical information and data on age, sex, body mass index, smoking, alcohol consumption and comorbidities were obtained. Advanced adenoma was defined as tubular adenoma ≥10mm, or adenoma with a villous component or high-grade dysplasia. RESULTS: The HBV group had a higher rate of colorectal adenoma and advanced adenoma than the HBV-uninfected group. Patients in the HBV group had larger colorectal polyps than those in the HBV-uninfected group. In the chi square test, HBV DNA positivity was significantly associated with colorectal adenoma (P < 0.001) and advanced adenoma (P = 0.007). HBV infection (odds ratio [OR] = 23.961, 95% CI: 9.400-61.076), diabetes mellitus (OR = 2.633, 95% CI: 1.071-6.473) and age (OR = 1.057, 95% CI: 1.020-1.095) were significantly associated with advanced adenoma in the multivariable logistic regression analysis. Multivariable logistic regression analysis within the HBV group revealed that HBV DNA (OR = 1.236, 95% CI: 1.029-1.485) was associated with advanced adenoma. CONCLUSIONS: HBV DNA in patients with HBV infection and HBV infection are independently associated with advanced colorectal adenoma development.

Inflammatory infiltrates in parathyroid tumors.

CONTEXT: Inflammatory infiltrates are sometimes present in solid tumors and may be coupled to clinical behavior or etiology. Infectious viruses contribute to tumorigenesis in a significant fraction of human neoplasias. OBJECTIVE: Characterize inflammatory infiltrates and possible viral transcription in primary hyperparathyroidism. DESIGN: From the period 2007 to 2016, a total of 55 parathyroid tumors (51 adenomas and 4 hyperplasias) with prominent inflammatory infiltrates were identified from more than 2000 parathyroid tumors in the pathology archives, and investigated by immunohistochemistry for CD4, CD8, CD20 and CD45 and scored as +0, +1 or +2. Clinicopathological data were compared to 142 parathyroid adenomas without histological evidence of inflammation. Transcriptome sequencing was performed for 13 parathyroid tumors (four inflammatory, 9 non-inflammatory) to identify potential viral transcripts. RESULTS: Tumors had prominent germinal center-like nodular (+2) lymphocytic infiltrates consisting of T and B lymphocytes (31%) and/or diffuse (+1-2) infiltrates of predominantly CD8+ T lymphocytes (84%). In the majority of cases with adjacent normal parathyroid tissue, the normal rim was unaffected by the inflammatory infiltrates (96%). Presence of inflammatory infiltrates was associated with higher levels of serum-PTH (P = 0.007) and oxyphilic differentiation (P = 0.002). Co-existent autoimmune disease was observed in 27% of patients with inflammatory infiltrates, which in turn was associated with oxyphilic differentiation (P = 0.041). Additionally, prescription of anti-inflammatory drugs was associated with lower serum ionized calcium (P = 0.037). CONCLUSIONS: No evidence of virus-like sequences in the parathyroid tumors could be found by transcriptome sequencing, suggesting that other factors may contribute to attract the immune system to the parathyroid tumor tissue.

Molecular evidence of high-risk human papillomavirus infection in colorectal tumours from Cuban patients

The association between colorectal cancer and human papillomavirus (HPV) infection is still unproven. The aim of this study was to investigate the presence of high-risk HPV (HR-HPV) DNA in colorectal tissues from Cuban patients. A total of 63 colorectal formalin-fixed paraffin-embedded tissues were studied (24 adenocarcinoma, 18 adenoma, and 21 colorectal tissues classified as benign colitis). DNA from colorectal samples was analysed by quantitative real-time polymerase chain reaction to detect the most clinically relevant high HR-HPV types (HPV-16, -18, -31, -33, -45, -52, and -58). Associations between histologic findings and other risk factors were also analysed. Overall, HPV DNA was detected in 23.8% (15/63) of the samples studied. Viral infections were detected in 41.7% of adenocarcinoma (10/24) and 27.7% of adenoma cases (5/18). HPV DNA was not found in any of the negative cases. An association between histological diagnosis of adenocarcinoma and HPV infection was observed (odd ratio = 4.85, 95% confidence interval = 1.40-16.80, p = 0.009). The only genotypes identified were HPV 16 and 33. Viral loads were higher in adenocarcinoma, and these cases were associated with HPV 16. This study provides molecular evidence of HR-HPV infection in colorectal adenocarcinoma tissues from Cuban patients.

Molecular evidence of high-risk human papillomavirus infection in colorectal tumours from Cuban patients.

The association between colorectal cancer and human papillomavirus (HPV) infection is still unproven. The aim of this study was to investigate the presence of high-risk HPV (HR-HPV) DNA in colorectal tissues from Cuban patients. A total of 63 colorectal formalin-fixed paraffin-embedded tissues were studied (24 adenocarcinoma, 18 adenoma, and 21 colorectal tissues classified as benign colitis). DNA from colorectal samples was analysed by quantitative real-time polymerase chain reaction to detect the most clinically relevant high HR-HPV types (HPV-16, -18, -31, -33, -45, -52, and -58). Associations between histologic findings and other risk factors were also analysed. Overall, HPV DNA was detected in 23.8% (15/63) of the samples studied. Viral infections were detected in 41.7% of adenocarcinoma (10/24) and 27.7% of adenoma cases (5/18). HPV DNA was not found in any of the negative cases. An association between histological diagnosis of adenocarcinoma and HPV infection was observed (odd ratio = 4.85, 95% confidence interval = 1.40-16.80, p = 0.009). The only genotypes identified were HPV 16 and 33. Viral loads were higher in adenocarcinoma, and these cases were associated with HPV 16. This study provides molecular evidence of HR-HPV infection in colorectal adenocarcinoma tissues from Cuban patients.

Detection of human papillomavirus infection by molecular tests and its relation to colonic polyps and colorectal cancer.

OBJECTIVES: To prospectively examine the association between human papilloma virus (HPV) colonization of the colonic mucosa and the development of colorectal polyps (CRPs), and colorectal cancer (CRC) in Saudi Arabia. METHODS: A case control study was performed between January 2013 and December 2014. All eligible patients underwent standard diagnostic colonoscopy. Patients with polyps or colorectal cancer were considered cases, while those with any other endoscopic findings were controls. Biopsy samples from polyps and tumors, and/or from normal colonic mucosa were acquired. Human papilloma virus colonization was detected using a hybrid capture technique of samples taken from both normal tissue, and CRPs and CRC. The association between HPV and CRPs/CRC was evaluated. RESULTS: A total of 132 patients were recruited. The mean age was 53 (± 15.9) years. Sixty patients had endoscopically detectable CRPs/CRC, and 72 had either inflammation or normal endoscopic evaluations. Only 4 (0.8%) of the 132 samples that were collected and analyzed were positive for the HPV gene. Statistical analysis did not identify any significant association between HPV colonization and the presence of CRPs/CRC. The only significant predictor of detecting CRPs/CRC on colonoscopy was symptomatic presentation (odds ratio=11.072, 95% confidence interval 4.7-26.2, p less than 0.001). CONCLUSION: Human papilloma virus colonic colonization is rare in Saudi Arabia. An association between HPV colonization and CRP/CRC development could not be identified in this cohort of patients.

Evidence for possible role of toll-like receptor 3 mediating virus-induced progression of pituitary adenomas.

Tumor-related viruses are known to be involved in initiation and progression of certain tumors. However, the relationship between virus and pituitary adenomas (PAs) remains unknown. Here, we investigated infection status of three types of viruses (HPV16, HHV6B and HSV1) and expression level of toll-like receptor 3 (TLR3) in 60 human PA samples. We also determined the role of TLR3 signaling pathway on a PA cell line (GH3). We firstly found that positive rates of HPV16 and HHV6B infection were significantly higher in invasive PA samples than in noninvasive samples (P < 0.01). Similarly, TLR3 mRNA and protein expression also increased in invasive PA samples (P < 0.01). In vitro analysis indicated that GH3 cell proliferation and survival were enhanced by TLR3 activation, which was accompanied by NF-κB activation. Our data indicate that HPV16 and HHV6B viruses may be involved in promoting the progression of PA by activating the TLR3 signaling pathway.

Epstein-Barr virus DNA in colorectal carcinoma in Iranian patients.

Colorectal cancer is an often fatal cancer with a rapidly increasing incidence. Current mortality is estimated to be approximately 600,000 per year, and both environmental and genetic factors are involved in its etiology. Viral and bacterial factors have a proven role in the incidence of approximately 20% of cancers. In the present study, the Epstein-Barr virus (EBV) was detected in 50 colorectal adenocarcinomas, 12 colon adenomas, and 38 control tissue samples using polymerase chain reaction (PCR). Epstein-Barr virus DNA was identified in 19 of the adenocarcinoma tissues, 1 adenoma tissue and 24 control specimens. In total, 15.8% (3/18) of the colorectal samples in the well-differentiated grade, 79% (15/30) in the moderately differentiated, and 5.2% (1/2) in the poorly differentiated grade tested positive for viral infection. Epstein-Barr virus was more prevalent in the moderately differentiated grade. Statistical analysis did not suggest a significant association between EBV and the incidence of colorectal cancer. However, it appears that the virus stimulates progression of the malignancy.

BK polyomavirus-infected nephrogenic adenoma of the urinary bladder in a renal transplant recipient: A case report.

This report describes the morphological and immunohistochemical features of the first case of a nephrogenic adenoma (NA) of the urinary bladder infected with polyomavirus. The findings occurred in a female patient, 6 months post cadaveric renal transplant. Voided urine cytology was positive for decoy cells. Renal transplant biopsy showed no evidence of BKV allograft nephropathy. Cystoscopy demonstrated multiple erythematous patchy and nodular areas. These were found in the left and right posterior wall, and the right lateral wall toward the bladder neck, and were suspicious for either chronic inflammation or neoplasia. Hematoxylin-eosin stained sections showed a NA with scattered pleomorphic nuclei demonstrating smudged chromatin and amorphous basophilic ground glass inclusions. Strong expression of polyomavirus large T antigen (SV40) and VP1 was seen in atypical lesional cells, consistent with cytopathic lytic polyomavirus infection. Positive staining with PAX8 supports the renal cell derivation of NA. The findings in the present case suggest that polyomavirus infection, as an irritant of the bladder mucosa, contributed to the cytologic atypia of infected lesional cells but is not a pathogenic factor of NA.

Activation and regulation of endogenous retroviral genes in the human pituitary gland and related endocrine tumours.

AIMS: Adenohypophysis (AH) hormone-producing cells represent the origin of diverse groups of pituitary adenomas (PA). Deregulation of hypothalamic hormone receptors, growth factors and cAMP signalling have been implicated in the aetiology of PA. Endogenous retroviruses (ERVs) are derived from past exogenous retroviral infections and represent more than 8% of the human genome. Some ERV genes encode open reading frames and produce functional proteins, for example, the ERVW-1 envelope gene Syncytin-1, essential for placentogenesis, but also deregulated in human tumours. Data concerning ERV expression in the AH and related endocrine tumours are missing. METHODS: Syncytin-1 protein was analysed in normal AH (n = 15) and compared with five PA subtypes (n = 117) by immunohistochemistry. Absolute gene expression of 20 ERV functional envelope genes and ERVW-5 gag was measured. PA tissues were examined for Syncytin-1 and the cAMP signalling marker phospho-CREB-Ser133 using immunohistochemistry. Isolated primary human PA cells were treated with different hormones. Murine embryonic and adult pituitary gland ERV expressions were compared with human AH. RESULTS: Syncytin-1 protein colocalized with corticotropic cells of AH. In contrast, all PA demonstrated significant Syncytin-1 protein overexpression, supporting deregulation. All other ERV genes showed significant up-regulations in different PA subtypes. Phospho-CREB-Ser133 and Syncytin-1 colocalized in PA cells. Cultivated primary PA cells with ACTH or CRH induced their respective receptors and ERV genes. Syncytin-A/-B, murine orthologues to human Syncytin-1/-2, localized to embryonic and adult pituitary glands demonstrating functional mammalian conservation. CONCLUSIONS: Deregulated ERV genes may contribute to PA development via cAMP signalling.

Lack of human papillomavirus DNA in colon adenocarcinama and adenoma.

BACKGROUND: Human papilloma viruses (HPV) have been detected in several types of cancers. Over the last few years, a possible correlation between HPV infection and colon cancers has been suggested. The aim of this study was to assess the presence of HPV-DNA in colon adenocarcinomas and adenomas to describe the relationship of HPV infection with these pathologic features. MATERIALS AND METHODS: The study included formalin-fixed and paraffin-embedded tissue samples of 70 patients with colon adenocarcinoma and 30 patients with adenoma (as study group) and 30 tumor adjacent tissues (as control). HPV-DNA was purified and first amplified through MY09/MY11 and GP5+/GP6+ primers. Subsequently, for more precision, another PCR was performed using PGMY09/11 L1 consensus primer system. RESULTS: All tested adenocarcinomas and adenomas as well as normal tumor adjacent tissues were negative for all types of HPV in two PCR assays. CONCLUSION: Our results do not support the relationship between HPV infection and colon carcinoma or adenoma. Attributing a role to the HPV in the etiology of colon carcinogenesis will require further studies.

Detection of human cytomegalovirus in patients with colorectal cancer by nested-PCR.

BACKGROUND: The association of colorectal cancer with human cytomegalovirus (HCMV) is a controversial issue in cancer research. This study aimed to identify the HCMV virus in colorectal cancer tissues and to investigate the association of HCMV with colorectal cancer. In this study, 50 cancer tissue samples and 50 samples without colon cancer were studied in order to identify the HCMV virus through nested-polymerase chain reaction. The virus was identified in 15 cases of colorectal cancer tissues (15/50) and in 5 cases of normal tissues (5/50). Eight cases of adenocarcinoma tissues were in a moderately differentiated stage, and 7 cases had well-differentiated stage tissues that were positive for viral DNA. The findings were statistically evaluated at a significance level of p<0.05. The HCMV virus could play a role in creating malignancy and the progress of cancer through the process of oncomodulation.

No evidence of association between human cytomegalovirus infection and papillary thyroid cancer.

BACKGROUND: Human cytomegalovirus (CMV) has been detected in the thyroid gland and thyroid tumors. CMV infection may activate the mitogen-activated protein kinase pathway, of which aberrant activation is frequently associated with BRAF mutation in papillary thyroid cancer. METHODS: A total of 45 paired tumorous and adjacent non-neoplastic tissue samples, including 5 follicular adenoma and 40 papillary thyroid cancer, were obtained during thyroidectomy. BRAF mutational status was determined using direct sequencing. The presence of CMV DNA was determined using conventional PCR and quantitative real-time PCR. CMV protein in the tissue samples were evaluated with Western blot analysis. RESULTS: BRAF mutation was identified in the cancerous part of 31 (78%) papillary thyroid cancers. Papillary cancer with BRAF mutation was significantly associated with a larger tumor size (P = 0.045), extrathyroidal invasion (P = 0.012), lymph node metastasis (P = 0.008), and a higher TNM stage (P = 0.044). CMV DNA and protein were not detected in any studied samples. CONCLUSIONS: Our results suggest no association between CMV infection and papillary thyroid cancer.

The prevalence of human papillomavirus in colorectal adenomas and adenocarcinomas: a systematic review and meta-analysis.

BACKGROUND: The role of human papillomavirus (HPV) in colorectal cancer has been widely studied with conflicting results. We performed a systematic review and a meta-analysis to estimate the prevalence of HPV in colorectal adenocarcinomas and adenomas, and test the potential association. METHODS: The pooled HPV prevalence was estimated using a random effects model and the I(2) statistic was used to describe the amount of heterogeneity. Potential sources of heterogeneity were evaluated by meta-regression and stratified analyses. For the studies on adenocarcinomas including control tissue, random effects estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Thirty-seven studies were included. Among the 2630 adenocarcinomas, the pooled HPV prevalence was 11.2% (95% CI, 4.9-19.6%) with substantial between-study heterogeneity (I(2)=97.2%). The HPV prevalence varied by geographical region with highest prevalence in South America (45.1%, 95% CI, 21.9-69.4%), Asia (39.2%, 95% CI, 20.3-60.0%) and the Middle East (32.2%, 95% CI, 1.1-79.3%), and by detection method with the highest HPV prevalence in PCR-based studies. In the eight case-control studies, the pooled HPV prevalence was 36.8% (95% CI, 21.3-53.8%) in adenocarcinomas and 1.6% (95% CI, 0.0-9.6%) in controls giving an OR of 6.0 (95% CI, 2.0-17.9%) for the association between HPV and colorectal cancer. Among the 415 adenomas, the pooled HPV prevalence was 5.1% (95% CI, 0.0-17.8%; I(2)=93.7%). CONCLUSIONS: HPV may be associated with a subset of colorectal cancers. Future large-scale multicenter case-control studies with data on risk factors such as lifestyle and sexual behaviour are needed.

Infection and persistence of erythrovirus B19 in benign and cancerous thyroid tissues.

Human erythrovirus B19 (EVB19) is a small, pathogenic DNA virus that has been associated with a wide range of illnesses. The primary site of replication is in bone marrow-derived erythroid progenitor cells, but EVB19 DNA has been detected in a wide range of organs. Recently, studies have linked EVB19 to thyroid cancers and other thyroid diseases. Previous studies from multiple laboratories have detected EVB19 capsid proteins in Graves' disease, Hashimoto's thyroiditis, and thyroid cancer tissues. Data on viral gene expression and mechanism of infection in the thyroid are lacking. To investigate EVB19 infection and persistence in the thyroid, previously archived adult and pediatric tissue sections were examined for EVB19 DNA, RNA, and capsid proteins, as well as EVB19 receptor P-antigen and co-receptor α5ß1 integrin. EVB19 DNA and protein were detected in a majority of tissues examined (87% and 68%, respectively). Detection was similar in adult and pediatric samples. Quantification of viral genomes revealed no significant difference in the amount of viral DNA in benign, cancerous, or metastatic thyroid tissues. EVB19 capsid RNA was detected in 67% of the tissues examined, confirming at least low-level viral gene expression. Immunohistochemical staining for P-antigen and α5ß1 detected the receptor and co-receptor most frequently on normal thyroid epithelial cells. EVB19 capsid staining could be detected in tumors lacking viral receptors. These results suggest that normal thyroid epithelial cells are the initial target for EVB19 infection in the thyroid and allow for continued persistence in both normal and cancerous thyroid tissues.