Human papilloma virus infection in vaginal condyloma acuminatum

The objective of this study was to determine the prevalence of human papillomavirus(HPV) infection in vaginal papillomatous lesions diagnosed in Tsuji Ladies Clinic. From January, 2000 to February, 2001, 52 patients were diagnosed with condyloma acuminata in the Clinic. All the patients received a complete gynecologic examination including colposcopic evaluation, and HPV DNA was assayed for in cervicovaginal lavages using polymerase chain reaction. HPV was detected in 31 of the 52 (60%) patients, and high risk HPV was found in 23 patients(45%). The incidence of high risk HPV infection is very high in vaginal condyloma acuminata. Detection of high risk HPV-positive women suggests that they may also be at risk for developing carcinoma. Therefore, it is very important to follow-up patients with condyloma acuminata.     

P53 overexpression and Epstein-Barr virus infection in undifferentiated and squamous cell nasopharyngeal carcinomas

We have analysed 22 nasopharyngeal carcinomas (NPCs) for expression of the small nuclear Epstein-Barr virus (EBV)-encoded RNAs (EBERs) and for immunohistologically detectable overexpression of p53. in situ hybridization demonstrated expression of the EBERs in 13 undifferentiated NPCs while nine squamous cell NPCs were EBER-negative. These results therefore confirm our previous DNA-DNA in situ hybridization studies and demonstrate that in the nasopharynx EBV is exclusively associated with undifferentiated but not with squamous cell carcinomas. p53 overexpression was demonstrated by immunohistology in 5 of 9 squamous cell NPCs and in 9 of 13 undifferentiated NPCs. Thus, there appears to be no correlation of p53 overexpression with EBV infection. These results are unexpected in the light of previous studies demonstrating that the p53 gene in primary undifferentiated NPC is consistently in the wild-type configuration. By contrast, analyses of squamous cell carcinomas of the head and neck have demonstrated that p53 overexpression in these cases is the result of p53 gene mutation. Whilst more detailed genetic analysis is required, our results suggest that mechanisms other than mutation of the p53 gene may be responsible for the stabilization of the protein in cases of undifferentiated NPC. It is tempting to speculate that an EBV-encoded protein may be involved.     

人乳头瘤病毒感染与人乳头瘤病毒疫苗的研究进展

人乳头瘤病毒(HPV)感染与宫颈癌的发生密切相关,是宫颈癌发生的最主要诱发因素.预防性HPV疫苗是一种预防宫颈癌的新方法,其效果得到了多项临床试验的肯定.治疗性HPV疫苗的研发同样备受关注,目前治疗性疫苗的类型很多,但因其机制较复杂,大多仍处在实验阶段.     

Human fibroblast interferon in cervical and vulvar intraepithelial neoplasia associated with papilloma virus infection

The follow-up is presented for 13 patients with cervical intraepithelial neoplasia (CIN) grade II-III and vulvar intraepithelial neoplasia (VIN) grade III associated with papilloma virus infection, treated with human fibroblast interferon. Treatment consisted of 2-3 X 10(6) IU interferon per day injected intra- and peri-lesionally for five days per week for 2-3 weeks, with or without a cream topically applied at the dose of 1.2 X 10(6) IU/day X five days. Among the 13 patients with CIN and VIN, 7 complete (54%) and 2 partial regressions were observed. The duration of response appeared to be between 2 and 14 months. Fever, chills and fatigue were the tolerable side-effects. Our results indicate that treatment with interferon is active against CIN and VIN associated with papilloma virus infection.     

Response of nasopharyngeal carcinoma cells to Epstein-Barr virus infection in vitro

Many nasopharyngeal carcinoma (NPC) biopsy specimens contain Epstein-Barr virus (EBV). However, the response of NPC cells to EBV infection in vitro and in vivo is not well characterized. In this experiment we infected NPC cells with EBV particles through endocytosis of a complex of EBV immunoglobulin A (IgA) secretory component (SC) protein to observe the response of host cells to the foreign viral infection in vitro. We found that EBV particles were endocytosed and stabilized in NPC nuclei 24 hours after infection; the EBV genomes were then gradually decreased after serial passages within 3 to 4 weeks by the following pathway: the EBV genomes first moved toward the nuclear envelope from the center of the nucleus; after crossing the nuclear envelope, they moved into the cytoplasm and toward the plasma membrane and were discharged by exocytosis. At the 10th day of EBV infection, EBV-latent membrane protein-1 and Epstein-Barr nuclear antigen (EBNA)-1 protein expressions could be detected, but not EBV-viral capsid antigen. Observation of EBNA-1 protein and host growth factor and cytokine gene expressions in the weeks after incubation revealed that the EBNA-1 protein expression was decreased proportionally with decrease of EBV genome. The mRNA expression of epithelial growth factor receptor, transforming growth factor (TGF)-alpha, interleukin (IL)-1beta, IL-6, and granulocyte-macrophage colony-stimulating factor increased within 1 to 2 weeks after infection, and gradually recovered to the original level at 3 to 4 weeks, whereas the mRNAs of TGFbeta1, TGFbeta receptor type I (TGFbetaRI), TGFbetaR type II, IL-8, and tumor necrosis factor-alpha remained unchanged. It is concluded that in vitro EBV infection in NPC cells results in increase of certain growth factor and cytokine gene expressions in host cells. The change in gene expression returns to the original level approximately 3 to 4 weeks after infection because of exocytosis of EBV DNA by the infected cells through an unidentified mechanism.     

Epstein-Barr virus infection in the pathogenesis of nasopharyngeal carcinoma.

The association of nasopharyngeal carcinoma (NPC) with the Epstein-Barr virus (EBV) was firmly established as early as 1973. Nevertheless, the role for the virus in the pathogenesis of NPC is still controversial. In this article, the evidence implicating EBV in the development of NPC is reviewed, focusing on the cellular site of EBV persistence, the association of the virus with different NPC histotypes, the tumour cell phenotype in the context of viral latent gene expression, and the possible role of the lymphoid stroma.     

Transitional cell papilloma of the penis associated with human papilloma virus infection. Report of two cases

Condylomas are one of the most common human papilloma virus (HPV)-related benign lesions of the male genitourinary tract. Although rarely, HPV has also been detected along the urinary tract, using molecular techniques, in transitional cell neoplasms without microscopic signs of koilocytic atypia. When affecting the urethra, condylomas are usually limited to its third distal portion. However, transitional cell neoplasms of the urethra are exceptional and in most of the cases remain limited to its proximal portion. To the best of our knowledge, 12 cases of transitional cell carcinomas and only one case of typical transitional cell papilloma have been described in the anterior urethra. We report two exceptional cases of typical transitional cell papilloma of the glans of the penis near the fossa navicularis which showed microscopic signs of HPV infection.     

Lack of Epstein-Barr virus infection in cervical carcinomas.

CONTEXT: The Epstein-Barr virus (EBV) is a ubiquitous microorganism strongly associated with lymphoproliferative disorders and a large number of human neoplasms, mainly undifferentiated nasopharyngeal carcinoma and Burkitt lymphoma. The viral DNA has been detected in other tumors, such as carcinomas from tonsil, salivary glands, and thymus, and malignancies of the female genital tract. Some authors have proposed that EBV could play a role in the carcinogenesis of cervical tumors; however, other studies do not support this hypothesis. OBJECTIVE: To assess whether EBV is associated with female genital tract neoplasms. DESIGN: Sixty-five biopsy specimens (5 in situ carcinomas, 24 invasive squamous cell carcinomas, 6 lymphoepithelioma-like carcinomas, and 30 endocervical adenocarcinomas) were used to perform EBV detection through RNA in situ hybridization. RESULTS: None of the cervical carcinoma cases studied was positive for EBV infection. CONCLUSIONS: The results suggest that it is still premature to incriminate EBV in the carcinogenesis of cervical carcinoma.     

The histology of acute autochthonous hepatitis E virus infection

AIM: To document the histological appearances of liver biopsies in autochthonous hepatitis E virus (HEV) infection. METHODS AND RESULTS: Four patients were serologically positive for HEV; three had no traditional risk factors, the fourth had recently returned from China. All four consumed meat products. Liver histology of the three autochthonous (locally acquired) cases showed portal tracts expanded by a severe mixed polymorph and lymphocytic inflammatory infiltrate, with a geographical distribution of polymorphs at the interface and lymphocytes centrally. Moderate to severe interface hepatitis and cholangiolitis were present. There was a striking acinar mixed inflammatory infiltrate made up of polymorphs, lymphocytes and macrophages; frequent apoptotic hepatocytes, focal necrosis, cholestatic rosettes and zone 3 canalicular and cytoplasmic bilirubinostasis were noted. Significant steatosis, megamitochondria and Mallory bodies were not present. There was no evidence of iron, copper or alpha(1)-antitrypsin accumulation. By contrast, the histology of the imported case of HEV infection showed less intense portal and acinar inflammation, no cholangiolitis and no geographical distribution of the portal inflammatory infiltrate. CONCLUSION: The histological appearances of autochthonous HEV infection are sufficiently distinctive to consider the diagnosis in an acute setting and possibly to differentiate it from the endemic form of the disease.     

喉癌发生中人乳头瘤病毒感染与Langerhans细胞、p53表达的关系

目的：探讨喉癌的发生机理。方法：应用免疫组化ＬＳＡＢ法对３０例喉鳞状细胞癌人乳头瘤病毒（ＨＰＶ）感染、Ｌａｎｇｅｒｈａｎｓ细胞（ＬＣ）及ｐ５３蛋白表达进行了研究。结果：２６．７％的病例可以检测到ＨＰＶ抗原成分。ＨＰＶ感染的癌旁粘膜内ＬＣ数量明显少于无感染者，且形态也发生改变。ｐ５３蛋白表达阳性率在ＨＰＶ感染组（３７．５％）明显低于ＨＰＶ检测阴性组（８３．３３％）。结论：提示ＨＰＶ、ＬＣ、ｐ５３在喉癌发生发展过程中起一定作用，且相互影响，ＨＰＶ感染引起ＬＣ数量减少，局部免疫功能降低，ＨＰＶ感染还可能通过表达的肿瘤蛋白或其他机制使抑癌基因ｐ５３失活，进而导致肿瘤的发生。     

Epstein-Barr virus DNA in nasopharyngeal carcinomas from Chinese patients in Hong Kong.

AIMS: To investigate the presence of Epstein-Barr virus (EBV) in cases of nasopharyngeal carcinoma (NPC) in Chinese patients living in Hong Kong. METHODS: Nasopharyngeal biopsy specimens, formalin fixed and paraffin wax embedded, from 24 patients, eight with undifferentiated nasopharyngeal carcinoma, eight with well differentiated squamous carcinoma, and eight showing normal tissue histology, were analysed for the presence of Epstein-Barr virus (EBV) DNA by slot-blot hybridisation on extracted unamplified DNA, and also after amplification of EBV specific sequences by the polymerase chain reaction (PCR). RESULTS: DNA slot-blot analysis showed viral DNA in all the undifferentiated, five of the well differentiated tumours, and none of the normal biopsy specimens. PCR studies confirmed positivity in the eight undifferentiated tumours, but six of the well differentiated tumours and three of the normal biopsy specimens showed viral DNA by this method, illustrating its greater sensitivity. CONCLUSIONS: EBV genome is present in appreciable copy number in most cases of well differentiated NPC in Chinese patients in Hong Kong.     

A histochemical method for demonstrating papilloma virus infection in paraffin-embedded tissue

In order to study the location of cells infected with human papilloma virus in paraffin-embedded tissues, the authors developed the following stain. Tissue sections were digested overnight with 0.01% deoxyribonuclease and then stained using the Feulgen stain with a light green counterstain. Cellular DNA was degraded, but viral DNA was not. Thus infected cells retained magneta nuclei, while uninfected cells stained a homogenous green. The stain was positive in 5/5 plantar warts, 7/8 verruca vulgaris, 2/2 laryngeal papilloma, and 18/20 condylomata accuminata. As a comparison, the indirect immunoperoxidase method on the same tissues stained 5/5 plantar warts, 6/8 verruca vulgaris, 0/2 laryngeal warts, and 2/20 condylomata accuminata. The presence of virus was confirmed by electron microscopic examination on one of the sections. Molluscum contageosum infected tissue also stained positively, but tissues infected with cytomegalovirus and herpes simplex virus did not. The only nonviral positive staining occurred with smears of sperm. The reasons for these results are discussed.     

Predictors of human papilloma virus (HPV) infection in Italian women

HPV infection is a “necessary cause” of cervical cancer and it is sexually transmitted. Due to upcoming mass vaccination investigation on risk factors for infection is the basis to implement prophylactic strategy even in older women. The aim of the study was to evaluate predictors of high‐risk (HR) HPV infection in adult women. Between 2006 and 2008, 100 women aged >18 years, with no previous treatment for cervical lesions, were screened for HR HPV infection in Rome, Italy. Risk factors for HPV infection were investigated through a questionnaire including: ethnicity, religion, education, marital status, sexual behavior, gynecological and obstetrical history, smoking and alcohol intake. Multivariate analysis identified the “never married–separated/divorced” status (OR: 3.38; 95% CI: 1.14–10.12) as predictor of HPV infection, while having a higher age at the first sexual intercourse (FSI) shows a protective effect (OR: 0.84; 95% CI: 0.71–1.00). A trend for the association between the infection and having more than three lifetime partners was also observed (OR: 2.57; 95% CI: 0.86–7.71). No significant association was found for other demographic characteristics investigated. These findings provide a contribution in the knowledge of an adult population defining a “high‐risk” sexual behavioral profile and could be helpful to target prophylactic strategies in older woman. J. Med. Virol. 82:1921–1927, 2010. © 2010 Wiley‐Liss, Inc.     

Human immunodeficiency virus infection in Haiti

This article reviews human immunodeficiency virus (HIV) infection in Haiti. The evolution of the epidemic in Haiti, its spread from urban to rural areas, its varied clinical manifestations, and the attitudes of Haitian people toward HIV infection provide important lessons on understanding and managing this infection in a developing country. The heterosexual spread of HIV, particularly among the poor, is well-documented as is the role of other sexually transmitted diseases along with tuberculosis. Coinfection of HIV and tuberculosis have led researchers to study the effects of six-month supervised intermittent tuberculosis therapy both in controlling tuberculosis and slowing the progression of HIV. Various surveys and discussion groups about acquired immunodeficiency virus knowledge and beliefs demonstrate a large deficit in HIV education despite campaigns to educate the population. The great impact of HIV disease on morbidity and mortality in Haiti indicates that a great deal of work still needs to be accomplished and demonstrates the frustration in fighting the infection in countries with inadequate resources and infrastructure. Advances in HIV vaccine research seem to be the most promising option for developing countries such as Haiti.     

Identification of epitopes in Indian human papilloma virus 16 E6: a bioinformatics approach

HPV-16 is reported as the cause of cervical and other related carcinomas. The early expressed protein E6 in cancer cells is found to be the target for immune therapeutic methods. The sequence of HPV-16 E6 (Accession No: ABK32509) from NCBI databank has been taken for this study. Hydrophilicity, flexibility, accessibility, turns, exposed surface, polarity and antigenic propensity scales were used for the B cell epitope prediction. MHC Class I and Class II alleles for the accession were predicted by the MHCPred 2.0 Program. The epitope sequences were also found out. Computer-based prediction program results show, A0203 and DRB0101 lower IC50 than other alleles. The best peptide binding affinity was 21HLCTELQTT30 of A0203 allele. In DRB0101 allele the peptide found was 39YCKQQLLRR48. Different structural features of the protein have also been predicted including glycosylation, kinase C phosphorylation, casein kinase II phosphorylation and N-myristylation sites. These computational prediction programs show four glycosylation, five kinase C phosphorylation, two casein kinase II phosphorylation, zero N-myristylation sites and seven disulphide sites. Development and approval of new vaccines are the keys for control of cancer. Epitopes and other structural features of protein prediction could be the best source of information and can help in molecular and medical studies of viral infection and development of HPV associated cancer drugs.