HPV Virus Medical Facts - Study

Clifford GM, Rana RK, Franceschi S, Smith JS, Gough G, Pimenta JM. IARC, 150 Cours Albert Thomas, F-69372 Lyon cedex 08, France. clifford@iarc.fr.

Low-grade squamous intraepithelial lesions (LSIL) associated with certain human papillomavirus (HPV) genotypes may preferentially progress to cervical cancer. HPV genotyping may thus have the potential to improve the effectiveness of screening programs and to reduce overtreatment. LSIL cases (n = 8,308) from 55 published studies were included in a meta-analysis. HPV genotype distribution was assessed by geographic region and in comparison with published data on cervical squamous cell carcinoma (SCC). HPV detection in LSIL was 80% in North America but less than 70% in other regions, most likely reflecting regional differences in LSIL diagnosis. Among 5,910 HPV-positive LSILs, HPV16 was the most common genotype (26.3%) followed by HPV31 (11.5%), HPV51 (10.6%), and HPV53 (10.2%). HPV-positive LSILs from Africa were 2-fold less likely to be infected with HPV16 than those in Europe, and HPV-positive LSILs from North America were more likely to be infected with HPV18 than those from Europe or South/Central America. Interpretation for rarer genotypes was hampered by variation in HPV testing methodology. SCC/LSIL prevalence ratios indicated that HPV16 was 2-fold and HPV18 was 1.5-fold more common in SCC than in HPV-positive LSIL, thus appearing more likely to progress than other high-risk genotypes (SCC/LSIL prevalence ratios between 0.05 and 0.85). HPV53 and HPV66 showed SCC/LSIL ratios of 0.02 and 0.01, respectively. HPV genotype distribution in LSIL differs from that in cervical cancer, highlighting the importance of HPV genotype in the risk of progression from LSIL to malignancy. Some regional differences in the relative importance of HPV genotypes in LSIL were noted.

Gynecol Oncol. 2005 May 12; [Epub ahead of print]

Psychosocial factors and the course of cervical intra-epithelial neoplasia: A prospective study.

Tiersma ES, van der Lee ML, Garssen B, Peters AA, Visser AP, Fleuren GJ, van Leeuwen KM, le Cessie S, Goodkin K. Helen Dowling Institute, Center for Psycho-oncology, Utrecht, The Netherlands; Department of Obstetrics and Gynecology, Leiden University Medical Center, Leiden, The Netherlands.

OBJECTIVE.: To investigate the influence of psychosocial factors on the course of cervical intra-epithelial neoplasia (CIN). METHODS.: A group of 93 patients with CIN 1 or 2 was followed for 2.25 years by half-yearly colposcopy and cytology. Negatively-rated life events, social support, and coping style were studied in relation to distress during follow-up and in relation to time till progression and regression of CIN. Human papillomavirus (HPV) infection was controlled for as well as sick role bias caused by suspicion of having cervical cancer and distress due to the abnormal cervical smear. RESULTS.: During follow-up, progression was found in 20 patients (22%), stable disease in 22 patients (24%), and regression in 51 patients (55%). Negatively-rated life events and lack of social support predicted distress longitudinally. No association was found between progression or regression of CIN and negatively-rated life events, lack of social support, coping style, and distress. CONCLUSION.: We found no evidence that psychosocial factors influence the course of CIN.

J Virol. 2005 Jun;79(11):6838-47.

Human papillomavirus type 31b infection of human keratinocytes does not require heparan sulfate.

Patterson NA, Smith JL, Ozbun MA. Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131. mozbun@salud.unm.edu.

Oncogenic human papillomaviruses (HPVs) are difficult to study experimentally as they replicate at low levels in vivo. This has precluded the purification of high-risk HPV virions from in vivo lesions. Virus-like particles (VLPs) and pseudovirions from low- and high-risk HPV types can emulate various aspects of HPV virion attachment and infections. These studies suggest that HPV infection is mediated by alpha6-integrin and/or heparan-sulfonated receptors. However, whether VLPs and pseudovirions accurately reflect the infection process of HPV virions has not been verified. We generated infectious HPV31b virions from organotypic (raft) tissues and performed experimental infections in a variety of cells. Successful infection following viral attachment, internalization, and nuclear transport was assayed by detecting newly synthesized, spliced HPV transcripts using reverse transcription (RT)-PCR or RT-quantitative PCR. Most human epithelial cells were infected with HPV31b at a multiplicity of infection as low as 1 to 10 viral genome equivalents per cell. HPV31b infection was detected in other cell lines, including COS-7 monkey kidney cells, but higher viral multiplicities of infection were required. Heparin preparations of various molecular weights or heparinase I treatment of cells prevented HPV31b infection of COS-7 cells and C-33A human cervical cancer cells in reproducible and dose-dependent manners. However, these reagents were unable to block infection of human keratinocytes, including HaCaT and N/TERT-1 cells and low-passage human foreskin keratinocytes. These data suggest that HPV31b infection of human keratinocytes, the natural host cell for HPV infections in vivo, does not require a heparan-sulfonated receptor, whereas heparan sulfate is important for infection of some other cells.

Wiad Lek. 2004;57 Suppl 1:201-6.

Significance of the DNA-HPV research in cervical cancer prevention

HPV Virus Medical Facts - Article in Polish

The purpose of our research was to assess DNA-HPV frequention observation and evaluation of the diagnostic value mRNA E6 and E7 HPV16 and HPV18 profile concentration in prognostic risk of intraepithelial lesions and cervical cancer progression in women with cytological screening. Human papilloma virus (HPV) infection were detected in 13.8% normal samples, presence HPV16 and 18 in 7.5% samples were detected. HPV 16, 18 or HPV16 and 18 infection were detected in 85% HSIL (high-grade squamous intraepithelial lesion) samples. HPV16 or HPV18 infection in 100% cancer samples were detected. In samples from control group expression of E6 and E7 genes were not detected. In LSIL (low-grade squamous intraepithelial lesion) group HPV16 E7 gene in 2.6% samples, in HSIL group E7 gene in 9.5% samples were detected. In all cancer samples E7 or E6 HPV16 and/or HPV18 were detected.

Anticancer Res. 2005 Mar-Apr;25(2A):765-77.

Activity and therapeutic potential of ORI-1001 antisense oligonucleotide on human papillomavirus replication utilizing a model of dysplastic human epithelium.

Alam S, Bromberg-White J, McLaughlin-Drubin M, Sen E, Bodily JM, Meyers C. Department of Microbiology and Immunology, The Pennsylvania State University, College of Medicine, Hershey, PA 17033, USA.

Human Papillomaviruses (HPVs) are small double-stranded DNA viruses that infect the cutaneous or mucosal epithelium. The high-risk genital HPVs are associated with squamous intraepithelial lesions of the anogenital region that can progress to cancer. Cervical cancer is the third leading cause of cancer death in women worldwide, yet there are no specific therapeutic treatments for HPV-associated malignancies. Development of specific antisense oligonucleotides as antiviral agents is an alternative therapeutic strategy. We utilized the organotypic raft culture system which recapitulates the entire HPV life cycle, including the production of infectious virions. We studied the effect of the ORI-1001 antisense phosphorothioate oligonucleotide designed against the E1 mRNA translation start site of low-risk HPV6 and HPV11, and tested it against high-risk HPV31b and HPV16 vegetative replication and oncogene promoter activity. ORI-1001 significantly inhibited HPV31b genome amplification. In contrast, HPV16 genome amplification was unaffected. In addition, ORI-1001 significantly downregulated transcriptional activity from a HPV31b p99 early promoter luciferase reporter construct, and inhibited E1 and E6E7 transcript expression from the wild-type genome. Our results support the idea that the antisense activity of OR-1001 can target HPV31b functional activities in the differentiation dependent life cycle of this virus. Our results predict that binding stability between antisense oligonucleotides with partial homology to HPV genes may mediate targeting of multiple HPV types. Our studies also highlight the utility of the raft culture system in defining the parameters for testing antisense oligonucleotides against HPV.

HPV Virus Medical Facts - HPV Study Links

Cervical Cancer Prevention: Key Issues - This section provides brief summaries of some of the major research areas related to cervical cancer control in low-resource settings.

The Body: Human Papillomavirus - A lot of useful links on treatment and prevention of HPV are offered.