CD8 T cell response to human papillomavirus 16 E7 is able to predict survival outcome in oropharyngeal cancer.

Introduction: Immunological response to human papillomavirus (HPV) in the development and progression of HPV16+ oropharyngeal squamous cell carcinoma (OPSCC) (accounting for the majority of viral associated cases) is largely unknown and may provide important insights for new therapeutic strategies.

Methods: In this prospective clinical trial (UKCRN11945), we examined cell-mediated immune responses to HPV16 E2, E6 and E7 in peripheral blood using IFN-γ enzyme-linked immunosorbent spot assay. CD56, CD4, CD8 and regulatory T cell frequencies were also discerned by flow cytometry.

Molecular analyses of unselected head and neck cancer cases demonstrates that human papillomavirus transcriptional activity is positively associated with survival and prognosis.

Background: Human papillomavirus DNA detection in head and neck squamous cell carcinoma has been linked to improved patient prognosis. The main aims of the study was to test the hypotheses that HPV16 E6/E7 oncogene and p53 function within tumours were associated with the widely reported improved patient survival and prognosis in head and neck cancer.

Methods: HPV16 DNA, mRNA and p53 mRNA presence were analysed in a prospective study of 42 unselected HNSCC patients; correlating the data with patient age, tumour staging/grade, treatment response, disease recurrence and survival.

Treatment of warts and molluscum: what does the evidence show?

Purpose Of Review: Warts and molluscum contagiosum are very common viral skin infections, usually presenting in childhood. Despite the large number of people affected by them, high-quality trials of treatment are few and treatment is often chosen on the basis of cost, convenience and tradition.

Recent Findings: Over recent years, two further trials of the most commonly used treatments for warts, salicylic acid and cryotherapy, have been performed and for molluscum contagiosum, there is growing evidence for the use of irritants.

Deregulation of SYCP2 predicts early stage human papillomavirus-positive oropharyngeal carcinoma: A prospective whole transcriptome analysis.

This study was designed to identify significant differences in gene expression profiles of human papillomavirus (HPV)-positive and HPV-negative oropharyngeal squamous cell carcinomas (OPSCC) and to better understand the functional and biological effects of HPV infection in the premalignant pathway. Twenty-four consecutive patients with locally advanced primary OPSCC were included in a prospective clinical trial. Fresh tissue samples (tumor vs.

De-escalation treatment protocols for human papillomavirus-associated oropharyngeal squamous cell carcinoma: a systematic review and meta-analysis of current clinical trials.

Iatrogenic complications associated with current treatment protocols for oropharyngeal squamous cell carcinoma are noted to cause high rates of acute and chronic morbidity. The aims of this study are to provide an overview of the current de-escalation trials for human papillomavirus positive (HPV+) oropharyngeal carcinoma and to evaluate the evidence supporting improved response to treatment of patients within this viral cohort. This study reviewed all completed or in progress randomised controlled trials (RCTs) assessing clinical interventions for human papillomavirus-associated locally advanced oropharyngeal squamous cell carcinoma.

Host responses to infection with human papillomavirus.

Human papillomavirus (HPV) infections of cutaneous and genital mucosae are very common but the majority of individuals clear the infection without overt clinical disease. Those who develop lesions, also in most cases, mount an effective cell-mediated immune response and the lesions regress. The increased prevalence of HPV infections in individuals with a range of immunodeficiencies, including immunosuppression as a consequence of HIV infection, demonstrates the central importance of the CD4 T cell population in the control of established HPV infections.

De-escalation treatment protocols for human papillomavirus-associated oropharyngeal squamous cell carcinoma.

Background: Human papillomavirus-associated oropharyngeal squamous cell carcinomas are a distinct subgroup of tumours that may have a better prognosis than traditional tobacco/alcohol-related disease. Iatrogenic complications, associated with conventional practice, are estimated to cause mortality of approximately 2% and high morbidity. As a result, clinicians are actively investigating the de-escalation of treatment protocols for disease with a proven viral aetiology.

HIF isoforms in the skin differentially regulate systemic arterial pressure.

Vascular flow through tissues is regulated via a number of homeostatic mechanisms. Localized control of tissue blood flow, or autoregulation, is a key factor in regulating tissue perfusion and oxygenation. We show here that the net balance between two hypoxia-inducible factor (HIF) transcription factor isoforms, HIF-1α and HIF-2α, is an essential mechanism regulating both local and systemic blood flow in the skin of mice.

Detection of specific HPV subtypes responsible for the pathogenesis of condylomata acuminata.

Background: The low-risk human papillomavirus types 6 and 11 are responsible for approximately 90% of anogenital wart cases, with approximately 190,000 new and recurrent cases reported in the UK in 2010. The UK has recently selected the quadrivalent HPV vaccine, which conveys protection against both HPV6 and HPV 11, as part of its immunisation programme for 2012 and it is expected that this will reduce disease burden in the UK. The aims of the study were to evaluate current strategies used for the monitoring of HPV infection in genital warts and to assess the suitability of laser-capture microdissection (LCM) as a technique to improve the understanding of the natural history of HPV types associated with genital wart lesions.

HPV infection, anal intra-epithelial neoplasia (AIN) and anal cancer: current issues.

Background: Human papillomavirus (HPV) is well known as the major etiological agent for ano-genital cancer. In contrast to cervical cancer, anal cancer is uncommon, but is increasing steadily in the community over the last few decades. However, it has undergone an exponential rise in the men who have sex with men (MSM) and HIV + groups.

Campylobacter gastroenteritis associated with Sweet's syndrome.

Sweet's syndrome or acute febrile neutrophilic dermatosis has been associated with underlying infection, malignancy, inflammatory disease and certain medications. The infection agents associated with this include Streptococcus species, Yersinia species, Chlamydia species, Salmonella species and Helicobacter pylori. We report a case of Sweet's syndrome in a 73-year-old woman following a 2 week course of severe gastroenteritis caused by Campylobacter species.

Cutaneous scarring: Pathophysiology, molecular mechanisms, and scar reduction therapeutics Part II. Strategies to reduce scar formation after dermatologic procedures.

The evidence base underpinning most traditional scar reduction approaches is limited, but some of the novel strategies are promising and accumulating. We review a number of commonly adopted strategies for scar reduction. The outlined novel agents are paradigmatic of the value of translational medical research and are likely to change the scenery in the much neglected but recently revived field of scar reduction therapeutics.

High prevalence of HPV in non-cervical sites of women with abnormal cervical cytology.

Background: Human papillomaviruses (HPV) are causally associated with ano-genital and a subset of head and neck cancers. Rising incidence of HPV+ anal cancers and head and neck cancers have now been demonstrated in the developed world over the last decade. The majority of published data on HPV prevalence at the anal and oro-pharyngeal sites are from studies of higher-risk populations.

Analyses of human papillomavirus genotypes and viral loads in anogenital warts.

Condylomata acuminata (genital warts) are the most common sexually transmitted viral diseases. These lesions are caused by infection with mucosal human papillomaviruses (HPVs). However, there is limited information on HPV strain distribution involved in the molecular pathogenesis of these lesions.

Sensitive HPV detection in oropharyngeal cancers.

Background: Human papillomaviruses (HPV) are the aetiological agents of certain benign and malignant tumours of skin and mucosae; the most important of which is cervical cancer. Also, the incidence of ano-genital warts, HPV-anal cancer and oropharyngeal cancers are rising. To help ascertain a useful PCR detection protocol for oropharyngeal cancers, we directly compared three commonly used primer sets in detection of HPV from different clinical samples.

A prospective study on the natural course of low-grade squamous intraepithelial lesions and the presence of HPV16 E2-, E6- and E7-specific T-cell responses.

This study investigates the clinical course of low grade squamous intraepithelial lesions (LSIL), HPV status and HPV16-specific immune response in a large prospective study of 125 women with LSIL followed cytologically, virologically and histologically. Women with low-grade abnormal smears were recruited and followed-up for one year. Colposcopy, cervical biopsy for histology and brushings for HPV typing was performed at recruitment, 6 months (no biopsy) and upon completion of the study at one year.

A highly enriched niche of precursor cells with neuronal and glial potential within the hair follicle dermal papilla of adult skin.

Skin-derived precursor cells (SKPs) are multipotent neural crest-related stem cells that grow as self-renewing spheres and are capable of generating neurons and myelinating glial cells. SKPs are of clinical interest because they are accessible and potentially autologous. However, although spheres can be readily isolated from embryonic and neonatal skin, SKP frequency falls away sharply in adulthood, and primary sphere generation from adult human skin is more problematic.

The use of HPV Linear Array Assay for multiple HPV typing on archival frozen tissue and DNA specimens.

Accurate HPV typing is important for natural history and epidemiology studies. With the introduction of prophylactic multivalent HPV vaccines, there is also the need to determine the dominant genotypes in different populations and the effect of a vaccination programme on infection profiles. The interplay between multiple infection, viral persistence and implementation of interventions is a complicated one and therefore requires a reliable and accurate HPV detection and typing method.

Human papillomavirus gene expression in cutaneous squamous cell carcinomas from immunosuppressed and immunocompetent individuals.

Epidermodysplasia verruciformis (EV)-type human papillomavirus (HPV) DNA have been detected by PCR in squamous cell carcinomas (SCC) from both organ transplant recipients (OTR) and immunocompetent individuals. Their role in skin cancer remains unclear, and previous studies have not addressed whether the viruses are transcriptionally active. We have used in situ hybridization to investigate the transcriptional activity and DNA localization of HPV.

Recurrent herpes simplex virus type 2 infection of the hand complicated by persistent lymphoedema.

A 33-year-old, immunocompetent woman had recurrent herpes simplex virus reactivation of the right hand presenting with a cellulitis-like picture. She continued to have monthly debilitating recrudescences for more than 3 years until an adequate dosage of prophylactic antiviral therapy was achieved. After 2 years of repeated episodes she had chronic dull pain and developed persistent acquired lymphoedema of the left hand and forearm, which is an extremely rare complication.

Human papillomaviruses and skin cancer.

Cutaneous epidermodysplasia verruciformis (EV)-associated human papillomaviruses (HPVs) are found frequently in skin cancers especially in immunosuppressed people. They are also detectable in the normal skin and hair follicles of a proportion of individuals who have no immune defect. The available evidence to link HPVs causally with skin carcinogenesis is not conclusive, but includes epidemiological, molecular and immunological studies.

Efficient generation of neural precursors from adult human skin: astrocytes promote neurogenesis from skin-derived stem cells.

Background: Neural stem cells are a potential source of cells for drug screening or cell-based treatments for neurodegenerative diseases. However, ethical and practical considerations limit the availability of neural stem cells derived from human embryonic tissue. An alternative source of human neural stem cells is needed; a source that is readily accessible, easily expanded, and reliably induced to a neural fate.