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Papillomavirus
Kinds of Papillomavirus Terms modified by Papillomavirus Selected AbstractsTrials update in walesCYTOPATHOLOGY, Issue 2007A. Fiander Three ongoing studies will be presented and discussed. Prevalence of Human Papillomavirus Infection in a South Wales Screening population Methods: A total of 10 000 consecutive, anonymous liquid based cytology screening samples were collected over a five month period in 2004. Age, cytology result and social deprivation score was provided for each specimen. The methodology was chosen to ensure inclusion of all women attending routine cervical screening, avoiding potential constraints associated with obtaining individual informed consent. The liquid based cytology samples were processed and reported by the receiving cytology laboratory and the residual specimens sent to the HPV Research Laboratory, Wales College of Medicine, where they were processed and stored at -80°C until analysis. High risk and low risk HPV Typing was undertaken using PCR , EIA (Jacobs et al 1997). Full high risk typing was performed on HPV positive specimens. Results: The study population had a mean age of 38 years with 92% negative, 5% borderline and 3% dyskaryotic cytology. The average social deprivation score was 17.4 (based upon the Welsh Index of multiple deprivation). The following results will be presented: HPV prevalence by age. HPV prevalence by cytology result. Type specific HPV prevalence in single and multiple infection. Conclusion: This study represents the largest type specific HPV Prevalence Study in the UK to date. As such it will form a useful base line against which to access performance of marketed HPV tests and evaluating the impact following implementation of HPV vaccination. [Funded by Welsh Office for Research and Development] CRISP , 1 Study (Cervical Randomized Intervention Study Protocol -1) Background: Indole-3-carbinol (I3C) and Diindolylmethane (DIM) are found in cruciferous vegetables and have been identified as compounds that could potentially prevent or halt carcinogenesis. I3C spontaneously forms DIM in vivo during acid digestion. I3C has been shown to prevent the development of cervical cancer in HPV 16 transgenic mice and both I3C and DIM have been shown to promote cell death in cervical cancer cell models. DIM is the major active bi-product of I3C and preliminary data indicate that DIM is active in cervical dysplasia and may be better tolerated than I3C. Aim: To investigate chemoprevention of high grade cervical neoplasia using Diindolylmethane (DIM) supplementation in women with low grade cytological abnormalities on cervical cytology. Objectives: To observe any reduction in the prevalence of histological proven high-grade cervical intraepithelial neoplasia (CIN) after 6 months of supplementation. ,,To observe any reduction in the prevalence of cytological abnormalities. ,,To observe any changes in the clinical appearance of the cervix. To assess acceptability and monitor any side effects of DIM supplementation. ,,To assess whether any benefit is seen in relation to Human Papillomavirus (HPV) status including HPV Type, Viral load and integration. Methods: This is a double blind randomized placebo-controlled trial involving 600,700 women with low grade cytological abnormalities on a cervical smear. Randomization is in the ratio of 2 : 1 in favour of active medication. Women with first mildly dyskaryotic smear or second borderline smear are eligible. They are asked to take two capsules daily for 6 months. At the end of 6 months they undergo repeat cervical cytology, HPV testing and colposcopy. Results: A progress report will be given for this ongoing study. [Funded: - Cancer Research UK] Type Specific HPV Infection in Welsh Cervical Cancers Background: Whilst there have been numerous studies of HPV infection associated with cervical cancer and on prevalence of Human Papillomavirus in diverse populations there have been no studies of these variables in the same population. Against a background of prophylactic HPV vaccination it is important to assess potential protection against cervical cancer within a given population. The most comprehensive analysis of HPV type specific cervical cancer is a meta-analysis published by the IARC in 2003. This however included only three UK based studies, totalling 118 cases, 75 of which were only investigated by HPV type PCR for four high risk types. None of this data was presented with associated population based prevalence data. Therefore, the research objectives for this study in combination with the first study above, are as follows: To determine the frequency of specific HPV types in cervical cancers in Wales. To compare the distribution of specific HPV types amongst cervical cancers with their prevalence in the general population. This will allow accurate delineation of the relationship between prevalence of specific HPV types in the general population and their association with clinically relevant disease. This information is a pre-requisite to assess the potential impact of prophylactic vaccination against HPV infection in Wales. Methods: Welsh Cervical Cancer specimens from 2000,2005 will be identified from pathology departments within Wales. The pathology of each tumour will be reviewed by a single Gynaecological Pathologist. The age of the patient and pathological features of the tumour will be noted. DNA will be extracted from the paraffin sections and HPV typed by PCR-EIA. Results: A progress report will be given for this ongoing study. [Funded by Welsh Office for Research and Development] [source] Human Papillomavirus and Overexpression of P16INK4a in Nonmelanoma Skin CancerDERMATOLOGIC SURGERY, Issue 3 2004Ingo Nindl PhD Background. P16INK4a overexpression has been identified as a specific biomarker in high-risk human papillomavirus (HPV),infected cervical (pre)cancer lesions. Objective. To evaluate the overexpression of this cyclin-dependent kinase inhibitor in skin tumors depending on HPV infections, we analyzed normal skin, benign skin disease, and skin cancer specimens. Methods. Biopsies of 23 patients with normal histology (3), psoriasis (2), verrucae vulgaris (2), actinic keratoses (5), squamous cell carcinoma (SCC) in situ (3), Bowen's carcinoma (1), and SCC (7) were analyzed. Specimens of 23 patients were immunostained using the monoclonal antibody E6H4 specific for p16INK4a. HPV status was assessed by a polymerase chain reaction (PCR) system to detect all currently known HPV types. MY (MY09/MY11 and MYN9/MYN10)-, CP (CP65/CP70 and CP66/CP69)-nested PCR, and three single PCR methods CN1, CN3, and CN4 were used in a first step, and HPV typing was performed by restriction fragment length polymorphism analysis. Only ,-globin,positive patients were included in this study. Results. HPV DNA was detected in all actinic keratoses, SCC in situ, Bowen's carcinoma, and SCC, in 50% (one of two) of verrucae vulgaris, in 66% (two of three) of normal skin, and in none of two psoriasis. P16INK4a expression was not detected in normal skin, psoriasis, and verrucae vulgares. Overexpression of p16INK4a was detected in a subset of dysplastic cells (10% to 80%) of all skin (pre)cancer lesions such as actinic keratoses, SCC in situ, Bowen's carcinoma, and SCC infected with HPV independent of sun exposure. Conclusion. P16INK4a appears to be overexpressed in a portion of dysplastic cells from actinic keratoses and SCC. Further studies to examine the association of HPV infection and the overexpression of p16INK4a are warranted. [source] Human Papillomavirus (HPV) Infection in Southern Africa: Prevalence, Immunity, and Vaccine ProspectsIUBMB LIFE, Issue 4-5 2002Anna-Lise Williamson Abstract Human papillomavirus (HPV) associated cancers are more prevalent in developing countries compared to developed countries. The major cancer caused by HPV is cervical cancer. The humoral immune response to HPV can be a marker of past infection but may also reflect persistent infection and cervical disease. IgA antibodies to HPV in oral fluid were also found to be markers of cervical disease. Cell mediated immunity is important in clearing HPV infection and for regression of the associated lesions: this means that women infected with HIV have a high prevalence of co-infection with HPV. Good cervical screening programmes can control HPV associated cervical neoplasia. However, in countries such as South Africa, where these programmes are inadequate, there is a need for an HPV vaccine. The development of HPV vaccines is reviewed. There is a call for an inexpensive vaccine that will be accessible to the women that do not have access to adequate screening programmes and are therefore at the greatest risk of cervical cancer. [source] Human Papillomavirus and Cervical Cancer Knowledge, Health Beliefs, and Preventative Practices in Older WomenJOURNAL OF OBSTETRIC, GYNECOLOGIC & NEONATAL NURSING, Issue 3 2010Kymberlee Montgomery ABSTRACT Objective: To explore knowledge of Human Papillomavirus (HPV) and cervical cancer, health beliefs, and preventative practices in women 40 to 70 years. Design: Cross-sectional descriptive. Setting: Three urban ambulatory Obstetrics and Gynecology offices connected with a teaching hospital's Department of Obstetrics and Gynecology in the Mid-Atlantic section of the United States. Participants: A convenience sample of 149 women age 40 to 70. Methods: To assess HPV and cervical cancer knowledge, health beliefs, and preventative practices a self-administered survey, the Awareness of HPV and Cervical Cancer Questionnaire was distributed to women as they waited for their well-woman gynecologic exam. Results: The mean knowledge score was 7.39 (SD=3.42) out of 15. One third of the questions about the relationship of HPV and risks for cervical cancer were answered incorrectly by more than 75% of these women. Although most appreciate the seriousness of cervical cancer, they believed themselves not particularly susceptible. Conclusion: There is a need for HPV and cervical cancer awareness and education for women older than age 40. Women's health care professionals are well positioned to act as a catalyst to improve HPV and cervical cancer knowledge, health beliefs, and preventative practice to ensure optimum health promotion for all women. [source] Comparison of human papillomavirus genotyping using commercial assays based on PCR and reverse hybridization methodsAPMIS, Issue 10 2009FATIMA GALAN-SANCHEZ Different tests for human papillomavirus (HPV) screening are commercially available, detecting high-risk oncogenic HPV types with a pool of genotype-specific probes. However, it is necessary to establish reliable methods for the identification of individual genotypes. The purpose of this study was to compare three different commercial methods for HPV genotyping: INNO-LiPA HPV Genotyping v2 (LiPA), Linear Arrays HPV Genotyping Test (LA) and Clinical Arrays Human Papillomavirus (CA). A total of 83 HPV DNA-positive samples by hybrid capture method were genotyped (82, 78 and 81 by LiPA, LA and CA, respectively). Comparison analysis was limited to the HPV genotypes common to the three assays. There were concordant results (absolute agreement between assays) in 31 samples (39.7%) and compatible results (correspondence for some but not all genotypes) were found in 44 samples (56.4%). Only three samples (3.8%) were considered as discordant (did not show any similarity between the tests). Analyzing kappa values we have a very good agreement (>0.8) for HPV16 and HPV31 and good agreement (0.6,0.8) for HPV types 6, 18, 53 and 66 when all methods are compared. We conclude that all genotyping methods tested are highly comparable and suitable for clinical and epidemiological studies. [source] Significance of high-risk human papillomavirus detection by polymerase chain reaction in primary cervical cancer screeningCYTOPATHOLOGY, Issue 2 2001Y. L. Oh Significance of high-risk human papillomavirus detection by polymerase chain reaction in primary cervical cancer screening The purposes of this study were to evaluate the incidence of high-risk human papillomavirus (HPV) infection by polymerase chain reaction (PCR) and to assess its diagnostic usefulness in primary cervical screening. PCR testing for HPV type 16, 18, 31 and 33 was performed on 1305 specimens obtained during routine cervical cancer screening. We analysed the concurrent cervical smears and biopsy, and correlated them with the HPV infection status. We also evaluated histologically-proven cases with ASCUS smears according to HPV infection. HPV DNA was identified in eight (0.7%) of 1144 cytologically normal patients; nine (10.5%) of 86 ASCUS; seven (25.0%) of 28 LSIL; 26 (78.8%) of 33 HSIL; and in all of three squamous cell carcinomas (SCC). HPV positivity was significantly associated with cytohistological diagnosis for HSIL of more. In addition, HPV-positive ASCUS cases were found to be associated with histological abnormality rather than HPV-negative. The results indicate that high-risk HPV testing by PCR could be a useful adjunct tool for Pap smear in primary cervical screening. The combination of Pap smear and high-risk HPV testing by PCR might reduce unnecessary colposcopy-guided biopsy of women with cytological diagnosis of ASCUS. [source] Cervical screening: how often should women be screened?CYTOPATHOLOGY, Issue 2 2000A. Herbert Introduction As a result of major improvements that have been made to cervical screening during the last 15 years, and implementation of call and recall to invite all women aged 20,64 for screening, the incidence of cervical carcinoma has fallen by 42% since 19901. Cervical cancer is now a rare disease, largely thanks to the widespread uptake of screening by the women at risk. Despite the manifest success of the NHS Cervical Screening Programme (NHSCSP), there is pressure on one hand to improve its sensitivity by the introduction of new technology, including human papillomavirus (HPV) testing2, and on the other hand to reduce the cost of the programme, which is more than £130m per year. The main method suggested to reduce costs is the restriction of routine screening to an interval of 5 years3,5. [source] Human Papillomavirus and Overexpression of P16INK4a in Nonmelanoma Skin CancerDERMATOLOGIC SURGERY, Issue 3 2004Ingo Nindl PhD Background. P16INK4a overexpression has been identified as a specific biomarker in high-risk human papillomavirus (HPV),infected cervical (pre)cancer lesions. Objective. To evaluate the overexpression of this cyclin-dependent kinase inhibitor in skin tumors depending on HPV infections, we analyzed normal skin, benign skin disease, and skin cancer specimens. Methods. Biopsies of 23 patients with normal histology (3), psoriasis (2), verrucae vulgaris (2), actinic keratoses (5), squamous cell carcinoma (SCC) in situ (3), Bowen's carcinoma (1), and SCC (7) were analyzed. Specimens of 23 patients were immunostained using the monoclonal antibody E6H4 specific for p16INK4a. HPV status was assessed by a polymerase chain reaction (PCR) system to detect all currently known HPV types. MY (MY09/MY11 and MYN9/MYN10)-, CP (CP65/CP70 and CP66/CP69)-nested PCR, and three single PCR methods CN1, CN3, and CN4 were used in a first step, and HPV typing was performed by restriction fragment length polymorphism analysis. Only ,-globin,positive patients were included in this study. Results. HPV DNA was detected in all actinic keratoses, SCC in situ, Bowen's carcinoma, and SCC, in 50% (one of two) of verrucae vulgaris, in 66% (two of three) of normal skin, and in none of two psoriasis. P16INK4a expression was not detected in normal skin, psoriasis, and verrucae vulgares. Overexpression of p16INK4a was detected in a subset of dysplastic cells (10% to 80%) of all skin (pre)cancer lesions such as actinic keratoses, SCC in situ, Bowen's carcinoma, and SCC infected with HPV independent of sun exposure. Conclusion. P16INK4a appears to be overexpressed in a portion of dysplastic cells from actinic keratoses and SCC. Further studies to examine the association of HPV infection and the overexpression of p16INK4a are warranted. [source] An overview of human papillomavirus infection for the dermatologist: disease, diagnosis, management, and preventionDERMATOLOGIC THERAPY, Issue 5 2010Michelle Forcier ABSTRACT Genital human papillomavirus (HPV) is a common, usually transient, dermatologic infection transmitted by genital contact that can cause a variety of anogenital diseases, including warts (condyloma), dysplasia (cervical, vaginal, vulvar, anal), and squamous cell carcinoma. A number of treatment modalities are available to treat anogenital warts, both patient- and provider-applied. Treatment is efficacious, but lesions can recur. Bivalent and quadrivalent vaccines are approved to prevent HPV infection. Both are indicated to prevent cervical cancer, while the quadrivalent vaccine is also approved to prevent vaginal/vulvar cancers as well as genital warts in males and females. Providers should clearly explain the natural history and potential sequelae of HPV disease, counsel patients on prevention strategies, and recommend vaccination as an effective method of prevention to their patients. [source] Inflammatory events as detected in cervical smears and squamous intraepithelial lesionsDIAGNOSTIC CYTOPATHOLOGY, Issue 2 2010Anne M. E. Roeters M.D. Abstract The Dutch cytological coding system, KOPAC, enables to code for eight inflammatory events, that is koilocytosis (related to human papillomavirus (HPV)), Trichomonas, dysbacteriosis [related to bacterial vaginosis (BV)], Candida, Gardnerella, Actinomyces, Chlamydia, and non-specific inflammation (leucocytosis). This study presents an analysis of 1,008,879 smears. Of each smear, the age of the woman and the reason for smear taking (screening or indication) was available. The cytoscores (per mille) for these codes were calculated. For the screening smears, the cytoscores were for koilocytosis (HPV) 2.6, for Trichomonas vaginalis 1.9, for dysbacteriosis 31.4, for Candida albicans 9.8, for Gardnerella vaginalis 0.7, for Actinomyces 6.9, for Chlamydia 0.8, and for non-specific inflammatory changes 66.4. For the calculation of the Odds Ratio (OR), normal smears were used as a reference. The cytoscores for Chlamydia and Gardnerella covaried with high grade SIL (HSIL), with an OR of 7 and 12, respectively. In addition, the OR for Trichomonas vaginalis, for dysbacteriosis, and for leucocytosis proved to be significantly high in the indication smears. This study provides an oversight of HSIL and the full range of cervical infections as detected by cytology, proving that this infectious byproduct of screening can be very valuable. Diagn. Cytopathol. 2010. © 2009 Wiley-Liss, Inc. [source] Are adjunctive markers useful in routine cervical cancer screening?DIAGNOSTIC CYTOPATHOLOGY, Issue 7 2008Application of p16INK4a, HPV-PCR on ThinPrep samples with histological follow-up Abstract The objectives of the study were to evaluate 1) the diagnostic sensitivity and specificity of p16INK4a as a marker for high-grade cervical lesions, 2) the results of a real-time polymerase chain reaction detecting high-risk human papillomavirus, and 3) the interobserver variability of the p16INK4a interpretation. A total of 232 ThinPrep samples were stained for p16INK4a, and HPV-DNA PCR was performed on 107 specimens with inclusion of both benign and abnormal cytology. Histological follow-up information was collected. The diagnostic sensitivity of ASC+ with CIN2+ in histology as endpoint was 96% for p16INK4a and 100% for HR-HPV DNA PCR, and the diagnostic specificity was 41% and 27%, respectively. If p16INK4a had been used for triage of the ASC samples, then 18 patients (42%) could have been spared unnecessary follow-up procedures compared to six patients (21%) with the HR-HPV DNA test. Diagn. Cytopathol. 2008;36:453,459. © 2008 Wiley-Liss, Inc. [source] Results of longterm hospital based cytological screening in asymptomatic womenDIAGNOSTIC CYTOPATHOLOGY, Issue 3 2006Jata S. Misra Ph.D., M.I.A.C. Abstract Routine cytological screening has been carried out in 27,062 asymptomatic women attending Gynaec and Family Planning O.P.D. of Queen Mary's Hospital, Lucknow, India (April 1971,December 2004). Incidence of squamous intraepithelial lesion (SIL) was found to be 5.9% in the series, while cervical malignancy was seen in 0.6% of cases. The study highlighted the immense utility of cytological screening in minimizing the incidence of carcinoma cervix in the segment of the urban population screened, as the incidence dropped down to 0.5% in the second half from 1.1% noticed in the first half of the screening period. The study also emphasized the utility of clinically downstaging the cervical cancer as 7,316 women showing clinical lesions of cervix were found to harbor SIL in 15.3% and carcinoma cervix in 1.3% of cases as against the incidence of 2.5% for SIL and 0.6% for frank cancer in women with normal cervix. The investigation into different risk factors involved in cervical carcinogenesis revealed that the incidence of SIL and cancer cervix showed a rise with increasing age and parity and prolonged sexual period. The incidences of both cervical cytopathologies were also higher in women of low socio-economic status while religion was found to have no bearing on the occurrence of the disease. Among the four sexually transmitted diseases (STDs) diagnosed in the cervical smears, Trichomonas vaginalis was found to be more prevalent (2.6%), while human papillomavirus (HPV) and Herpes simplex was seen in 0.4 and 0.2% of cases, respectively Herpes simplex was found to have strong affinity with both SIL and carcinoma cervix, while only SIL incidence was high with HPV infection. The study emphasizes need of proper education to women of low socio-economic class for creating awareness regarding hazards and risk factors of cervical cancer as well as management and cure of the disease. Diagn. Cytopathol. 2006;34: 184,187. © 2006 Wiley-Liss, Inc. [source] A cost-effectiveness analysis of four management strategies in the determination and follow-up of atypical squamous cells of undetermined significanceDIAGNOSTIC CYTOPATHOLOGY, Issue 2 2005Alice A. Hughes M.S.P.H. Abstract Atypical squamous cells of undetermined significance (ASC-US) are the most common abnormal cytological result on Papanicolaou (Pap) smear. We analyzed four management strategies in a hypothetical cohort of women divided by age group: (1) immediate colposcopy, (2) repeat cytology after an ASC-US Pap smear result, (3) conventional Pap with reflex human papillomavirus (HPV) testing, and (4) liquid-based cytology with reflex HPV testing. Parameter variables were collected from previously published data. Strategies that included reflex HPV testing had the lowest overall costs for all age groups combined. Repeat Pap smears had the highest number of true positive results throughout all stages but also had the uppermost number of missed cancers and highest costs. Immediate colposcopy had the second highest overall costs and detected fewer true positive results than liquid-based cytology. Younger women (aged 18,24 yr) consistently had higher total costs for all strategies investigated. Using the incremental cost-effectiveness (CE) ratio, the immediate colposcopy strategy was more costly and less effective than liquid-based cytology and, therefore, was dominated. The incremental CE ratio was lowest for liquid-based cytology compared with conventional cytology and liquid-based cytology with reflex HPV testing was the most cost-effective strategy. Diagn. Cytopathol. 2005;32:125,132. © 2005 Wiley-Liss, Inc. [source] Detection of human papillomavirus DNA in squamous cell carcinoma of the esophagus by auto-nested PCRDISEASES OF THE ESOPHAGUS, Issue 2 2006A. P. Souto Damin SUMMARY., The aim of the present study was to investigate the presence of human papillomavirus (HPV) in surgical specimens of esophageal squamous cell carcinoma. One hundred and sixty-five paraffin-embedded specimens of esophageal carcinoma were analyzed through high-sensitivity auto-nested polymerase chain reaction (PCR) using the consensus GP5+/GP6+ primer. Twenty-six specimens of esophageal mucosa without malignant disease were also studied as a control group. Two different specific primer sets targeting the E6 region of the HPVs 16 and 18 were used for typing. Direct DNA sequence analysis was conducted to confirm positive PCR results. HPV DNA was detected in 26 esophageal carcinomas (15.75%), but in none of the benign esophageal specimens (P < 0.05). Out of the 26 positive cases, 24 were HPV-16 and one was HPV-18. One tumor contained both HPV-16 and -18 DNA. Positive PCR results were confirmed by the amplified viral sequences. Our findings suggest that the presence of either HPV-16 or -18 might be related to development of the malignant phenotype in the esophagus. [source] Therapeutic human papillomavirus DNA vaccination strategies to control cervical cancerEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2007T.-C. Wu Abstract A persistent human papillomavirus (HPV) infection is considered causal and necessary for the continued growth of cervical cancer. Thus, vaccination against HPV represents a plausible approach to prevent and treat cervical cancer. A report in the current issue of the European Journal of Immunology describes a therapeutic HPV DNA vaccination strategy using the HPV-16 E7 antigen fused to the invariant chain to enhance the E7-specific CD8+ and CD4+ T cell immune responses, resulting in a potent anti-tumor effect against E7-expressing tumors. Continued exploration of HPV therapeutic DNA vaccines may lead to eventual clinical application. See accompanying article http://dx.doi.org/10.1002/eji.200636233 [source] E6* oncoprotein expression of human papillomavirus type-16 determines different ultraviolet sensitivity related to glutathione and glutathione peroxidase antioxidant defenceEXPERIMENTAL DERMATOLOGY, Issue 6 2005Stéphane Mouret Abstract:, Clinical observations of non-melanoma skin cancer in immunocompromised patients, such as organ transplant recipients, suggest co-operative effects of human papillomavirus (HPV) and ultraviolet (UV) radiation. The aim of the present study is to evaluate UV sensitivity and DNA damage formation according to antioxidant status in HPV16-infected keratinocytes. We used SKv cell lines, infected with HPV16 and well characterized for their proliferative and tumorigenic capacities. We showed that SKv cell lines presented various E6* (a truncated form of E6) RNA levels. We demonstrated that the higher oncoprotein RNA expression level was associated with a higher resistance to solar-simulated radiation, more specifically to UVB radiation and to hydrogen peroxide. Moreover, this high resistance was associated with a low oxidative DNA damage formation after UV radiation and was related to high glutathione content and glutathione peroxidase activities. Therefore, the results of our study suggest that E6* levels could modulate the glutathione/glutathione peroxidase pathway providing a mechanism to protect HPV-infected keratinocytes against an environmental oxidative stress, such as UV radiation. [source] Possible involvement of epidermodysplasia verruciformis human papillomaviruses in the immunopathogenesis of psoriasis: a proposed hypothesisEXPERIMENTAL DERMATOLOGY, Issue 6 2003Slawomir Majewski Abstract:, We have shown previously in psoriasis a very high prevalence of epidermodysplasia verruciformis-associated human papillomavirus 5 (EVHPV5) DNA and antibodies to human papillomavirus 5 (HPV5) virus-like particle (VLP)L1, and we suggested that this benign hyperproliferative disorder could be a reservoir for EVHPVs. Here we provide new data confirming the expression of EVHPVs in psoriasis and present our hypothesis on their possible involvement in the immunopathogenesis of the disorder. The new important finding was detection by a radioimmunoprecipitation assay of a very high prevalence of antibodies to E6/E7 HPV5 oncoproteins, known to enhance keratinocyte proliferation. More recently, EV genes were identified, EVER1 and EVER2, whose mutations are responsible for epidermodysplasia verruciformis. Epidermodysplasia verruciformis-associated human papillomaviruses are harmless to the general population as a result of genetic restriction, which in psoriasis appears to be partly alleviated, and this may allow the viral gene expression. We hypothesize that induction of keratinocyte proliferation in psoriasis by various stimuli initiates the EVHPV life cycle with expression of early (E6/E7) and late (L1) viral proteins. The early proteins may, in turn, enhance the keratinocyte proliferation, and the late proteins could serve as a target for specific B- and T-cell-mediated responses. Immune responses against the viral antigens in the epidermis may result in chemoattraction of leukocytes and Munro abscess formation, as well as in production of proinflammatory cytokines, leading to self perpetuation of the psoriatic process. The novel immunomodulatory therapies could also inhibit immune responses against EVHPV proteins, leading to decreased cytokine production, keratinocyte proliferation and EVHPV expression. Thus the beneficial effect of these therapies is not discordant with the proposed hypothesis of possible involvement of EVHPVs in the immunopathogenesis of psoriasis. [source] Amplification of the telomerase reverse transcriptase (hTERT) gene in cervical carcinomasGENES, CHROMOSOMES AND CANCER, Issue 3 2002Anju Zhang The expression of telomerase reverse transcriptase (hTERT), the catalytic component of the telomerase complex, is required for activation of telomerase during immortalization and transformation of human cells. However, the biochemical and genetic mechanisms governing hTERT expression remain to be elucidated. In the present study, we examined hTERT amplification as a potential genetic event contributing to telomerase activation in cervical carcinomas. An amplification of the hTERT gene was found in 1/4 cervical cancer cell lines and 21/88 primary tumor samples derived from the patients with cervical carcinomas. An increase in the hTERT copy number was significantly correlated with higher levels of hTERT protein expression. Moreover, the hTERT alterations with the enhanced hTERT expression were exclusively observed in those tumors with high-risk human papillomavirus infection. Taken together, the hTERT gene amplification, directly or indirectly targeted by human papillomavirus, may be one of the driving forces responsible for upregulation of hTERT expression and activation of telomerase in cervical cancers. © 2002 Wiley-Liss, Inc. [source] HPV-positive/p16-positive/EBV-negative nasopharyngeal carcinoma in white North Americans,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 5 2010Jessica H. Maxwell MD Abstract Background Human papillomavirus (HPV) has been detected in keratinizing nasopharyngeal carcinomas (NPCs); however, the relationship between HPV and Epstein,Barr virus (EBV) among whites with nonkeratinizing NPCs remains unclear. The HPV, p16, and EBV status was examined in current University of Michigan patients with NPC. Methods From 2003 to 2007, 89 patients, 84 with oropharyngeal cancer (OPC) and 5 with NPC, were enrolled in an organ-sparing trial. Biopsy tissues from all 89 patients were evaluated for HPV and p16 expression. A separate HPV analysis of the 84 OPC patients is in progress. Among the patients with NPC, tumor tissue was also analyzed for EBV-encoded RNA (EBER). Results Five of 89 patients (5.6%) had NPC, all with nonkeratinizing histology. The 4 white patients with NPC were HPV(+) (subtype-16, subtype-18 [2 patients], and subtype-59)/p16(+)/EBER(-). One Asian patient with NPC had an HPV(-)/p16(-)/EBER(+) NPC tumor that developed distant metastases. Conclusion We postulate that HPV may be the etiologic factor in some EBV-negative, nonkeratinizing NPCs among whites. © 2009 Wiley Periodicals, Inc. Head Neck, 2010 [source] Head and neck squamous cell cancer and the human papillomavirus: Summary of a National Cancer Institute State of the Science Meeting, November 9,10, 2008, Washington, D.C.,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 11 2009David J. Adelstein MD First page of article [source] Use of combined molecular biomarkers for prediction of clinical outcomes in locally advanced tonsillar cancers treated with chemoradiotherapy aloneHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 1 2009Yih-Lin Chung MD Abstract Background. Environmental exposures to tobacco, alcohol, human papillomavirus (HPV) and/or Epstein-Barr virus (EBV), all of which can perturb multiple cell cycle proteins or tumor suppressors, have been implicated in the pathogenesis of different subsets of head and neck cancers. The aim of this study was to investigate to which extent the virus infection by itself, and/or the altered cell cycle proteins, contributes to prognosis in locally advanced tonsillar squamous cell carcinomas (TSCCs) treated with concurrent chemoradiotherapy (CCRT) alone. Methods. Serial tumor tissue arrays from archival samples were tested for the presence of HPV genome integration or EBV episome by means of DNA sequencing, real-time polymerase chain reaction (PCR), and in situ hybridization. Alterations of cell cycle proteins (p53, pRb, and p21) were evaluated by immunohistochemical staining. The association of viral presence with altered cell cycle proteins was correlated to clinical outcomes. Results. Of the 46 patients with the same T2N2bM0 stage IVA among consecutive patients with TSCC, 23 (50%) had integrated HPV DNA and only 1 (2%) had EBV episome. The HPV types detected were almost all HPV-16. A reduced expression pattern of p53, pRb, and p21 was noted in HPV-positive tumors, and the incremental number of alterations in the 3 proteins was significantly associated with HPV-negative tumors. The presence or absence of HPV together with the number of altered expression of the 3 cell cycle markers resulted in further identification of 4 biologically and clinically distinct subgroups with different outcomes after CCRT. Conclusions. Use of combined biomarkers of oncogenic HPV and tumor suppressors of p53, pRb, and p21 in advanced TSCC provides prognostic molecular classification superior to the TNM stage system and identifies low-risk patients for organ preservation by CCRT alone and high-risk patients who might benefit from planned tonsillectomy and neck dissection before or after CCRT. © 2008 Wiley Periodicals, Inc. Head Neck, 2009 [source] Deletion of the PDZ motif of HPV16 E6 preventing immortalization and anchorage-independent growth in human tonsil epithelial cellsHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 2 2008William C. Spanos MD Abstract Background Human papillomavirus 16 (HPV16) has been associated with head and neck squamous cell carcinoma (HNSCC) in up to 60% of sampled specimens. Methods To understand better the viral genes required to transform human tonsil epithelial cells (HTEC), we isolated HTEC's and transduced them with retroviral vectors containing HPV16 E6 and E7. Results Immortalization and anchorage-independent growth of HTEC's only occurred with expression of E6 and E7 with resultant degradation of p53. However, cells expressing E6 lacking the PSD-95/disc-large/Zo-1 (PDZ) motif did not immortalize or grow anchorage independent. Telomerase activity and degradation of p53 were similar for wild-type and mutant E6. Conclusion The mechanism of oncogenic transformation by E6 in HTEC's is dependent on the PDZ binding motif. Identification of pathways affected by the interaction of E6 and PDZ domain containing proteins will further our understanding of how HPV causes HNSCC and will provide potential therapeutic targets. © 2007 Wiley Periodicals, Inc. Head Neck, 2008 [source] High frequency of HPV16-associated head and neck squamous cell carcinoma in the Puerto Rican populationHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2004Adriana Báez PhD Abstract Background. Recent evidence has accumulated suggesting that human papillomavirus (HPV) plays a role in the development of head and neck squamous cell carcinoma (HNSCC). HPV16 is the most common of the HPV subtypes associated with oral and laryngeal malignancies. This study estimated the prevalence of HPV16 DNA in Puerto Rican patients with HNSCC. Methods. DNA was extracted from frozen tissue of 118 HNSCCs. Genomic DNA was screened for the presence of HPV16 DNA with E6-specific and E7-specific primers. Results. HPV16 was detected in tumor tissue of 52 patients (44%) with HNSCC. The oropharynx had a slightly higher incidence of HPV16 DNA. Fifteen of 66 patients with HPV16-negative HNSCC later had recurrences. Positivity for HPV16 was independent of the tumor grade, tumor stage, nodal status, and tobacco or alcohol use. The 3-year survival rate was higher in HPV16-positive patients than in HPV16-negative patients (36% vs 21%). Conclusions. Our findings suggest that HPV16 may play a role in the etiology of a subgroup of HNSCC in Puerto Ricans. Overall survival times of the HPV16-positive patients were not significantly different from those of HPV16-negative patients. Increasing our understanding of the role of HPV16 in the etiology of HNSCC might facilitate the development of new treatment modalities for this subgroup of HNSCC. © 2004 Wiley Periodicals, Inc. Head Neck26: 778,784, 2004 [source] The expression of key cell cycle markers and presence of human papillomavirus in squamous cell carcinoma of the tonsilHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 1 2004Wei Li MMed Abstract Background. Chemical carcinogens induce squamous cell carcinoma (SCC) of the head and neck by targeting the p53 and the retinoblastoma (pRb) pathways. Human papillomavirus (HPV) might have an etiologic role in these cancers at particular sites. Few studies have compared cell cycle protein expression in HPV-positive and HPV-negative tumors in this region. Methods. Fifty tonsil SCCs were analyzed for HPV by PCR and for expression of cell cycle proteins (p53, pRb, p16INK4A, p21CIP1/WAF1, p27KIP1, and cyclinD1) by immunohistochemistry. Results. HPV was present in 42%; almost all were type 16. There were statistical associations between HPV positivity and reduced expression of pRb and cyclinD1, overexpression of p16, and younger patient age. Tumor with down-regulated p27 tended to have down-regulated pRb and p21. Conclusions. HPV-positive tonsil SCCs have distinct molecular pathways. Their association with younger patient age suggests that they are biologically distinct from HPV-negative tumors. © 2004 Wiley Periodicals, Inc. Head and Neck 26: 1,9, 2004 [source] Human papillomavirus infection and cyclin D1 gene amplification in laryngeal squamous cell carcinoma: Biologic function and clinical significance,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 6 2002Giovanni Almadori MD Abstract Background Human papillomavirus (HPV) infection is suspected to be a risk factor for head and neck, and in particular for laryngeal, carcinogenesis. Cyclin D1 gene (CCND1) overexpression and amplification have been shown to play a role as prognostic factors in many human cancers, among which are head and neck cancers. Methods A literature review of the role in head and neck cancers of HPV infection and CCND1 overexpression and amplification was undertaken. We have evaluated the extent of the current knowledge in this field under the light of recent acquisitions, in particular, about a correlation between HPV infection, a suspected risk factor, and CCND1 amplification, a frequent mutation (about 20% of laryngeal cancers) and a prognostic factor in laryngeal SCC. Results and Discussion The significant correlation between HPV infection and CCND1 amplification supports the hypothesis of the involvement of HPV infection in laryngeal carcinogenesis and suggests that HPV positive laryngeal cancers may constitute a different subset of tumors with a peculiar molecular pattern and thus with a different clinical behavior. HPV infection may be considered a synergistic risk factor with smoking and/or alcohol consumption to be investigated in heavy smokers and drinkers, thus contributing to the identification of patient at high-risk for the development of laryngeal cancer who should undergo strict follow-up and primary and secondary prevention. © 2002 Wiley Periodicals, Inc. Head Neck 24: 597,604, 2002 [source] HPV triage testing or repeat Pap smear for the management of atypical squamous cells (ASCUS) on Pap smear: is there evidence of process utility?HEALTH ECONOMICS, Issue 5 2008Kirsten Howard Abstract A two-stage standard gamble was used to evaluate women's preferences for alternative managements of atypical squamous cells of undermined significance (ASCUS) on Pap smear (repeat Pap smear compared with immediate HPV test), and to test for the evidence of process utility. Women's utilities for the health state scenarios were clustered towards the upper end of the 0,1 scale with considerable variability in women's preferences. There was evidence of process utility, with immediate human papillomavirus (HPV) testing strategies having lower valuations than repeat Pap smear, where the clinical outcome was the same. Mean (95% CI) utilities for HPV testing (negative test) followed by resolution were 0.9967 (0.9957,0.9978) compared with repeat Pap smear followed by resolution: 0.9972 (0.9964,0.9980). Mean (95% CI) utilities for immediate HPV testing (positive test), followed by colposcopy, biopsy and treatment were 0.9354 (0.8544,1.0) compared with repeat Pap smear followed by colposcopy, biopsy and treatment: 0.9656 (0.9081,1.0). Our results add to the existing evidence that the impact of healthcare interventions on well-being is not limited to the effect of the intervention on the health outcomes expected from the intervention; process of care can have quality of life implications for the individual. A modelled application of trial-based data will allow characterisation of the true population costs, benefits, risks and harms of alternative triage strategies and subsequent policy implications thereof. Copyright © 2007 John Wiley & Sons, Ltd. [source] p16 Immunoreactivity in unusual types of cervical adenocarcinoma does not reflect human papillomavirus infectionHISTOPATHOLOGY, Issue 3 2010Oisin Houghton Houghton O, Jamison J, Wilson R, Carson J & McCluggage W G (2010) Histopathology,57, 342,350 p16 Immunoreactivity in unusual types of cervical adenocarcinoma does not reflect human papillomavirus infection Aims:, The association between human papillomavirus (HPV) and cervical carcinoma is well known, with HPV being identifiable in almost all cervical squamous carcinomas and most adenocarcinomas. However, the prevalence of HPV in unusual morphological types of cervical adenocarcinoma has not been investigated extensively. The aim was to determine HPV status in a series of primary cervical adenocarcinomas, enriched for unusual morphological types. The relationship between HPV and p16 immunoreactivity in these neoplasms was also investigated, as it is generally assumed that in cervical neoplasms diffuse p16 expression is predictive of the presence of high-risk HPV. Methods and results:, Sixty-three cervical adenocarcinomas, comprising those of usual type (n = 43), minimal deviation type (n = 4), gastric type (n = 3), intestinal type (n = 3), mesonephric type (n = 3), clear cell type (n = 4), serous type (n = 2) and hepatoid type (n = 1) underwent linear array HPV genotyping and immunohistochemistry for p16. Overall, HPV was identified in 32 of 56 cases (57%) in which sufficient DNA was present for analysis. The most common HPV types were 16 and 18, with these being identified in 20 and 18 cases, respectively, either alone or in combination. Seventy-eight per cent of usual-type adenocarcinomas were HPV-positive, as was the single serous carcinoma in which there was sufficient DNA for analysis. In contrast, all minimal deviation adenocarcinomas and those of gastric, intestinal, mesonephric and clear cell types were HPV-negative, as was the single hepatoid carcinoma. All usual-type adenocarcinomas exhibited p16 immunoreactivity (diffuse staining in all but one case), as did 11 of 20 of those of unusual morphological type (five focal, six diffuse). Conclusions:, Most, but not all, cervical adenocarcinomas of usual type contain HPV, but those of unusual morphological type are almost always HPV-negative. This has implications for the efficacy of HPV vaccination in the prevention of cervical adenocarcinoma. A significant proportion of cervical adenocarcinomas are p16-positive in the absence of HPV, illustrating that in these neoplasms diffuse p16 immunoreactivity is not a reliable surrogate marker of the presence of high-risk HPV. [source] Biomarker-assisted diagnosis of ovarian, cervical and pulmonary small cell carcinomas: the role of TTF-1, WT-1 and HPV analysisHISTOPATHOLOGY, Issue 3 2007J W Carlson Aims:, Small cell carcinoma of the ovary, hypercalcaemic-type (SCCOH) is morphologically similar to small cell carcinomas from other sites. The aims of this study were to (i) determine if a biomarker panel would distinguish small cell carcinomas of the ovary, cervix (SCCCx) and lung (SCCLu) and (ii) potentially determine the histogenesis of SCCOH. Methods and results:, Nine ovarian small cell carcinomas (seven hypercalcaemic type; two pulmonary type), eight SCCCx and 22 SCCLu were immunostained for thyroid transcription factor (TTF)-1, WT-1, p16, cKIT and OCT3/4; a subset of cases were tested for human papillomavirus (HPV). WT-1 was diffusely positive in 6/7 SSCOH versus two of 33 other small cell carcinomas (P , 0.001). TTF-1 was diffusely positive in 20/22 SCCLu and 1/8 SCCCx, and negative in all SCCOH. p16 and cKIT demonstrated variable patterns of immunoreactivity in all cases. HPV was identified in 5/6 SCCCx; SCCOH and SCCLu were negative for HPV. Conclusions:, Combined staining with WT-1 and TTF-1 will distinguish SCCOH from SCCLu and SCCCx with a sensitivity of 86% and specificity of 97%. HPV is specific for tumours of cervical origin, but p16 immunohistochemistry is not useful for this purpose. The presence of diffuse WT-1 supports a Müllerian origin for SCCOH, whereas the absence of cKIT and OCT3/4 argues against a germ cell origin. [source] CK17 and p16 expression patterns distinguish (atypical) immature squamous metaplasia from high-grade cervical intraepithelial neoplasia (CIN III)HISTOPATHOLOGY, Issue 5 2007S Regauer Aims:, Atypical immature metaplasia (AIM) refers to a full-thickness intraepithelial basaloid lesion in the uterine cervix that features both metaplasia and atypia and is therefore difficult to distinguish from high-grade cervical intraepithelial neoplasia (CIN III). p16 is a marker for human papillomavirus (HPV)-induced dysplasia. Cytokeratin (CK) 17 is a marker for cervical reserve (stem) cells, which give rise to metaplasia. The aim was to determine whether AIM can be reclassified into metaplasia and CIN III based on p16 and CK17 immunohistochemistry. Material and results:, Seventy-five cervical biopsy specimens, curettings and cone excisions containing varying proportions of dysplasia and metaplasia and 20 cases regarded as AIM were analysed immunohistochemically with antibodies to CK17, p16 and p63. In immature metaplasia all proliferating cells were immunoreactive with antibodies to CK17 and p63, while p16 was negative. All dysplastic cells of CIN III demonstrated uniform immunoreactivity for p16 and p63, but were CK17,. Based on the reciprocal immunoreactivity of p16 and CK17, 17/20 cases of AIM were reclassified as metaplasia (n = 10) and CIN III (n = 7). Three cases of AIM stained for both CK17 and p16 and were classified as CIN III. Conclusion:, ,AIM' is a helpful histological descriptor but it should not be used as a final diagnosis. Immunohistochemistry for p16 and CK17 allows distinction between metaplasia and high-grade CIN. [source] Altered patterns of the interferon-inducible gene IFI16 expression in head and neck squamous cell carcinoma: immunohistochemical study including correlation with retinoblastoma protein, human papillomavirus infection and proliferation indexHISTOPATHOLOGY, Issue 6 2004B Azzimonti Aims:, To investigate whether the expression of interferon (IFN)-inducible gene IFI16 is inversely related to proliferative activity in vivo, we compared immunohistochemical reactivity of IFI16 in a series of head and neck squamous cell carcinomas (HNSCCs) with their proliferation index and the cell cycle regulator pRb. As human papillomavirus (HPV) infection is manifested by changes in the function or expression level of host genes such as IFN-inducible genes, we also investigated the presence of HPV DNA to determine whether head and neck cancers associated with HPV DNA can be distinguished from tumours that are presumably transformed by other mechanisms. Methods:, Thirty-six HNSCCs were evaluated for IFI16, pRb and Ki67 expression by immunohistochemistry. The presence of HPV was also detected by polymerase chain reaction. Nine tumours were located in the oropharynx (tonsillar area) and 27 in the larynx. Results:, HPV DNA was found in 14 of 25 (56%) laryngeal SCCs and in five of nine (56%) tonsillar SCC specimens examined; 17 out of the 19 HPV-DNA-positive cases showed high-grade IFI16 expression. Overall, proliferative activity was significantly related to tumour differentiation and histological grading. IFI16 protein expression was significantly inversely correlated with Ki67 (P = 0.039). Low-proliferating tumours positive for IFI16 staining showed a marked expression of pRb and a better prognosis than those whose tumours had low IFI16, pRb levels and a high proliferation index. Conclusions:, To our knowledge, this is the first expression analysis of the IFN-inducible IFI16 gene in HNSCC. Low-proliferating tumours positive for IFI16 staining showed a marked expression of pRb and a better prognosis than those whose tumours had low IFI16, pRb levels and a high proliferation index. [source] | |||||||||||||||||||||||||||||||||||||||||||