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Human organ transplantation: part 1. draft guiding principles on human organ transplantation: part 2. commercial transactions in human organs and tissues for therapeutic purposes: a review of international and national leglislation, codes and other measures: report by the Director-General
Executive Board, 87 ( 1990 )
Human organ transplantation: report by the Director-General
Executive Board, 79 ( 1986 )
Human organ transplantation: report by the Director-General
World Health Assembly, 44 ( 1991 )
Human papillomavirus (HPV) infection in squamous cell carcinomas arising from the oropharynx: detection of HPV DNA and p16 immunohistochemistry as diagnostic and prognostic indicators--a pilot study
Delogu, Giovanni; Paludetti, Gaetano; Petrone, Gianluigi; Almadori, Giovanni; Valentini, Vincenzo; Dinapoli, Nicola; Zannoni, Gian Franco; Santangelo, Rosaria; Galli, Jacopo; Sanguinetti, Maurizio; Autorino, Rosa; Vellone, Valerio Gaetano; Sali, Michela; Bussu, Francesco; Tommasino, Massimo; Rindi, Guido; Gallus, Roberto; Miccichè, Francesco; Graziani, Cristina ( 2014-07-08 )
PURPOSE: Human papillomavirus (HPV) 16 infection is associated with oropharyngeal carcinogenesis and is likely the cause of the reported increase in disease incidence. We evaluated the prevalence of HPV infection and the reliability of different diagnostic tools using primary tumor samples from a cohort of 50 patients. METHODS AND MATERIALS: Formalin-fixed paraffin-embedded (FFPE) tumor samples were collected from all 50 consecutive primary oropharyngeal SCC patients who were enrolled in the study; fresh tumor samples were available in 22 cases. NucliSENS EasyQ HPVv1 was used for RNA, and Digene Hybrid Capture-2(HC2) was used for DNA detection. p16 Expression was evaluated by immunohistochemistry in FPPE specimens. RESULTS: Based on the DNA detection assay on FFPE samples, the frequency of high-risk HPV infection was 32%. The agreement rate between HPV RNA and HPV DNA detection in fresh samples was 100%. The agreement rate between p16 immunohistochemistry (IHC) and the detection of HPV DNA in the FFPE samples was fair but not excellent (κ = 0.618). HPV DNA detection was highly significant, as measured by disease-specific survival and determined using a Wilcoxon test (P=.001). p16 IHC also exhibited a prognostic value but with a lower statistical significance (P=.0475). The detection of HPV DNA, but not p16 IHC, was also significantly correlated with locoregional control (P=.0461). CONCLUSION: Diagnostic methods based on the detection of HPV nucleic acids appear to be more reliable and objective because they do not require reading by a trained histopathologist. Furthermore, the detection of HPV DNA exhibits an improved correlation with survival, and therefore appears definitely more reliable than p16 IHC for routine use in clinical practice.
Human papillomavirus 16 E6 variants differ in their dysregulation of human keratinocyte differentiation and apoptosis
Zehbe, Ingeborg; Shai, Anny; Richard, Christina; Lichtig, Hava; Tommasino, Massimo; Lambert, Paul F; DeCarlo, Correne A; Sherman, Levana ( 2008-11-04 )
L83V-related variants of human papillomavirus (HPV) 16 E6, exemplified by the Asian-American variant Q14H/H78Y/L83V, were shown to be more prevalent than E6 prototype in progressing lesions and cervical cancer. We evaluated functions relevant to carcinogenesis for the E6 variants L83V, R10/L83V and Q14H/H78Y/L83V as well as the prototype in a model of human normal immortalized keratinocytes (NIKS). All E6 expressing NIKS equally abrogated growth arrest and DNA damage responses. Organotypic cultures derived from these keratinocytes demonstrated hyperplasia and aberrantly expressed keratin 5 in the suprabasal compartment. In contrast, differentiation and induction of apoptosis varied. The E6 variant rafts expressed keratin 10 in nearly all suprabasal cells while the prototype raft showed keratin 10 staining in a subset of suprabasal cells only. In addition, E6 variant NIKS expressing R10G/L83V and Q14H/H78Y/L83V were more prone to undergo cell-detachment-induced apoptosis (anoikis) than NIKS expressing E6 prototype. The combined differentiation and apoptosis pattern of high-risk E6 variants, especially of Q14H/H78Y/L83V, may reflect a phenotype beneficial to carcinogenesis and viral life cycle.
Human papillomavirus and HPV vaccines: a review
Claeys, P; Markowitz, L; Edmunds, W J; Castellsague, X; Garnett, G; Harper, D M; de Sanjose, S; Cutts, F T; Goldie, S; Goldenthal, K L; Franceschi, S ( 2007-09-01 )
Cervical cancer, the most common cancer affecting women in developing countries, is caused by persistent infection with "high-risk" genotypes of human papillomaviruses (HPV). The most common oncogenic HPV genotypes are 16 and 18, causing approximately 70% of all cervical cancers. Types 6 and 11 do not contribute to the incidence of high-grade dysplasias (precancerous lesions) or cervical cancer, but do cause laryngeal papillomas and most genital warts. HPV is highly transmissible, with peak incidence soon after the onset of sexual activity. A quadrivalent (types 6, 11, 16 and 18) HPV vaccine has recently been licensed in several countries following the determination that it has an acceptable benefit/risk profile. In large phase III trials, the vaccine prevented 100% of moderate and severe precancerous cervical lesions associated with types 16 or 18 among women with no previous infection with these types. A bivalent (types 16 and 18) vaccine has also undergone extensive evaluation and been licensed in at least one country. Both vaccines are prepared from non-infectious, DNA-free virus-like particles produced by recombinant technology and combined with an adjuvant. With three doses administered, they induce high levels of serum antibodies in virtually all vaccinated individuals. In women who have no evidence of past or current infection with the HPV genotypes in the vaccine, both vaccines show > 90% protection against persistent HPV infection for up to 5 years after vaccination, which is the longest reported follow-up so far. Vaccinating at an age before females are exposed to HPV would have the greatest impact. Since HPV vaccines do not eliminate the risk of cervical cancer, cervical screening will still be required to minimize cancer incidence. Tiered pricing for HPV vaccines, innovative financing mechanisms and multidisciplinary partnerships will be essential in order for the vaccines to reach populations in greatest need.
Human papillomavirus laboratory manual
World Health Organization. Dept. of Immunization, Vaccines and Biologicals ( 2010 )
Human papillomavirus prevalence to age 60 years among Australian women prevaccination
Garland, Suzanne M; Whinurs Study Group, On Behalf Of The; McIntyre, Peter B; Brotherton, Julia M L; Condon, John R; Malloy, Michael; Tabrizi, Sepehr N ( 2015-06-01 )
Background The prevalence of human papillomavirus (HPV) at the cervix varies with age, peaking following sexual debut and declining thereafter in most populations. In some populations, a second peak is observed. Here we describe the prevalence of HPV at the cervix among Australian women before the commencement of the HPV vaccination program.Women aged 15 to 60 years attending health services for cervical screening between 2005 and 2008 were invited to participate. Liquid based cervical specimens were tested for 37 types of HPV using linear array. The percentage and 95% confidence interval of women with any type of HPV, any of 13 high risk HPV types, and with vaccine-preventable HPV types (types 6, 11, 16 and 18) were estimated in 5-year age bands.Among 1929 women aged 15-60 years, HPV prevalence peaked at 64% at age 15-20 years, then declined gradually to 12% at age 41-45 years, whereafter it rose to 19% in women 51-55 years then returned to 14% in 56-60 year olds. Prevalence curves were similar for high-risk HPV types and vaccine-targeted HPV types 6, 11, 16 and 18 and when results were restricted to women with only normal cytology.The shape of the prevalence curve we observed is similar to those from other Western populations. Variation in prevalence curves is likely due to differences in sexual behaviour between populations and over time, reactivation of HPV during perimenopause, and possibly the presence of cervical screening programs. These data are the first such data from the Oceania region.
Human papillomavirus types detected in skin warts and cancer differ in their transforming properties but commonly counteract UVB induced protective responses in human keratinocytes
Serour, Francis; Heyman, Dariya; Tommasino, Massimo; Gonen, Pinhas; Yaniv, Abraham; Chaouat, Malka; Sherman, Levana; Jackman, Anna; Shapiro, Beny; Shterzer, Naama ( 2014-10-14 )
In the present study, E6E7 and E6 proteins of human papillomaviruses (HPVs) associated with skin warts and cancer were compared for their transforming and carcinogenic abilities in primary human keratinocytes (PHKs). We show that E6E7 of cancer associated beta HPV types, notably 49 and 24, were able to extend the life span and enhance the clonogenic efficiency of PHKs when maintained in serum free/low calcium medium. Activities of the beta HPV E6E7 were lower than those of HPV16 E6E7. In contrast, E6 proteins from HPV types detected in skin warts or cancer, notably 10, 49 and 38, attenuated UVB induced protective responses in PHKs including cell death, proliferation arrest and accumulation of the proapoptotic proteins, p53, bax or bak. Together, this investigation revealed functional differences and commonalities between HPVs associated with skin warts and cancer, and allowed the identification of specific properties of beta HPVs supporting their involvement in skin carcinogenesis.