- Meeting Report
- Open Access
An overview of viral oncology in Italy - report from the Pavia meeting on solid tumors
© Perfetti et al.; licensee BioMed Central Ltd. 2012
- Received: 5 July 2012
- Accepted: 30 August 2012
- Published: 5 September 2012
This is a report on some of the research activities currently ongoing in Italy as outlined at the “Viruses and solid tumors” meeting jointly organized by the Oncology Sections of IRCCS Policlinico “San Matteo” (Pavia) and IRCCS National Cancer Institute (Aviano), held in Pavia, Italy, on October 2011. Experts from the various disciplines involved in the study of the complex relationships between solid tumors and viruses met to discuss recent developments in the field and to report their personal contributions to the specified topics. Secondary end point was to establish a multidisciplinary work group specifically devoted to solid tumors and infectious agents, aimed to identify areas of common interest, promoting and establishing collaborative projects and programs, and to coordinate clinical and research activities. The group, which will be named IVOG (Italian Viral Oncology Group), will operate under the patronage of the various scientific societies of interest.
- Cervical Cancer
- Sustained Virological Response
- Malignant Mesothelioma
- Merkel Cell Carcinoma
- Sustained Virological Response Rate
The first introductory lecture dealt with the fundamental milestones of the long lasting and successful research on viruses and cancer, such as the discovery of transforming non-filterable agents that cause cancer, the identification of the first human tumor virus (EBV), the discoveries of proto-oncogenes (SRC) and tumor suppressor genes (p53, Rb), and the first vaccination achievements (HBV, HPV) (Umberto Veronesi, Istituto Europeo di Oncologia, Milan, Italy). Then it was the turn to address the intimate mechanisms of direct and indirect virus oncogenesis, illustrating the key steps and complex regulatory circuits that contribute to the cancer development (Giorgio Palù, University of Padova, Italy). At the end, Antonino Carbone (National Cancer Institute, Aviano, Italy) reviewed the molecular techniques for pathologic and virologic investigations, including DNA/RNA detection techniques and conventional immunohistochemistry for EBV, KSHV, MCPyV and HPV.
Epidemiology of virus-associated cancers was introduced by Diego Serraino (IRCCS Centro di Riferimento Oncologico, Aviano, Italy) who presented an interesting study on HLA-A and -B high-resolution profile in EBV-associated undifferentiated nasopharyngeal carcinoma (UNPC) in Italy, a non endemic area for this disorder ; it was shown that affected individuals present distinct HLA- genetic profile, with significant hyper- and under-representation of specific alleles, compared to bone marrow donors. As for other virus-driven tumors, the lack of an HLA background favoring an efficient immune control of EBV-infected cells may increase the risk to develop nasopharyngeal carcinoma, with data that are relevant for immunotherapy (EBV specific CTLs and vaccines) in these areas.
The estimated total number of cancer cases attributable to infection in the year 2002 was 1.9 million, or 17.8% of the global cancer burden . The attributed fraction at the specific sites varied from 100% of cervical cancers attributed to the papilloma viruses to a tiny proportion (0.4%) of liver cancers (worldwide) caused by liver flukes. Analysis of a number of cancer cases attributed to infection by age group indicated that in developing countries virus-associated cancers cluster in the 50–69 age group. Silvia Franceschi, the epidemiologist director of the Infection and Cancer Epidemiology Group at the WHO/OMS International Agency for Research on Cancer (IARC, Lyon, France), focused the attention on HPV as a good example of a carcinogenic infection with the typical features of an etiological association between infections and human cancers. Data from the IARC Prevalence Surveys, 1990–2011, indicated that the prevalence of cervical HPV DNA in Italy was about 9%. Franceschi presented a recent meta-analysis of HPV type-specific prevalence data published from 1990 to 2010, including a total of 243 studies and 30,848 invasive cervical cancers (ICC) . Results showed that the proportion of ICC associated with HPV-16 and HPV-18 was between 70 and 76% in all world regions except for Asia. The 12 most common HPV types identified, in order of decreasing prevalence, were HPV-16 (57%), 18 (16%), 58, 33, 45, 31, 52, 35, 59, 39, 51 and 56. The prevalence of other types, phylogenetically related to those above, ranged from <0.1% for HPV 85 to 0.6% for HPV-68. There was a significant increase in the prevalence of multiple infections (from 4.0%, year 1990, to 15.7%, year 2010) and of HPV-16 (from 51.8 to 60.0%). Smaller, but relevant increases were also seen for HPV-39, 53 and 58. According to recent data, the fraction of anus cancer attributable to HPV infection raised to 88%.
In recent studies the involvement of HPV infection in head and neck cancers was investigated. Data indicated that the fraction of oropharynx, tonsils and base of tongue cancers attributed to HPV was 50% in developed countries and 5% in developing countries (where smoke and alcohol were the major risk factors). The natural history of cervical HPV infection is well studied, whereas the extension of cervical findings to HPV carcinogenesis in the tonsil needs more investigations. Cervical HPV infection is mainly transmitted through sexual intercourse, and is very common and rising in all world population. On the other hand, information on the prevalence and the age at first acquisition of HPV infection to the oropharynx is limited in quantity and quality. HPV-16 was found in 50% of cervical carcinoma and in 90% of HPV-positive carcinomas of the oropharynx. The precancerous HPV-associated lesions that precede cervical carcinoma (CIN1-3) are well defined and widely employed in screening programs. In contrast, precancerous lesions in the oropharynx are poorly understood and not consistently classified. Contrary to cervical carcinoma, very strong risk factors, other than HPV, exist for oropharyngeal carcinoma (mainly smoke and alcohol). In conclusion, Franceschi presented the future objectives emerged from the FP-7 funded IARC Study of human Papillomavirus and precancerous Lesions In the Tonsil (SPLIT study): i) prevalence of HPV infection in cancer-free tonsils and age at acquisition; ii) detection of precancerous lesions in the tonsil using histological and cytological examinations; iii) differences between HPV-related precancerous lesions in the oropharynx and those caused by other risk factors (smoke, alcohol); iiii) fraction of oropharyngeal carcinomas truly attributable to HPV, in different countries.
Franco Buonaguro (National Cancer Institute, IRCCS Fondazione “G. Pascale”, Napoli, Italy) introduced the section summarizing features of HPV virus replication, transmission, and immune response. Then the speaker focused the attention on HPV vaccines. Target of preventive vaccines is neutralization of virus before infection of basal keratinocytes. Actual vaccines are based on recombinant L1 protein, a major capsid protein, which is characterized by self assembly to form virus-like particles in vitro. Quadrivalent HPV (type 6, 11, 16, 18, from MERCK) and bivalent HPV (type 16, 18, from GSK) L1 VLP vaccines are available, and their efficacy was demonstrated in phase III trials. Results from a phase II randomised placebo controlled trials of a quadrivalent HPV  and bivalent HPV L1 VLP vaccines  demonstrated efficacy in prevention of incident and persistent cervical infections with HPV-16 and HPV-18, and associated cytological abnormalities and lesions. Protection appears to last for 4–5 years. In a IARC Working Group meta-analysis  HPV-16, 18, 45, 31, 33, 35, 52, 58 were the most common HPV types found in invasive cervical cancer. The risk classification of the different HPV types is important for screening and vaccine development, and it’s an open debate, since the oncogenic potential of many virus types is yet to be defined. Another open issue that may have a great impact on the virus transmission to women is HPV vaccination of men, given the role of carrier. To test for the prevalence of HPV infection in immunocompromised patients in Italy, the presence of HPV infection was investigated in urine samples of 88 male patients with renal transplants . The results showed that 48.9% of the samples were positive for HPV sequences, with high prevalence of HPV-16 (53.5%). These results suggested that HPV-16 based preventive or therapeutic vaccine may be effective for prevention and treatment of HPV-related neoplasia in this group of immunocompromised patients.
As regards new HPV vaccines technologies, research is focused on the production of capsomers and in low-cost synthesis. Vaccine production in other systems, such as in plants will permit safer and cheaper synthesis of viral molecules for the developing world. The author is actively pursuing vaccine development in tobacco plants. Therapeutic vaccines are also under development, specifically based on several long peptides derived from proteins E6 and E7. While these strategies have proven to be successful in animal models of HPV neoplasia (mice and rabbits), ways to improve the T helper 1 response are being investigated, including the use of dendritic cells exposed to viral peptides ex vivo.
The role of antiviral therapy in HCC prevention was introduced by Raffaele Bruno (Fondazione IRCCS Policlinico “San Matteo”, Pavia, Italy) who presented a collaborative retrospective study of the Italian Association for the Study of the Liver (AISL)  on the impact of sustained virological response (SVR) on the long-term outcome of 848 patients with HCV-related cirrhosis treated with IFNα. The results showed that the patients with SVR had a lower risk of liver-related complications and a reduction in liver-related mortality. Another prospective study from Bruno et al.  conducted on 352 patients with compensated HCV-induced cirrhosis, confirmed that the achievement of SVR was associated with a reduction of decompensation rate and mortality. These studies also showed that patients with SVR had a lower risk of HCC development. A further study  investigated the impact of antiviral therapy in decompensated HCV-related cirrhotic patients. The results showed that the achievement of a SVR in these patients reduced disease progression and may be life-saving. However, SVR rates were significantly lower in patients with advanced fibrosis . SVR rate is also associated with viral genotype. SVR is higher in genotype 2 patients, and so these patients have an advantage in the treatment response .
Cell-based immunotherapy against virus-mediated cancers was discussed by Patrizia Comoli (Fondazione IRCCS Policlinico “San Matteo”, Pavia, Italy). The investigator illustrated the last 15 years experience on cell therapy for EBV-related PTLD in immunocompromised patients . Cell therapy was based on generation of EBV-specific CTLs that were used in their experience after preemptive rituximab failure. In high-risk cohorts, such as haplo-HSCT recipients, infusion of donor EBV-specific CTLs contributed to a significant improvement of outcome , and induced viral DNA clearance and remission of PTLD in all treated patients . More recently this cell therapy was applied to EBV-related solid tumors, such as nasopharyngeal carcinoma (NPC), in particular in the subset of patients that relapsed after chemo-radiotherapy treatment. Data from the first study conducted  showed that successful autologous cell therapy was typically observed in patients with high titers of LMP2-specific responses, with disease control in approximately 50% of patients. With the aim to potentiate in vivo T-cell expansion, lymphodepletion was employed before high-dose EBV-specific CTLs in eleven EBV-related NPC, but results were comparable . These preliminary data constituted the ground for an ongoing preclinical study, presented by Comoli, on the production and expansion of LMP2-specific CTL from NPC patients. The conventional procedure of cellular activation is modified by means of LMP2 peptide (15aa) mix. The cell lines obtained by this protocol were successfully used in the treatment of a pediatric patient with refractory NPC. Future studies will attempt to optimize the generation of LMP2-specific CTL in order to increase the rate of T-cells specific for the antigens present on NPC. An important future perspective will be to employ cell therapy in early phases of disease, within a wider protocol, as part of first line treatment or to prevent tumor recurrence in the adjuvant setting.
Contributions of the last section were focused on HIV-associated solid tumors. WHO estimates 33.3 million of adults and children infected with HIV in the world, about 820,000 in Europe. In the HAART era, HIV-infected patients survive to older ages, with prolonged exposure to cancer risk factors and, nowadays, non-AIDS Defining Cancers (NADC) represent a much larger fraction of the overall cancer burden. NADC are constituted mainly by Hodgkin’s lymphoma and some solid tumors (lung carcinoma, hepatocarcinoma, GE tumors, head and neck, and anal cancers, skin non melanoma cancers, in decreasing order of frequency) associated with alcohol and smoke exposure, immunedepression, and viral infection (HCV, HPV, HHV-8, MCPyV). Emanuela Vaccher (CRO National Cancer Institute, Aviano, Italy) analyzed data of a recent record-linkage study between the Italian AIDS registry and the Italian cancer registries [39, 40]. This study allowed to obtain the standardized incidence ratio (excess risk compared to a general population matched for age and sex, SIR) of cancer in 21,951 AIDS cases reported in Italy between 1986 and 2005, before and after the introduction of HAART. Results showed interesting changes in the cancer pattern after the introduction of HAART in 1996. SIR for Kaposi sarcoma (KS) and non-Hodgkin lymphoma greatly decreased in post-HAART era (although the risk for these cancers remains substantially higher for HIV patients), whereas SIR for invasive cervical cancer, an AIDS defining cancer, were substantially stable, at high levels, in the two periods analyzed. From analysis of the epidemiological data, it is clear that the risk for most NADC were already high in the pre-HAART, with no significant increase in the HAART period, except for HCC (SIR = 6.4) . By analysis of the overall Incidence Rate Ratio (IRR), no significant differences in NADCs emerged after the HAART introduction . Data showed that HCC and lung cancer were the only tumors with increased incidence in the last years in Italy (4.6 and 1.8 times, respectively). An interesting data to investigate further is the impact of aging in the risk of NADCs development of HIV-infected people. Age-specific incidence rates for NADCs in AIDS patients were higher than the corresponding curve in the general population below 45 years of age in pre-HAART and below 55 years of age in HAART era. The analyses of 595 HD cases and 550 solid tumors cases in the CRO-GICAT data base (06/2010) indicated that the major characteristics of HIV-infected patients with solid non-AIDS defining malignancies, compared to the general population were: middle-age groups, more advanced disease stages III-IV (49-93%), and poorer prognosis. National guidelines about HAART administration and diagnostic/clinical approach of HIV-1 patients, introduced some important concepts: NADC patients must be treated with chemotherapy and HAART independently by CD4 count and HIV-RNA; antineoplastic therapy has only support finality in patients without HIV therapeutic chance.
Attention was then focused on HCC and HIV. HCC is an increasing cause of mortality in HIV-infected patients in the HAART era; the risk of HCC is increased in HIV patients (SIR = 3-19). Furthermore, HIV is able to accelerate the evolution process of fibrosis/cirrhosis. In the Italian cohort, 1 year survival of 28% in HIV-positive patients versus a survival of 76.2% in HIV-negative patients has been reported. Antonello Malfitano (Fondazione IRCCS Policlinico “San Matteo”, Pavia, Italy), presented some contributions that explain the main features, clinical presentation and outcome of HCC in HIV-infected patients. The first study presented  was based on 41 HIV/HCC patients, that were identified from the GICAT case series in the period 1995–1998. Results showed that in HIV-infected patients liver disease was significantly more advanced at presentation, with higher prevalence of multifocal and infiltrating lesions. Only three variables were significantly more frequent in HIV-positive patients compared with uninfected patients: a higher rate of chronic hepatitis C, a lower prevalence of heavy alcohol intake and a higher frequency of infiltrating lesions and metastasis at first HCC diagnosis. Further aspects to be highlighted were the shorter interval between the estimated date of first HCV exposure and first diagnosis, and the younger age of HIV-positive patients (median age at first diagnosis, 42 years) compared with HIV-negative HCC patients. The process of hepatocarcinogenesis could be more rapid in HIV/HCV-coinfected patients, and an increasing number of cases should be expected in the next few years. A most recent multicenter observational retrospective comparison of 104 HIV/HCC patients and 484 uninfected HCC patients over 13-year period, 1997–2010, was reported . Results of this study confirmed a significantly shorter survival time in HIV-positive HCC patients, despite better Barcelona Clinic Liver Cancer (BCLC) stage at diagnosis and a similar therapeutic option rate.
Last contribution was focused on AIDS-Kaposi’s sarcoma (AIDS-KS). AIDS-KS is the most aggressive form of KS, and Kaposi’s sarcoma herpesvirus (KSHV, also named human herpesvirus 8, HHV-8) is the infectious agent associated with this neoplasia. AIDS-KS most frequently manifests in a multifocal mucocutaneous distribution involving the face, trunk, genitalia, and/or lower extremities. Visceral sites most commonly include the lung and gastrointestinal tract. KS predictive factors are immune system impairment, current CD4+ cell count, current viral load, and absence of combination antiretroviral therapy (cART) . KS risk increases as the CD4+ cell count fell, and is associated with high viral load. HAART is the mainstay of AIDS-KS treatment; other therapeutic approaches can be local (radiation, surgical), interferons, and chemotherapy. Renato Maserati (Fondazione IRCCS Policlinico “San Matteo”, Pavia, Italy), presented some studies [44, 45] focused on various aspects of HAART therapy, demonstrating that HAART therapy was successful over a prolonged follow-up, well-tolerated and effective approach for KS.
Co-administration of protease inhibitors with anticancer drugs in the management of HIV-related malignancies can cause potential drug-drug interactions. A study  conducted at the CRO-National Cancer Institute-Aviano, investigated the effect of lopinavir/ritonavir (LPV/RTV) on the pharmacokinetics of irinotecan (CPT11). Implications of this study were that the exposure to CPT11 was altered in patients under HAART regimens, including LPV/RTV (and potentially other protease inhibitors with enzyme inhibitory properties).
Although KS treatment is based on HAART, in rare cases individuals may experience KS flare during immune reconstitution inflammatory syndrome (IRIS), a heterogeneous and sometimes fatal disorder of immune perturbation after initiation of highly active antiretroviral therapy. Such a flare does not necessarily indicate a poor prognosis. Maserati reported a study  based on 9 HIV-infected patients with KS flare after virologic and immunologic response to HAART, and 10 cases identified by computerized search of the medical literature. Systemic chemotherapy, administered in 10 of 19 cases, led to tumor regression. Even for those patients with rapidly symptomatic KS, early systemic chemotherapy was effective in suppressing IRIS-associated flare.
- Pasini E, Caggiari L, Dal Maso L, Martorelli D, Guidoboni M, Vaccher E, Barzan L, Franchin G, Gloghini A, De Re V, et al: Undifferentiated nasopharyngeal carcinoma from a nonendemic area: protective role of HLA allele products presenting conserved EBV epitopes. Int J Cancer. 2009, 125: 1358-1364. 10.1002/ijc.24515.PubMedView ArticleGoogle Scholar
- Parkin DM: The global health burden of infection-associated cancers in the year 2002. Int J Cancer. 2006, 118: 3030-3044. 10.1002/ijc.21731.PubMedView ArticleGoogle Scholar
- Li N, Franceschi S, Howell-Jones R, Snijders PJ, Clifford GM: Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: Variation by geographical region, histological type and year of publication. Int J Cancer. 2011, 128: 927-935. 10.1002/ijc.25396.PubMedView ArticleGoogle Scholar
- Attner P, Du J, Näsman A, Hammarstedt L, Ramqvist T, Lindholm J, Marklund L, Dalianis T, Munck-Wikland E: Human papillomavirus and survival in patients with base of tongue cancer. Int J Cancer. 2011, 128: 2892-2897. 10.1002/ijc.25625.PubMedView ArticleGoogle Scholar
- Licitra L, Perrone F, Bossi P, Suardi S, Mariani L, Artusi R, Oggionni M, Rossini C, Cantù G, Squadrelli M, et al: High-risk human papillomavirus affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma. J Clin Oncol. 2006, 24: 5630-5636. 10.1200/JCO.2005.04.6136.PubMedView ArticleGoogle Scholar
- Perrone F, Gloghini A, Cortelazzi B, Bossi P, Licitra L, Pilotti S: Isolating p16-positive/HPV-negative oropharyngeal cancer: an effort worth making. Am J Surg Pathol. 2011, 35: 774-777.PubMedView ArticleGoogle Scholar
- Bello BD, Spinillo A, Alberizzi P, Cesari S, Gardella B, D'Ambrosio G, Roccio M, Silini EM: Cervical infections by multiple human papillomavirus (HPV) genotypes: Prevalence and impact on the risk of precancerous epithelial lesions. J Med Virol. 2009, 81: 703-712. 10.1002/jmv.21429.PubMedView ArticleGoogle Scholar
- Dal Bello B, Spinillo A, Alberizzi P, Cesari S, Gardella B, Silini EM: Validation of the SPF10 LiPA human papillomavirus typing assay using formalin-fixed paraffin-embedded cervical biopsy samples. J Clin Microbiol. 2009, 47: 2175-2180. 10.1128/JCM.00286-09.PubMedPubMed CentralView ArticleGoogle Scholar
- Dal Bello B, Spinillo A, Alberizzi P, Cesari S, Gardella B, Silini EM: Time trends of human papillomavirus type distribution in Italian women with cervical intraepithelial neoplasia (CIN). Gynecol Oncol. 2009, 115: 262-266. 10.1016/j.ygyno.2009.07.029.PubMedView ArticleGoogle Scholar
- Bruno S, Crosignani A, Maisonneuve P, Rossi S, Silini E, Mondelli MU: Hepatitis C virus genotype 1b as a major risk factor associated with hepatocellular carcinoma in patients with cirrhosis: a seventeen-year prospective cohort study. Hepatology. 2007, 46: 1350-1356. 10.1002/hep.21826.PubMedView ArticleGoogle Scholar
- Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, et al: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008, 359: 378-390. 10.1056/NEJMoa0708857.PubMedView ArticleGoogle Scholar
- Himmelsbach K, Sauter D, Baumert TF, Ludwig L, Blum HE, Hildt E: New aspects of an anti-tumour drug: sorafenib efficiently inhibits HCV replication. Gut. 2009, 58: 1644-1653. 10.1136/gut.2009.182212.PubMedView ArticleGoogle Scholar
- Martini F, De Mattei M, Iaccheri L, Lazzarin L, Barbanti-Brodano G, Tognon M, Gerosa M: Human brain tumors and simian virus 40. J Natl Cancer Inst. 1995, 87: 1331-PubMedView ArticleGoogle Scholar
- Martini F, Iaccheri L, Lazzarin L, Carinci P, Corallini A, Gerosa M, Iuzzolino P, Barbanti-Brodano G, Tognon M: SV40 early region and large T antigen in human brain tumors, peripheral blood cells, and sperm fluids from healthy individuals. Cancer Res. 1996, 56: 4820-4825.PubMedGoogle Scholar
- Feng H, Shuda M, Chang Y, Moore PS: Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 2008, 319: 1096-1100. 10.1126/science.1152586.PubMedPubMed CentralView ArticleGoogle Scholar
- Shuda M, Feng H, Kwun HJ, Rosen ST, Gjoerup O, Moore PS, Chang Y: T antigen mutations are a human tumor-specific signature for Merkel cell polyomavirus. Proc Natl Acad Sci U S A. 2008, 105: 16272-16277. 10.1073/pnas.0806526105.PubMedPubMed CentralView ArticleGoogle Scholar
- Touzé A, Gaitan J, Arnold F, Cazal R, Fleury MJ, Combelas N, Sizaret PY, Guyetant S, Maruani A, Baay M, et al: Generation of Merkel cell polyomavirus (MCV)-like particles and their application to detection of MCV antibodies. J Clin Microbiol. 2010, 48: 1767-1770. 10.1128/JCM.01691-09.PubMedPubMed CentralView ArticleGoogle Scholar
- Touzé A, Le Bidre E, Laude H, Fleury MJ, Cazal R, Arnold F, Carlotti A, Maubec E, Aubin F, Avril MF, et al: High levels of antibodies against Merkel cell polyomavirus identify a subset of patients with Merkel cell carcinoma with better clinical outcome. J Clin Oncol. 2011, 29: 1612-1619. 10.1200/JCO.2010.31.1704.PubMedView ArticleGoogle Scholar
- Pancaldi C, Corazzari V, Maniero S, Mazzoni E, Comar M, Martini F, Tognon M: Merkel cell polyomavirus DNA sequences in the buffy coats of healthy blood donors. Blood. 2011, 117: 7099-7101. 10.1182/blood-2010-09-310557.PubMedView ArticleGoogle Scholar
- Comar M, Rizzardi C, de Zotti R, Melato M, Bovenzi M, Butel JS, Campello C: SV40 multiple tissue infection and asbestos exposure in a hyperendemic area for malignant mesothelioma. Cancer Res. 2007, 67: 8456-8459. 10.1158/0008-5472.CAN-07-2232.PubMedView ArticleGoogle Scholar
- Campello C, Comar M, Zanotta N, Minicozzi A, Rodella L, Poli A: Detection of SV40 in colon cancer: a molecular case–control study from northeast Italy. J Med Virol. 2010, 82: 1197-1200. 10.1002/jmv.21798.PubMedView ArticleGoogle Scholar
- Campello C, Comar M, D'Agaro P, Minicozzi A, Rodella L, Poli A: A molecular case–control study of the Merkel cell polyomavirus in colon cancer. J Med Virol. 2011, 83: 721-724. 10.1002/jmv.22004.PubMedView ArticleGoogle Scholar
- Belingheri M, Comoli P, Locatelli F, Baldanti F, Martina V, Giani M, Ferraresso M, Cro L, Edefonti A, Ghio L: Successful medical treatment of EBV smooth muscle tumor in a renal transplant recipient. Pediatr Transplant. 2010, 14: E101-104. 10.1111/j.1399-3046.2009.01213.x.PubMedView ArticleGoogle Scholar
- Baldanti F, Rognoni V, Cascina A, Oggionni T, Tinelli C, Meloni F: Post-transplant lymphoproliferative disorders and Epstein-Barr virus DNAemia in a cohort of lung transplant recipients. Virol J. 2011, 8: 421-10.1186/1743-422X-8-421.PubMedPubMed CentralView ArticleGoogle Scholar
- Villa LL, Costa RL, Petta CA, Andrade RP, Ault KA, Giuliano AR, Wheeler CM, Koutsky LA, Malm C, Lehtinen M, et al: Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol. 2005, 6: 271-278. 10.1016/S1470-2045(05)70101-7.PubMedView ArticleGoogle Scholar
- Harper DM, Franco EL, Wheeler C, Ferris DG, Jenkins D, Schuind A, Zahaf T, Innis B, Naud P, De Carvalho NS, et al: Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet. 2004, 364: 1757-1765. 10.1016/S0140-6736(04)17398-4.PubMedView ArticleGoogle Scholar
- Schiffman M, Clifford G, Buonaguro FM: Classification of weakly carcinogenic human papillomavirus types: addressing the limits of epidemiology at the borderline. Infect Agent Cancer. 2009, 4: 8-10.1186/1750-9378-4-8.PubMedPubMed CentralView ArticleGoogle Scholar
- Tornesello ML, Loquercio G, Tagliamonte M, Rossano F, Buonaguro L, Buonaguro FM: Human papillomavirus infection in urine samples from male renal transplant patients. J Med Virol. 2010, 82: 1179-1185. 10.1002/jmv.21784.PubMedView ArticleGoogle Scholar
- Bruno S, Stroffolini T, Colombo M, Bollani S, Benvegnù L, Mazzella G, Ascione A, Santantonio T, Piccinino F, Andreone P, et al: Sustained virological response to interferon-alpha is associated with improved outcome in HCV-related cirrhosis: a retrospective study. Hepatology. 2007, 45: 579-587. 10.1002/hep.21492.PubMedView ArticleGoogle Scholar
- Bruno S, Zuin M, Crosignani A, Rossi S, Zadra F, Roffi L, Borzio M, Redaelli A, Chiesa A, Silini EM, et al: Predicting mortality risk in patients with compensated HCV-induced cirrhosis: a long-term prospective study. Am J Gastroenterol. 2009, 104: 1147-1158. 10.1038/ajg.2009.31.PubMedView ArticleGoogle Scholar
- Iacobellis A, Siciliano M, Perri F, Annicchiarico BE, Leandro G, Caruso N, Accadia L, Bombardieri G, Andriulli A: Peginterferon alfa-2b and ribavirin in patients with hepatitis C virus and decompensated cirrhosis: a controlled study. J Hepatol. 2007, 46: 206-212. 10.1016/j.jhep.2006.08.020.PubMedView ArticleGoogle Scholar
- Bruno S, Crosignani A, Facciotto C, Rossi S, Roffi L, Redaelli A, de Franchis R, Almasio PL, Maisonneuve P: Sustained virologic response prevents the development of esophageal varices in compensated, Child-Pugh class A hepatitis C virus-induced cirrhosis. A 12-year prospective follow-up study. Hepatology. 2010, 51: 2069-2076. 10.1002/hep.23528.PubMedView ArticleGoogle Scholar
- Roffi L, Colloredo G, Pioltelli P, Bellati G, Pozzpi M, Parravicini P, Bellia V, Del Poggio P, Fornaciari G, Ceriani R, et al: Pegylated interferon-alpha2b plus ribavirin: an efficacious and well-tolerated treatment regimen for patients with hepatitis C virus related histologically proven cirrhosis. Antivir Ther. 2008, 13: 663-673.PubMedGoogle Scholar
- Comoli P, Zecca M, Maccario R: Immunotherapy against EBV-lymphoma in recipients of HSCT. Expert Rev Hematol. 2010, 3: 625-632. 10.1586/ehm.10.56.PubMedView ArticleGoogle Scholar
- Comoli P, Basso S, Zecca M, Pagliara D, Baldanti F, Bernardo ME, Barberi W, Moretta A, Labirio M, Paulli M, et al: Preemptive therapy of EBV-related lymphoproliferative disease after pediatric haploidentical stem cell transplantation. Am J Transplant. 2007, 7: 1648-1655. 10.1111/j.1600-6143.2007.01823.x.PubMedView ArticleGoogle Scholar
- Comoli P, Basso S, Labirio M, Baldanti F, Maccario R, Locatelli F: T cell therapy of epstein-barr virus and adenovirus infections after hemopoietic stem cell transplant. Blood Cells Mol Dis. 2008, 40: 68-70. 10.1016/j.bcmd.2007.06.020.PubMedView ArticleGoogle Scholar
- Comoli P, Pedrazzoli P, Maccario R, Basso S, Carminati O, Labirio M, Schiavo R, Secondino S, Frasson C, Perotti C, et al: Cell therapy of stage IV nasopharyngeal carcinoma with autologous epstein-barr virus-targeted cytotoxic T lymphocytes. J Clin Oncol. 2005, 23: 8942-8949. 10.1200/JCO.2005.02.6195.PubMedView ArticleGoogle Scholar
- Secondino S, Zecca M, Licitra L, Gurrado A, Schiavetto I, Bossi P, Locati L, Schiavo R, Basso S, Baldanti F, et al: T-cell therapy for EBV-associated nasopharyngeal carcinoma: preparative lymphodepleting chemotherapy does not improve clinical results. Ann Oncol. 2012, 23: 435-441. 10.1093/annonc/mdr134.PubMedView ArticleGoogle Scholar
- Dal Maso L, Polesel J, Serraino D, Lise M, Piselli P, Falcini F, Russo A, Intrieri T, Vercelli M, Zambon P, et al: Pattern of cancer risk in persons with AIDS in Italy in the HAART era. Br J Cancer. 2009, 100: 840-847. 10.1038/sj.bjc.6604923.PubMedPubMed CentralView ArticleGoogle Scholar
- Polesel J, Franceschi S, Suligoi B, Crocetti E, Falcini F, Guzzinati S, Vercelli M, Zanetti R, Tagliabue G, Russo A, et al: Cancer incidence in people with AIDS in Italy. Int J Cancer. 2010, 127: 1437-1445. 10.1002/ijc.25153.PubMedView ArticleGoogle Scholar
- Puoti M, Bruno R, Soriano V, Donato F, Gaeta GB, Quinzan GP, Precone D, Gelatti U, Asensi V, Vaccher E, Group HHCI-S: Hepatocellular carcinoma in HIV-infected patients: epidemiological features, clinical presentation and outcome. AIDS. 2004, 18: 2285-2293. 10.1097/00002030-200411190-00009.PubMedView ArticleGoogle Scholar
- Berretta M, Garlassi E, Cacopardo B, Cappellani A, Guaraldi G, Cocchi S, De Paoli P, Lleshi A, Izzi I, Torresin A, et al: Hepatocellular carcinoma in HIV-infected patients: check early, treat hard. Oncologist. 2011, 16: 1258-1269. 10.1634/theoncologist.2010-0400.PubMedPubMed CentralView ArticleGoogle Scholar
- Guiguet M, Boué F, Cadranel J, Lang JM, Rosenthal E, Costagliola D, Cohort CEGotF AC: Effect of immunodeficiency, HIV viral load, and antiretroviral therapy on the risk of individual malignancies (FHDH-ANRS CO4): a prospective cohort study. Lancet Oncol. 2009, 10: 1152-1159. 10.1016/S1470-2045(09)70282-7.PubMedView ArticleGoogle Scholar
- Bihl F, Mosam A, Henry LN, Chisholm JV, Dollard S, Gumbi P, Cassol E, Page T, Mueller N, Kiepiela P, et al: Kaposi's sarcoma-associated herpesvirus-specific immune reconstitution and antiviral effect of combined HAART/chemotherapy in HIV clade C-infected individuals with Kaposi's sarcoma. AIDS. 2007, 21: 1245-1252. 10.1097/QAD.0b013e328182df03.PubMedView ArticleGoogle Scholar
- Bower M, Weir J, Francis N, Newsom-Davis T, Powles S, Crook T, Boffito M, Gazzard B, Nelson M: The effect of HAART in 254 consecutive patients with AIDS-related Kaposi's sarcoma. AIDS. 2009, 23: 1701-1706. 10.1097/QAD.0b013e32832d080d.PubMedView ArticleGoogle Scholar
- Corona G, Vaccher E, Sandron S, Sartor I, Tirelli U, Innocenti F, Toffoli G: Lopinavir-ritonavir dramatically affects the pharmacokinetics of irinotecan in HIV patients with Kaposi's sarcoma. Clin Pharmacol Ther. 2008, 83: 601-606. 10.1038/sj.clpt.6100330.PubMedView ArticleGoogle Scholar
- Leidner RS, Aboulafia DM: Recrudescent Kaposi's sarcoma after initiation of HAART: a manifestation of immune reconstitution syndrome. AIDS Patient Care STDS. 2005, 19: 635-644. 10.1089/apc.2005.19.635.PubMedView ArticleGoogle Scholar
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