Fabrizio Stracci

Pattern of cancer risk in persons with AIDS in Italy in the HAART era

A record-linkage study was carried out between the Italian AIDS Registry and 24 Italian cancer registries to compare cancer excess among persons with HIV/AIDS (PWHA) before and after the introduction of highly active antiretroviral therapy (HAART) in 1996. Standardised incidence ratios (SIR) were computed in 21951 AIDS cases aged 16–69 years reported between 1986 and 2005. Of 101 669 person-years available, 45 026 were after 1996. SIR for Kaposi sarcoma (KS) and non-Hodgkin lymphoma greatly decreased in 1997–2004 compared with 1986–1996, but high SIRs for KS persisted in the increasingly large fraction of PWHA who had an interval of <1 year between first HIV-positive test and AIDS diagnosis. A significant excess of liver cancer (SIR=6.4) emerged in 1997–2004, whereas the SIRs for cancer of the cervix (41.5), anus (44.0), lung (4.1), brain (3.2), skin (non-melanoma, 1.8), Hodgkin lymphoma (20.7), myeloma (3.9), and non-AIDS-defining cancers (2.2) were similarly elevated in the two periods. The excess of some potentially preventable cancers in PWHA suggests that HAART use must be accompanied by cancer-prevention strategies, notably antismoking and cervical cancer screening programmes. Improvements in the timely identification of HIV-positive individuals are also a priority in Italy to avoid the adverse consequences of delayed HAART use.

Estimate of overdiagnosis of breast cancer due to mammography after adjustment for lead time. A service screening study in Italy

IntroductionExcess of incidence rates is the expected consequence of service screening. The aim of this paper is to estimate the quota attributable to overdiagnosis in the breast cancer screening programmes in Northern and Central Italy.MethodsAll patients with breast cancer diagnosed between 50 and 74 years who were resident in screening areas in the six years before and five years after the start of the screening programme were included. We calculated a corrected-for-lead-time number of observed cases for each calendar year. The number of observed incident cases was reduced by the number of screen-detected cases in that year and incremented by the estimated number of screen-detected cases that would have arisen clinically in that year.ResultsIn total we included 13,519 and 13,999 breast cancer cases diagnosed in the pre-screening and screening years, respectively. In total, the excess ratio of observed to predicted in situ and invasive cases was 36.2%. After correction for lead time the excess ratio was 4.6% (95% confidence interval 2 to 7%) and for invasive cases only it was 3.2% (95% confidence interval 1 to 6%).ConclusionThe remaining excess of cancers after individual correction for lead time was lower than 5%.

Incidence of thyroid cancer in Italy, 1991–2005: time trends and age–period–cohort effects

BACKGROUND In Italy, some of the highest incidence rates (IRs) of thyroid cancer (TC) worldwide have been reported. PATIENTS AND METHODS TC cases <85 years of age reported to Italian cancer registries during 1991-2005 were included. Age-standardized IRs were computed for all TC and age-period-cohort effects were estimated for papillary TC. RESULTS IRs of TC were twofold higher in 2001-2005 than in 1991-1995 (18 and 8 per 100,000 women, 6 and 3 per 100,000 men, respectively). Increases were similar in the two sexes and nearly exclusively due to papillary TC. Increases of papillary TC by birth cohort were found in both sexes and among all age groups between 20 and 79 years. Age-period-cohort models showed a strong period effect in both sexes (rate ratio for 2001-2009 versus 1991-1995 = 2.5 in women and 2.3 in men), although IRs peaked at an earlier age in women (45-49 years) than men (65-69 years). CONCLUSION The strength of the period effect in both sexes and the earlier onset in women than men strongly implicated increased medical surveillance in the upward trends of papillary TC incidence in Italy. The consequences of the current intense search for TC on morbidity and possible overtreatment, especially among young women, should be carefully evaluated.

Cancer incidence in people with AIDS in Italy

People with HIV/AIDS (PWHA) have increased risk of some cancers. The introduction of highly active antiretroviral therapies (HAART) has improved their life expectancy, exposing them to the combined consequences of aging and of a prolonged exposure to cancer risk factors. The aim of this study was to estimate incidence rates (IR) in PWHA in Italy, before and after the introduction of HAART, after adjusting for sex and age through direct standardization. An anonymous record linkage between Italian AIDS Registry (21,951 cases) and Cancer Registries (17.3 million, 30% of Italian population) was performed. In PWHA, crude IR, sex‐ and age‐standardized IR and age‐specific IR were estimated. The standardized IR for Kaposi sarcoma and non‐Hodgkin lymphoma greatly declined in the HAART period. Although the crude IR for all non‐AIDS‐defining cancers increased in the HAART period, standardized IR did not significantly differ in the 2 periods (352 and 379/100,000, respectively). Increases were seen only for cancer of the liver (IR ratio = 4.6, 95% CI: 1.3–17.0) and lung (IR ratio = 1.8, 95% CI: 1.0–3.2). Age‐specific IRs for liver and lung cancers, however, largely overlapped in the 2 periods pointing to the strong influence of the shift in the age distribution of PWHA on the observed upward trends. In conclusion, standardized IRs for non‐AIDS‐defining cancers have not risen in the HAART period, even if crude IRs of these cancers increased. This scenario calls, however, for the intensification of cancer‐prevention strategies, notably smoking cessation and screening programs, in middle‐aged HIV‐patients.

Classic Kaposi's sarcoma in Italy, 1985-1998.

To evaluate incidence rates (IRs) of classic Kaposis sarcoma (CKS) in Italy after the spread of AIDS, we distinguished CKS from AIDS-related KS (AKS) using an ‘ad hoc’ record linkage procedure between 15 Cancer Registries (CRs) (21% of the Italian population) and the national AIDS Registry. Between 1985 and 1998, 874 cases of CKS and 634 cases of AKS were diagnosed in the study areas. CKS accounted for 16 and 27% of KS cases below 55 years of age in men and women, respectively, but for 91 and 100% of those above age 55. The IRs for CKS were 1.0/ in men and 0.4/100 000 in women, but they varied between 0.3 in Umbria and 4.7 in Sassari in men, and between 0.1 in Parma and 1.7 in Sassari in women. IRs of CKS in both genders were stable between 1985–1987 and 1993–1998. In Northern and Central CRs the IR (adjusted for age and gender) for CKS was 0.5 in individuals born in the same area, but 1.6 in individuals born in Southern Italy or in the Islands (rate ratio=3.2) suggesting that KS-associated herpesvirus, the cause of KS, is acquired early in life.

Colorectal Cancer Screening: Tests, Strategies, and Perspectives

Screening has a central role in colorectal cancer (CRC) control. Different screening tests are effective in reducing CRC-specific mortality. Influence on cancer incidence depends on test sensitivity for pre-malignant lesions, ranging from almost no influence for guaiac-based fecal occult blood testing (gFOBT) to an estimated reduction of 66–90% for colonoscopy. Screening tests detect lesions indirectly in the stool [gFOBT, fecal immunochemical testing (FIT), and fecal DNA] or directly by colonic inspection [flexible sigmoidoscopy, colonoscopy, CT colonography (CTC), and capsule endoscopy]. CRC screening is cost-effective compared to no screening but no screening strategy is clearly better than the others. Stool tests are the most widely used in worldwide screening interventions. FIT will soon replace gFOBT. The use of colonoscopy as a screening test is increasing and this strategy has superseded all alternatives in the US and Germany. Despite its undisputed importance, CRC screening is under-used and participation rarely reaches 70% of target population. Strategies to increase participation include ensuring recommendation by physicians, introducing organized screening and developing new, more acceptable tests. Available evidence for DNA fecal testing, CTC, and capsule endoscopy is reviewed.

Decreasing Incidence of Late-Stage Breast Cancer After the Introduction of Organized Mammography Screening in Italy

After the introduction of a mammography screening program, the incidence of late‐stage breast cancer is expected to decrease. The objective of the current study was to evaluate variations in the total incidence of breast cancer and in the incidence of breast cancers with a pathologic tumor (pT) classification of pT2 through pT4 after the introduction of mammography screening in 6 Italian administrative regions.

Diagnostic potential in prostate cancer of a panel of urinary molecular tumor markers

Prostate cancer (PCa) is a heterogeneous, multifactorial and multifocal disease. Therefore, the search for a combination of assays using a panel of tumor markers is fundamental for a more precise and reliable diagnosis. In the present study we investigated the diagnostic value of five different genes, associated with PCa carcinogenesis, encoding for prostate-specific membrane antigen (PSMA), serine protease Hepsin, PCa antigen 3 (PCA3), UDP-N-acetyl-alpha-D-galatosamine transferase (GalNAC-T3) and prostate-specific antigen (PSA). Forty-four patients, with previously untreated, histologically verified PCa and forty-six patients with benign prostatic hyperplasia (BPH) were enrolled in this study. Absolute concentration of the transcript levels of each gene was calculated by quantitative Real-Time PCR analysis in urine sediments of men suffering from PCa or BPH after prostatic massage. The diagnostic value of a concomitant examination of these markers was evaluated by logistic regression analysis. We demonstrated that the diagnostic potential of the combined urinary PSA and PSMA level was significantly better than that of each singularly considered marker, including total serum PSA, the present gold standard test for PCa diagnosis.

Malignant mesothelioma due to non-occupational asbestos exposure from the Italian national surveillance system (ReNaM): epidemiology and public health issues

Introduction Italy produced and imported a large amount of raw asbestos, up to the ban in 1992, with a peak in the period between 1976 and 1980 at about 160 000 tons/year. The National Register of Mesotheliomas (ReNaM, “Registro Nazionale dei Mesoteliomi” in Italian), a surveillance system of mesothelioma incidence, has been active since 2002, operating through a regional structure. Methods The Operating Regional Center (COR) actively researches cases and defines asbestos exposure on the basis of national guidelines. Diagnostic, demographic and exposure characteristics of non-occupationally exposed cases are analysed and described with respect to occupationally exposed cases. Results Standardised incidence rates for pleural mesothelioma in 2008 were 3.84 (per 100 000) for men and 1.45 for women, respectively. Among the 15 845 mesothelioma cases registered between 1993 and 2008, exposure to asbestos fibres was investigated for 12 065 individuals (76.1%), identifying 530 (4.4%) with familial exposure (they lived with an occupationally exposed cohabitant), 514 (4.3%) with environmental exposure to asbestos (they lived near sources of asbestos pollution and were never occupationally exposed) and 188 (1.6%) exposed through hobby-related or other leisure activities. Clusters of cases due to environmental exposure are mainly related to the presence of asbestos-cement industry plants (Casale Monferrato, Broni, Bari), to shipbuilding and repair activities (Monfalcone, Trieste, La Spezia, Genova) and soil contamination (Biancavilla in Sicily). Conclusions Asbestos pollution outside the workplace contributes significantly to the burden of asbestos-related diseases, suggesting the need to prevent exposures and to discuss how to deal with compensation rights for malignant mesothelioma cases induced by non-occupational exposure to asbestos.

A one-mutation mathematical model can explain the age incidence of acute myeloid leukemia with mutated nucleophosmin (NPM1).

Acute myeloid leukemia with mutated NPM1 gene and aberrant cytoplasmic expression of nucleophosmin shows distinctive biological and clinical features. Based on the use of a one-mutation mathematical model, this study supports the hypothesis that a single genetic event, the NPM1 mutation, is sufficient to cause this type of leukemia. Acute myeloid leukemia with mutated NPM1 gene and aberrant cytoplasmic expression of nucleophosmin (NPMc+ acute myeloid leukemia) shows distinctive biological and clinical features. Experimental evidence of the oncogenic potential of the nucleophosmin mutant is, however, still lacking, and it is unclear whether other genetic lesion(s), e.g. FLT3 internal tandem duplication, cooperate with NPM1 mutations in acute myeloid leukemia development. An analysis of age-specific incidence, together with mathematical modeling of acute myeloid leukemia epidemiology, can help to uncover the number of genetic events needed to cause leukemia. We collected data on age at diagnosis of acute myeloid leukemia patients from five European Centers in Germany, The Netherlands and Italy, and determined the age-specific incidence of AML with mutated NPM1 (a total of 1,444 cases) for each country. Linear regression of the curves representing age-specific rates of diagnosis per year showed similar slopes of about 4 on a double logarithmic scale. We then adapted a previously designed mathematical model of hematopoietic tumorigenesis to analyze the age incidence of acute myeloid leukemia with mutated NPM1 and found that a one-mutation model can explain the incidence curve of this leukemia entity. This model fits with the hypothesis that NPMc+ acute myeloid leukemia arises from an NPM1 mutation with haploinsufficiency of the wild-type NPM1 allele.