Incidence trends of vulvar squamous cell carcinoma in Italy from 1990 to 2015.

OBJECTIVE: The incidence of vulvar squamous cell carcinoma has increased for decades in most Western countries - a trend virtually restricted to women aged <50 or 60 years. In southern Europe, conversely, the trends have been insufficiently studied. This article reports a study from Italy. METHOD: Thirty-eight local cancer registries, currently covering 15,274,070 women, equivalent to 49.2% of the Italian national female population, participated. Invasive cancers registered between 1990 and 2015 with an International Classification of Diseases for Oncology, 3rd revision, topography code C51 and morphology codes compatible with vulvar squamous cell carcinoma (n = 6294) were eligible. Incidence trends were analysed using joinpoint regression models, with calculation of the estimated annual percent change (EAPC), and age-period-cohort models. RESULTS: Total incidence showed a regular and significant decreasing trend (EAPC, -0.96; 95% confidence interval (CI), -1.43 to -0.48). This was entirely accounted for by women aged ≥60 years (EAPC, -1.34; 95% CI, -1.86 to -0.81). For younger women, the EAPC between 1990 and 2012 was 1.20 (95% CI, 0.34 to 2.06) with a non-significant acceleration thereafter. This pattern did not vary substantially in a sensitivity analysis for the effect of geographic area and duration of the registry. The age-period-cohort analysis revealed a risk decrease in cohorts born between 1905 and 1940 and a new increase in cohorts born since 1945. CONCLUSIONS: The decreasing trend observed among older women and the resulting decrease in total rate are at variance with reports from most Western countries. Age-period-cohort analysis confirmed a decreasing trend for earliest birth cohorts and an opposite one for recent ones.

Prognosis and cure of long-term cancer survivors: A population-based estimation.

BACKGROUND: Increasing evidence of cure for some neoplasms has emerged in recent years. The study aimed to estimate population-based indicators of cancer cure. METHODS: Information on more than half a million cancer patients aged 15-74 years collected by population-based Italian cancer registries and mixture cure models were used to estimate the life expectancy of fatal tumors (LEFT), proportions of patients with similar death rates of the general population (cure fraction), and time to reach 5-year conditional relative survival (CRS) >90% or 95% (time to cure). RESULTS: Between 1990 and 2000, the median LEFT increased >1 year for breast (from 8.1 to 9.4 years) and prostate cancers (from 5.2 to 7.4 years). Median LEFT in 1990 was >5 years for testicular cancers (5.8) and Hodgkin lymphoma (6.3) below 45 years of age. In both sexes, it was ≤0.5 years for pancreatic cancers and NHL in 1990 and in 2000. The cure fraction showed a 10% increase between 1990 and 2000. It was 95% for thyroid cancer in women, 94% for testis, 75% for prostate, 67% for breast cancers, and <20% for liver, lung, and pancreatic cancers. Time to 5-year CRS >95% was <10 years for testis, thyroid, colon cancers, and melanoma. For breast and prostate cancers, the 5-year CRS >90% was reached in <10 years but a small excess remained for >15 years. CONCLUSIONS: The study findings confirmed that several cancer types are curable. Became aware of the possibility of cancer cure has relevant clinical and social impacts.

The impact of overdiagnosis on thyroid cancer epidemic in Italy,1998-2012.

AIMS: In Italy, incidence rates of thyroid cancer (TC) are among the highest worldwide with substantial intracountry heterogeneity. The aim of the study was to examine time trends of TC incidence in Italy and to estimate the proportion of TC cases potentially attributable to overdiagnosis. METHODS: Data on TC cases reported to Italian cancer registries during 1998-2012 aged <85 years were included. Age-standardised incidence rates (ASR) were computed by sex, period, and histology. TC overdiagnosis was estimated by sex, period, age, and Italian region. RESULTS: In Italy between 1998-2002 and 2008-2012, TC ASR increased of 74% in women (from 16.2 to 28.2/100,000) and of 90% in men (from 5.3 to 10.1/100,000). ASR increases were nearly exclusively due to papillary TC (+91% in women, +120% in men). In both sexes, more than three-fold differences emerged between regions with highest and lowest ASR. Among TC cases diagnosed in 1998-2012 in Italy, we estimated that overdiagnosis accounted for 75% of cases in women and 63% in men and increased over the study period leading to overdiagnosis of 79% in women and 67% in men in 2008-2012. Notably, overdiagnosis was over 80% among women aged <55 years, and substantial variations were documented across Italian regions, in both genders. CONCLUSION(S): Incidence rates of TC are steadily increasing in Italy and largely due to overdiagnosis. These findings call for an update of thyroid gland examination practices in the asymptomatic general population, at national and regional levels.

Epidemiology and genetic susceptibility of malignant melanoma in North Sardinia, Italy.

The aim of this report was to study the descriptive and genetic epidemiology of malignant melanoma in North Sardinia, Italy, in the period 1992-2011. Epidemiological data were obtained from the local tumor registry, which is part of the Italian Association for Tumor Registries. Among patients included in the North Sardinia tumor registry, 316 patients first evaluated for familial recurrence of melanoma were submitted to mutation analysis in CDKN2A and CDK4 genes. The overall number of cases registered was 532. The male-to-female ratio was 1 : 1 and the mean age was 56 years for men and 55 years for women. The standardized incidence rates were 4.9/100 000 and 4.4/100 000 and the standardized mortality rates were 1.7/100 000 and 1.3/100 000 for men and women, respectively. The relative 5-year survival was 77% for men and 79% for women. In our series, 24/316 (7.6%) patients had a familial occurrence of melanoma (presence of at least one additional family member affected). Among these, one variant (Gly23Asp), reported previously as a low-frequency disease-causing mutation, was detected by mutational screening in the p16 gene only. With the exception of polymorphisms, none of either the sporadic melanoma patients or healthy controls presented a germline mutation in candidate genes. An increase in incidence and a decrease in mortality rates of malignant melanoma were registered in North Sardinia, from 1992 to 2011, whereas survival was similar to that reported in recent international reports. The high-penetrance melanoma susceptibility genes (CDKN2A and CDK4) are not involved in predisposition to melanoma in North Sardinia.

Disease presentation, treatment and survival for Italian colorectal cancer patients: a EUROCARE high resolution study.

We analysed presentation, treatment and survival in a representative population-based sample of 3753 Italian colorectal cancer cases, diagnosed 2003-05: 70% were >65 years, 44% stage I-II, 27% stage IV and 92% received surgery. Chemotherapy was given to 58% of stage III colon cases, radiotherapy to 25% of rectal cases. Four percent of surgical cases underwent endoscopic polypectomy, and in 57% ≥11 lymph nodes were examined. Five-year relative survival was good (60%), independent of sex and site. Adherence to treatment guidelines was satisfactory, but wider use of faecal blood testing and colonoscopy will anticipate stage at diagnosis and likely improve survival.

Epidemiology of malignant pleural mesothelioma in the province of Sassari (Sardinia, Italy). A population-based report.

UNLABELLED: The aim of this population-based study was to analyze and describe the epidemiological characteristics and trends of malignant pleural mesothelioma in the province of Sassari (Sardinia, Italy), in the period 1992-2010. Data were obtained from the local tumor registry which makes part of a wider registry web, coordinated today by the Italian Association for Tumor Registries. The overall number of malignant pleural mesothelioma cases registered was 70. The male-to-female ratio was 4:1 and the mean age 65.1 years for males and 63.4 years for females. The standardized incidence rates were 1.2/100,000 and 0.3/100,000 and the standardized mortality rates 0.6/100,000 and 0.2/100,000 for males and females respectively. A trend to increase in incidence in recent years was evidenced. This trend seems to follow the general national tendency and it depends on a large diffusion of asbestos usage in the past, delayed legislative interventions and probably a cleaning strategy of residual contamination fonts to intensify. The relative 5 years survival was low, suggesting the necessity to further intensify research and cure methods for the treatment of this extremely aggressive disease. KEY WORDS: Asbestos exposure, Mesothelioma, Pleura, Sassari.

High fasting blood glucose and obesity significantly and independently increase risk of breast cancer death in hormone receptor-positive disease.

PURPOSE: We investigated the effect of fasting blood glucose and body mass index (BMI) at diagnosis on risk of breast cancer death for cases diagnosed in five Italian cancer registries in 2003-2005 and followed up to the end of 2008. METHODS: For 1607 Italian women (≥15 years) with information on BMI or blood glucose or diabetes, we analysed the risk of breast cancer death in relation to glucose tertiles (≤84.0, 84.1-94.0, >94.0 mg/dl) plus diabetic and unspecified categories; BMI tertiles (≤23.4, 23.5-27.3, >27.3 kg/m(2), unspecified), stage (T1-3N0M0, T1-3N+M0 plus T4anyNM0, M1, unspecified), oestrogen (ER) and progesterone (PR) status (ER+PR+, ER-PR-, ER and PR unspecified, other), age, chemotherapy and endocrine therapy, using multiple regression models. Separate models for ER+PR+ and ER-PR- cases were also run. RESULTS: Patients often had T1-3N0M0, ER+PR+ cancers and received chemotherapy or endocrine therapy; only 6% were M1 and 17% ER-PR-. Diabetic patients were older and had more often high BMI (>27 kg/m(2)), ER-PR-, M1 cancers than other patients. For ER+PR+ cases, with adjustment for other variables, breast cancer mortality was higher in women with high BMI than those with BMI 23.5-27.3 kg/m(2) (hazard ratio (HR)=2.9, 95% confidence interval (CI) 1.2-6.9). Breast cancer mortality was also higher in women with high (>94 mg/dl) blood glucose compared to those with glucose 84.1-94.0mg/dl (HR=2.6, 95% CI 1.2-5.7). CONCLUSION: Our results provide evidence that in ER+PR+ patients, high blood glucose and high BMI are independently associated with increased risk of breast cancer death. Detection and correction of these factors in such patients may improve prognosis.

Lung cancer epidemiology in North Sardinia, Italy.

BACKGROUND: The aim of this study was to analyze and describe the epidemiological characteristics and trends of lung cancer in North Sardinia, Italy, in the period 1992-2010. METHODS: Data were obtained from the tumor registry of Sassari province which is a part of a wider registry web, coordinated today by the Italian Association for Tumor Registries. RESULTS: The overall number of lung cancer cases registered was 4,325. The male-to-female ratio was 4.6:1 and the mean age 68.1 years for males and 67 years for females. The standardized incidence rates were 73.1/100,000 and 13.5/100,000 and the standardized mortality rates 55.7/100,000 and 9.9/100,000 for males and females, respectively. An increasing trend in incidence of lung cancer in women was evidenced. Conversely, incidence was found to decrease in males. Relative survival at 5 years from diagnosis was low (8.8% for males and 14.9% for females). Furthermore, an increase in mortality rates was observed in both sexes in the period under investigation. CONCLUSIONS: Our data show an increasing trend of lung cancer incidence in women in North Sardinia in the last decades. Conversely, a reduction of incidence rates was observed in males. Furthermore, a slightly increasing trend in mortality rates was observed in both sexes, suggesting the need to enhance smoking control strategies, consider adoption of effective surveillance policies, and improve diagnosis and treatment methods.

Relative and disease-free survival for breast cancer in relation to subtype: a population-based study.

PURPOSE: No population-based study has investigated breast cancer (BC) subtypes defined by including Ki67. The aim of this study was to evaluate the relative proportions of immunohistochemical subtypes and differences in relative and disease-free survival between subtypes, in relation to patient and other cancer characteristics in Italian BC patient. METHODS: Information on estrogen, progesterone, human epidermal growth factor (HER2), Ki67, and relapses was obtained for 3,381 cases, sampled randomly and anonymously from cases diagnosed in 2003-2005 in nine Italian cancer registries. Relative excess risks (RERs) of death and risks of relapse 5 years after diagnosis were estimated. RESULTS: Luminal A cancers were 42 % of the total, luminal B 27 %, luminal-HER2 14 %, triple-negative 11 %, and HER2-enriched 7 %. For non-metastatic (3,302) cases, 4 and 7 % developed locoregional and distant metastases, respectively. RERs of death and risks of relapse were significantly greater for all cancer subtypes than luminal A, particularly for triple-negative and HER2-enriched cancers, which were more frequent in women <40 years. CONCLUSIONS: Our population-based findings confirm that subtype is an independent prognostic factor for BC. Triple-negative and HER2-enriched subtypes would benefit from the development and wide application, respectively, of targeted treatments, which would also improve survival for younger patients.

Epidemiology of thyroid cancer in an area of epidemic thyroid goiter.

The aim of this study was to analyze and describe the epidemiological characteristics and trends of thyroid cancer in the province of Sassari (Sardinia, Italy), an area with epidemic thyroid goiter, in the period 1992-2010. Data were obtained from the local tumor registry which makes part of a wider registry web, coordinated today by the Italian Association for Tumor Registries. An increasing trend in the incidence of thyroid cancer in the province of Sassari was evidenced. This trend seems to follow the general worldwide trend and does not seem to be related to the high incidence of thyroid goiter in the area. The frequencies of the different histological subtypes were similar to those reported in numerous national and international reports. Women are affected earlier than men and, therefore, suffer greater professional, economic, and social impacts. Overall mortality is low and a relative 5-year survival is excellent, especially in comparison to other malignancies.

Looking at differences in stage and treatment of colorectal cancers across Italy: a EUROCARE-5 high resolution study.

AIMS AND BACKGROUND: The high incidence and the estimate of a five-year relative survival of 59% for colorectal cancer in Italy were the main reasons to investigate the management of Italian patients with colorectal cancer diagnosed in the early 2000s. METHODS: Samples of adult (≥15 years) patients diagnosed in 2003-2005 with a colorectal cancer were randomly selected in 8 Italian population-based cancer registries. The z test was used to evaluate differences in proportions of Dukes stage, patients with at least 12 examined lymph nodes, and of cases treated with curative surgery plus chemotherapy or plus radiotherapy and diagnosed with colon or rectal tumors, respectively. Logistic regression models were used to estimate odds ratios of receiving the selected treatment in each cancer registry, age group and stage category, by anatomical subsite. RESULTS: A total of 3,938 colorectal cancer patients were analyzed. About 40% of the cases were over 75 years of age at diagnosis and at Dukes A + B stages. Higher proportions of early stages were found in the northern cancer registries. High percentages of resection with a curative intent were observed in Reggio Emilia (northern Italy), in 15 to 74-year-old patients, and at Dukes B stage. At least 12 lymph nodes were more frequently examined in the north of the country. After adjusting for age and stage, no significant differences were seen in the odds ratios of receiving surgery plus chemotherapy between cancer registries, whereas surgery plus radiotherapy was more frequent in Napoli (southern Italy) and less frequent in Biella (northern Italy). CONCLUSIONS: Some disparities in staging and treatment of colorectal cancer patients persist across Italy. National oncological plans still need to reduce inequalities in provision and access to proper care.

[Cancer incidence among petrochemical workers in the Porto Torres industrial area, 1990-2006]. / Incidenza di patologie neoplastiche nei lavoratori del complesso petrolchimico di Porto Torres, 1990-2006.

BACKGROUND: Various epidemiological studies explored cancer mortality and incidence among petrochemical workers. We followed up cancer incidence in a cohort of 5350 male petrochemical workers in the industrial area of Porto Torres (Sardinia, Italy). MATERIAL AND METHODS: The follow-up covered the period from 01/01/1990, when completeness of the cohort was certain and reference rates by the local Cancer Registry became available, up to 31/12/2006. Cohort members were subjects employed for six months or more in one of the chemical plants of the industrial area, alive as at 01/01/1990. Overall, a total of 81,392 person-years at risk were accumulated. The standardized incidence ratio (sir), as the ratio of observed to expected events, and its 95% confidence interval (CI) were calculated for all cancers and selected cancer sites, in the total cohort and in sub-cohorts of workers in plants where exposure to chemical agents evaluated in the IARC Monographs might have occurred. RESULTS: An increase in risk for all cancers was observed in the total cohort (596 cases; sir = 1.09; 95% CI 1.00-1.18), and it was highest for non-Hodgkin lymphoma (NHL, 26 cases: sir = 1.78; 95% CI 1.22-2.62). Risk for haemolymphatic cancer was highest in the sub-cohort of workers employed for 10 years or more, with a latency period of 20 years or longer, and among those employed in the manufacture and polymerization of vinyl chloride (VCM; all cancers, 51 cases: sir = 1.43; 95% CI 1.08-1.88; NHL, 4 cases: sir=4.06; 95% CI 1.64-10.0). Risk of haemolymphatic cancer was not significantly elevated in the sub-cohort potentially exposed to benzene. An excess risk of bladder cancer (RR = 1.46; 95% CI 1.09-1.96), but not of pleural cancer, was observed in the sub-cohort potentially exposed to asbestos. No significant increase in cancer risk was observed among workers potentially exposed to acrylonitrile, butadiene, or styrene. CONCLUSIONS: Our follow-up study of petrochemical workers showed an increase in risk for all cancers, and particularly NHL, apparently concentrated among workers potentially exposed to VCM

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.

Role of BRCA2 mutation status on overall survival among breast cancer patients from Sardinia.

BACKGROUND: Germline mutations in BRCA1 or BRCA2 genes have been demonstrated to increase the risk of developing breast cancer. Conversely, the impact of BRCA mutations on prognosis and survival of breast cancer patients is still debated. In this study, we investigated the role of such mutations on breast cancer-specific survival among patients from North Sardinia. METHODS: Among incident cases during the period 1997-2002, a total of 512 breast cancer patients gave their consent to undergo BRCA mutation screening by DHPLC analysis and automated DNA sequencing. The Hakulinen, Kaplan-Meier, and Cox regression methods were used for both relative survival assessment and statistical analysis. RESULTS: In our series, patients carrying a germline mutation in coding regions and splice boundaries of BRCA1 and BRCA2 genes were 48/512 (9%). Effect on overall survival was evaluated taking into consideration BRCA2 carriers, who represented the vast majority (44/48; 92%) of mutation-positive patients. A lower breast cancer-specific overall survival rate was observed in BRCA2 mutation carriers after the first two years from diagnosis. However, survival rates were similar in both groups after five years from diagnosis. No significant difference was found for age of onset, disease stage, and primary tumour histopathology between the two subsets. CONCLUSION: In Sardinian breast cancer population, BRCA2 was the most affected gene and the effects of BRCA2 germline mutations on patients' survival were demonstrated to vary within the first two years from diagnosis. After a longer follow-up observation, breast cancer-specific rates of death were instead similar for BRCA2 mutation carriers and non-carriers.

Strong seasonality in the diagnosis of skin melanoma in Italy: the Italian Network of Cancer Registries (AIRTUM) study.

AIM: To evaluate seasonality in the diagnosis of cutaneous melanoma in Italy. METHODS: A total of 16,284 invasive (and 1,235 in situ) cutaneous melanomas incident from 1978 to 2002 in 14 cancer registries belonging to the Italian Network of Cancer Registries (AIRTUM) was analyzed. We used the Walter and Elwood test to evaluate seasonality. The monthly distribution of diagnosis was evaluated for sex, skin site, melanoma morphology and period of diagnosis. RESULTS: The overall monthly diagnosis of invasive melanoma showed a statistically significant excess around the month of June. The same pattern was present for males and females, across age-groups and periods of time. All skin sites showed a cycling trend, melanoma of the head and neck peaked around April, all the others peaked around June. As regards morphologic types, a cyclic trend was evident for superficial-spreading melanomas (peak around July), for not-specified melanomas (June) and for other histotypes (June). Diagnosis of in situ melanoma peaked in September. CONCLUSIONS: The present study showed that also in Italy melanoma diagnosis has a seasonal trend, with the peak in early summer. It seemed that summer UV exposure, acting both as a late promoter of malignant melanoma development and also increasing the visibility of pigmented skin lesion, may be relevant to explain such a peak.

The risk of developing a second, different, cancer among 14 560 survivors of malignant cutaneous melanoma: a study by AIRTUM (the Italian Network of Cancer Registries).

The aim of this study was to provide further quantitative data on the risk of second nonmelanoma cancers in patients with cutaneous malignant melanoma (CMM). A cohort of 14 560 population-based patients from the Italian Network of Cancer Registries incident during 1985-2002 were included and followed up for further incident cases and vital status. Standardized incidence ratios (SIR) were used to compare the number of observed second cancers with expected cancers. In a total of 69 581 person-years, 1020 second cancers were registered, of which 804.6 were expected (SIR=1.27; 95% confidence interval 1.19-1.35). The risk was similar for males and females, (SIR=1.27 and 1.26, respectively). The risk was slightly higher among younger (<60 years; SIR=1.44) than older (60+ years; SIR=1.19) patients. The overall risk in the period after CMM diagnosis did not change significantly (SIR=1.34 during the first 5 years and 1.12 afterwards). No differences in the overall risk were evident in different years of diagnosis, for different melanoma morphology types or for different geographical areas within Italy. Statistically significantly increased risks were found for nonmelanoma skin cancers [observed number (n)=362, SIR=3.12], for bone (n=5, SIR=6.08) and for kidney cancers (n=39, SIR=1.95) and lower than expected risks were found for liver (SIR=0.46) and lung cancers (SIR=0.71). We confirm that CMM patients are at high risk for nonmelanoma skin cancers. The reasons for the increased risk of kidney and bone cancers are not yet clear.