Immunodeficiency and the risk of cervical intraepithelial neoplasia 2/3 and cervical cancer: A nested case-control study in the Swiss HIV cohort study.

HIV-infected women are at increased risk of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC), but it has been difficult to disentangle the influences of heavy exposure to HPV infection, inadequate screening and immunodeficiency. A case-control study including 364 CIN2/3 and 20 ICC cases matched to 1,147 controls was nested in the Swiss HIV Cohort Study (1985-2013). CIN2/3 risk was significantly associated with low CD4+ cell counts, whether measured as nadir [odds ratio (OR) per 100-cell/µL decrease = 1.15, 95% CI: 1.08, 1.22], or at CIN2/3 diagnosis (1.10, 95% CI: 1.04, 1.16). An association was evident even for nadir CD4+ 200-349 versus ≥350 cells/µL (OR = 1.57, 95% CI: 1.09, 2.25). After adjustment for nadir CD4+, a protective effect of >2-year cART use was seen against CIN2/3 (OR versus never cART use = 0.64, 95% CI: 0.42, 0.98). Despite low study power, similar associations were seen for ICC, notably with nadir CD4+ (OR for 50 vs. >350 cells/µL= 11.10, 95% CI: 1.24, 100). HPV16-L1 antibodies were significantly associated with CIN2/3, but HPV16-E6 antibodies were nearly exclusively detected in ICC. In conclusion, worsening immunodeficiency, even at only moderately decreased CD4+ cell counts, is a significant risk factor for CIN2/3 and cervical cancer.

Risk factors for anal cancer in persons infected with HIV: a nested case-control study in the Swiss HIV Cohort Study.

Although persons infected with human immunodeficiency virus (HIV), particularly men who have sex with men, are at excess risk for anal cancer, it has been difficult to disentangle the influences of anal exposure to human papillomavirus (HPV) infection, immunodeficiency, and combined antiretroviral therapy. A case-control study that included 59 anal cancer cases and 295 individually matched controls was nested in the Swiss HIV Cohort Study (1988-2011). In a subset of 41 cases and 114 controls, HPV antibodies were tested. A majority of anal cancer cases (73%) were men who have sex with men. Current smoking was significantly associated with anal cancer (odds ratio (OR) = 2.59, 95% confidence interval (CI): 1.25, 5.34), as were antibodies against L1 (OR = 4.52, 95% CI: 2.00, 10.20) and E6 (OR = ∞, 95% CI: 4.64, ∞) of HPV16, as well as low CD4+ cell counts, whether measured at nadir (OR per 100-cell/µL decrease = 1.53, 95% CI: 1.18, 2.00) or at cancer diagnosis (OR per 100-cell/µL decrease = 1.24, 95% CI: 1.08, 1.42). However, the influence of CD4+ cell counts appeared to be strongest 6-7 years prior to anal cancer diagnosis (OR for <200 vs. ≥500 cells/µL = 14.0, 95% CI: 3.85, 50.9). Smoking cessation and avoidance of even moderate levels of immunosuppression appear to be important in reducing long-term anal cancer risks.

Body size and risk of differentiated thyroid carcinomas: findings from the EPIC study.

Results from case-control and prospective studies suggest a moderate positive association between obesity and height and differentiated thyroid carcinoma (TC). Little is known on the relationship between other measures of adiposity and differentiated TC risk. Here, we present the results of a study on body size and risk of differentiated TC based on a large European prospective study (EPIC). During follow-up, 508 incident cases of differentiated TC were identified in women, and 58 in men. 78% of cases were papillary TC. Cox proportional hazard models were used to estimate hazard ratios (HRs). In women, differentiated TC risk was significantly associated with body mass index (BMI, kg/m(2)) (HR highest vs lowest quintile = 1.41, 95% CI: 1.03-1.94); height (HR = 1.61; 95% CI: 1.18-2.20); HR highest vs lowest tertile waist (HR = 1.34, 95% CI: 1.00-1.79) and waist-to-hip ratio (HR = 1.42, 95% CI: 1.05-1.91). The association with BMI was somewhat stronger in women below age 50. Corresponding associations for papillary TC were similar to those for all differentiated TC. In men the only body size factors significantly associated with differentiated TC were height (non linear), and leg length (HR highest vs. lowest tertile = 3.03, 95% CI: 1.30-7.07). Our study lends further support to the presence of a moderate positive association between differentiated TC risk and overweight and obesity in women. The risk increase among taller individuals of both sexes suggests that some genetic characteristics or early environmental exposures may also be implicated in the etiology of differentiated TC.

Hodgkin lymphoma in the Swiss HIV Cohort Study.

Hodgkin lymphoma (HL) risk is elevated among persons infected with HIV (PHIV) and has been suggested to have increased in the era of combined antiretroviral therapy (cART). Among 14,606 PHIV followed more than 20 years in the Swiss HIV Cohort Study (SHCS), determinants of HL were investigated using 2 different approaches, namely, a cohort and nested case-control study, estimating hazard ratios (HRs) and matched odds ratios, respectively. Forty-seven incident HL cases occurred during 84,611 person-years of SHCS follow-up. HL risk was significantly higher among men having sex with men (HR vs intravenous drug users = 2.44, 95% confidence interval [CI], 1.13-5.24) but did not vary by calendar period (HR for 2002-2007 vs 1995 or earlier = 0.65, 95% CI, 0.29-1.44) or cART use (HR vs nonusers = 1.02, 95% CI, 0.53-1.94). HL risk tended to increase with declining CD4(+) cell counts, but these differences were not significant. A lower CD4(+)/CD8(+) ratio at SHCS enrollment or 1 to 2 years before HL diagnosis, however, was significantly associated with increased HL risk. In conclusion, HL risk does not appear to be increasing in recent years or among PHIV using cART in Switzerland, and there was no evidence that HL risk should be increased in the setting of improved immunity.

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.

Self-reported history of Pap-smear in HIV-positive women in Northern Italy: a cross-sectional study.

BACKGROUND: The incidence of invasive cervical cancer in HIV-positive women is higher than in the general population. There is evidence that HIV-positive women do not participate sufficiently in cervical cancer screening in Italy, where cervical cancer is more than 10-fold higher in women with AIDS than in the general population. The aim of the present study was to evaluate the history of Pap-smear in HIV-positive women in Italy in recent years. We also examined the sociodemographic, clinical, and organizational factors associated with adherence to cervical cancer screening. METHODS: A cross-sectional study was conducted between July 2006 and June 2007 in Emilia-Romagna region (Northern Italy). All HIV-positive women who received a follow-up visit in one of the 10 regional infectivology units were invited to participate. History of Pap-smear, including abnormal smears and subsequent treatment, was investigated through a self-administered anonymous questionnaire. The association between lack of Pap-smear in the year preceding the interview and selected characteristics was assessed by means of odds ratios (OR) and 95% confidence intervals adjusted for study centre and age. RESULTS: A total of 1,002 HIV-positive women were interviewed. Nine percent reported no history of Pap-smear, and 39% had no Pap-smear in the year prior to the date of questionnaire (last year). The lack of Pap-smear in the last year was significantly associated with age <35 years (OR = 1.4, compared to age > or =45 years), lower education level (OR = 1.3), first HIV-positive test in the last 2 years (OR = 1.4), and CD4 count <200 cells/microl (OR = 1.6). Conversely, when women were advised by a gynecologist rather than other health workers to undergo screening, it significantly increased adherence. Non-significantly higher proportions of lack of Pap-smear in the last year were found in women born in Central-Eastern Europe (OR = 1.8) and Africa (OR = 1.3). No difference in history of Pap-smear emerged by mode of HIV-acquisition or AIDS status.Three hundred five (34%) women reported a previous abnormal Pap-smear, and of the 178 (58%) referred for treatment, 97% complied. CONCLUSIONS: In recent years the self-reported history of Pap-smear in HIV-positive women, in some public clinics in Italy, is higher than previously reported, but further efforts are required to make sure cervical cancer screening is accessible to all HIV-positive women.

Incidence of primary liver cancer in Italy between 1988 and 2002: an age-period-cohort analysis.

We conducted in Italy a study to evaluate trends of primary liver cancer (PLC) and to disentangle the period from birth-cohort effects on PLC incidence. Cases aged<80 years and diagnosed between 1988 and 2002 in 20 areas covered by population-based Cancer Registries were included. Age-standardised incidence rates and age-period-cohort effects were estimated. In 1998-2002, incidence rates of PLC were 21.1/100,000 men and 6.0/100,000 women. In both genders, incidence rates increased slightly between 1988-1992 and 1993-1997 but did not rise thereafter. Amongst men, PLC risk increased in every cohort born after 1913 and the rise became steeper for cohorts born in 1948. In women, an upward trend appeared only in the cohorts born after 1953. Incidence of PLC over the last two decades in Italy did not substantially change but huge geographical variability emerged, mainly due to different times and modalities of spread of hepatitis C virus.

Detection and restaging of residual and/or recurrent nasopharyngeal carcinoma after chemotherapy and radiation therapy: comparison of MR imaging and FDG PET/CT.

PURPOSE: To compare the accuracy of magnetic resonance (MR) imaging and combined fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT), alone and in combination, in detection and restaging treated nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: This retrospective study was performed after institutional review board approval and informed consent were obtained. Sixty-three consecutive patients treated for NPC underwent follow-up with both MR imaging and FDG PET/CT. Findings were evaluated according to the TNM classification. Final diagnosis was confirmed at biopsy or imaging follow-up for at least 6 months. Proportions and their 95% confidence intervals were computed; for comparison of data obtained separately from MR imaging and FDG PET/CT and those obtained from their combined use, the McNemar test was used. P < .05 was considered to indicate a statistically significant difference. RESULTS: There was a trend toward greater overall accuracy of MR over PET/CT in detecting residual and/or recurrent NPC at the primary site; 92.1% (58 of 63 patients) for MR versus 85.7% (54 of 63) for FDG PET/CT (P = .16). Overall accuracy for tumor restaging was 74.6% (47 of 63) for MR and 73.0% (46 of 63) for FDG PET/CT (either modality used alone), but the overall combined accuracy was 92.1% (58 of 63) (all P values < .01). CONCLUSION: MR imaging demonstrated a trend toward higher accuracy than did FDG PET/CT in detecting residual and/or recurrent NPC at the primary tumor site. The combined use of MR and FDG PET/CT was more accurate for tumor restaging than when either modality was used independently.

Changes in the incidence of thyroid cancer between 1991 and 2005 in Italy: a geographical analysis.

BACKGROUND: The incidence of thyroid cancer (TC) has been increasing over the last 30 years in several countries, with some of the worldwide highest TC incidence rates (IRs) reported in Italy. The objectives of this study were to evaluate by histological subtypes the geographical heterogeneity of the incidence of TC in Italy and to analyze recent time trends for papillary thyroid carcinoma (PTC) in different cancer registries (CRs). METHODS: The study included cases of TC (<85 years of age) reported to 25 Italian CRs between 1991 and 2005. Age-standardized IRs were computed for all histological subtypes of TC according to CRs. Estimated annual percent change and joinpoint regression analysis were used for analysis of PTC. RESULTS: In women, IRs of PTC ranged between 3.5/100,000 in Latina and 8.5/100,000 in Sassari for the period 1991-1995 (a 2.4-fold difference) and between 7.3/100,000 in Alto Adige and 37.5/100,000 in Ferrara for 2001-2005 (a 5.1-fold difference). In men, IRs ranged between 0.7/100,000 in Latina and 3.4/100,000 in Sassari for the period 1991-1995 (a 4.9-fold difference) and between 2.0/100,000 (Alto Adige, Trento) and 10.6/100,000 in Ferrara for 2001-2005 (a 5.3-fold difference). In both sexes, IRs significantly higher than the pooled estimates emerged for the most recent period in the majority of CRs located within the Po River plain and in Latina, but they were lower in the Alpine belt. For women, CRs reported higher IRs than pool estimates showed, between 1991 to 2005, a significantly more marked annual percent change (+12%) than other CRs (+7%). For men the corresponding estimates were +11% and +8%. CONCLUSIONS: The distribution of PTC does not lend support to a role of environmental radiation exposure due to the Chernobyl fallout, iodine deficiency, or (volcanic) soils. Between 1991 and 2005, wide geographic variations in the incidence of PTC and heterogeneous upward trends emerged, suggesting that the heterogeneity was a relatively recent phenomenon; this appeared to be mainly explained by variations, at a local level, in medical surveillance.

Hepatitis B and C virus infections in hepatocellular carcinoma and cirrhosis in Mongolia.

The incidence of hepatocellular carcinoma (HCC) in Mongolia is far higher than that of any other cancer in the country, and among the highest worldwide. The relative importance of infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) is unclear. We reviewed (i) medical records for 963 patients with HCC and 941 patients with cirrhosis admitted for the first time to the National Cancer Center of Mongolia and the National Center for Communicable Diseases, respectively, from 2000 to 2009,and (ii) articles published from 1990 to 2010 on the seroprevalence of hepatitis B surface antigen (HBsAg) and antibodies against hepatitis C virus (anti-HCV) among individuals with and without liver disease. Among those with HCC, the seroprevalence of HBsAg, anti-HCV and dual infections was 50, 27 and 21%, respectively. Corresponding percentages among the patients with cirrhosis were 40, 39, and 20%. In both diseases, HCV infection was relatively more prevalent in women than in men and, in cirrhosis, inpatients older than 45 years of age. In healthy individuals,from published articles, anti-HCV seroprevalence steadily increased with age (from 3% at age 0-5 years to 34% at age ≥ 50 years), whereas HBsAg seroprevalence stayed constant at about 8%. The future benefit of childhood vaccination against HBV in Mongolia will be undermined by the consequences of a severe HCV epidemic and a uniquely high burden of dual infections.

Infection with hepatitis B and C viruses and risk of lymphoid malignancies in the European Prospective Investigation into Cancer and Nutrition (EPIC).

BACKGROUND: Case-control studies suggested a moderate, but consistent, association of hepatitis C virus (HCV) infection with lymphoid tissue malignancies, especially non-Hodgkin lymphoma (NHL). More limited data suggested that hepatitis B virus (HBV) infection might also be associated with NHL. However, prospective studies on the topic are few. METHODS: A nested case-control study was conducted in eight countries participating in the EPIC prospective study. Seven hundred thirty-nine incident cases of NHL, 238 multiple myeloma (MM), and 46 Hodgkin lymphoma (HL) were matched with 2,028 controls. Seropositivity to anti-HCV, anti-HBc, and HBsAg was evaluated and conditional logistic regression was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (CI) for NHL, MM, or HL, and their combination. RESULTS: Anti-HCV seropositivity among controls in different countries ranged from 0% to 5.3%; HBsAg from 0% to 2.7%; and anti-HBc from 1.9% to 45.9%. Similar nonsignificant associations were found with seropositivity to HBsAg for NHL (OR = 1.78; 95% CI: 0.78-4.04), MM (OR = 4.00; 95% CI: 1.00-16.0), and HL (OR = 2.00; 95% CI: 0.13-32.0). The association between HBsAg and the combination of NHL, MM, and HL (OR = 2.21; 95% CI: 1.12-4.33) was similar for cancer diagnosed less than 3 and 3 or more years after blood collection. No significant association was found between anti-HCV and NHL, MM, or HL risk, but the corresponding CIs were very broad. CONCLUSIONS: Chronic HBV infection may increase the risk of lymphoid malignancies among healthy European volunteers. IMPACT: Treatment directed at control of HBV infection should be evaluated in HBsAg-seropositive patients with lymphoid tissue malignancies.

The role of MYH gene in genetic predisposition to colorectal cancer: another piece of the puzzle.

Biallelic germline mutations in the MYH gene cause MYH-Associated Polyposis but patients with a single mutation possibly have an increased colorectal cancer (CRC) risk. Using DNA from consecutive CRC patients we carried out a case-control study, with the aim to contribute data on the Italian population. Genotyping of four MYH mutations found two biallelic and two monoallelic carriers among 439 cases, and only one heterozygous individual among 247 age-matched controls. The frequencies of the mutant alleles were 0.68% (6/878) and 0.20% (1/494), respectively. These differences were not statistically significant. Results on the monoallelic carriers were combined with those from 11 studies on other populations, and the risk of developing a CRC was estimated with an OR=1.11 (95% CI=0.90; 1.36), yet not reaching a significant evidence of increased CRC risk.