Survival after the diagnosis of de novo malignancy in liver transplant recipients.

In the setting of liver transplant (LT), the survival after the diagnosis of de novo malignancies (DNMs) has been poorly investigated. In this study, we assessed the impact of DNMs on survival of LT recipients as compared to corresponding LT recipients without DNM. A nested case-control study was conducted in a cohort of 2,818 LT recipients enrolled in nine Italian centres between 1985 and 2014. Cases were 244 LT recipients who developed DNMs after LT. For each case, two controls matched for gender, age, and year at transplant were selected by incidence density sampling among cohort members without DNM. The survival probabilities were estimated using the Kaplan-Meier method. Hazard ratios (HRs) of death and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. The all-cancer 10-year survival was 43% in cases versus 70% in controls (HR = 4.66; 95% CI: 3.17-6.85). Survival was impaired in cases for all the most frequent cancer types, including lung (HR = 37.13; 95% CI: 4.98-276.74), non-Hodgkin lymphoma (HR = 6.57; 95% CI: 2.15-20.01), head and neck (HR = 4.65; 95% CI: 1.81-11.95), and colon-rectum (HR = 3.61; 95% CI: 1.08-12.07). The survival gap was observed for both early and late mortality, although the effect was more pronounced in the first year after cancer diagnosis. No significant differences in survival emerged for Kaposi's sarcoma and nonmelanoma skin cancers. The survival gap herein quantified included a broad range of malignancies following LT and prompts close monitoring during the post-transplant follow-up to ensure early cancer diagnosis and to improve survival.

Risk of virus and non-virus related malignancies following immunosuppression in a cohort of liver transplant recipients. Italy, 1985-2014.

This cohort study assessed, in Italy, the overall pattern of risk of de novo malignancies following liver transplantation (LT). The study group included 2,832 individuals who underwent LT between 1985 and 2014 in nine centers all over Italy. Person-years (PYs) at cancer risk were computed from 30 days after LT to the date of cancer diagnosis, to the date of death or to the end of follow-up. Excess cancer risk, as compared to the general population, was estimated using standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). During 18,642 PYs, 246 LT recipients developed 266 de novo malignancies, corresponding to a 1.8-fold higher cancer risk (95% CI: 1.6-2.0). SIRs were particularly elevated for virus-related malignancies, including Kaposi's sarcoma (SIR = 53.6, 95% CI: 30.0-88.5), non-Hodgkin lymphomas (SIR = 7.1, 95% CI: 4.8-10.1) and cervix uteri (SIR = 5.4, 95% CI: 1.1-15.8). Among virus-unrelated malignancies, elevated risks emerged for head and neck (SIR = 4.4, 95% CI: 3.1-6.2), esophagus (SIR = 6.7, 95% CI: 2.9-13.3) and adrenal gland (SIR = 22.9, 95% CI: 2.8-82.7). Borderline statistically significant elevated risks were found for lung cancer (SIR = 1.4, 95% CI: 1.0-2.1) and skin melanoma (SIR = 2.6, 95% CI: 1.0-5.3). A reduced risk emerged for prostate cancer (SIR = 0.1, 95% CI: 0.0-0.5). These findings underline the need of preventive interventions and early detection of malignancies, specifically tailored to LT recipients.

Frequency and multiplicity of human papillomavirus infection in HIV-1 positive women in Italy.

BACKGROUND: Natural history of HPV infection is altered in HIV positive women, with increased risk of cervical dysplasia. Limited data are available about the influence of HPV genotypes and HPV multiple infections on cervical disease in HIV positive women. OBJECTIVES: We determined HPV genotype prevalence in cervical samples from 553 HIV-infected women attending the gynaecological service at "L. Spallanzani" Hospital. Association of HPV multiple infections with cervical abnormalities was investigated. STUDY DESIGN: MY09/MY11 consensus primers were used to detect HPV-DNA; HPV typing was performed by RFLP. A commercial array based kit was used to define unresolved RFLP patterns. RESULTS: HPV was detected in 244/553 (44.1%) patients, correlating with low CD4 counts (p<0.001) and age (p=0.001). Multiple HPV types were observed in 44.4% of cases, more frequently involving HR than LR HPV (OR=12.8, p<0.00001). Multiple HPV infections were associated with low CD4 counts (OR=3.8 in CD4<200 vs CD4≥500 cells/mm(3)). Dyskaryosis was associated with decreased CD4 counts (≥500 vs 200-499 vs <200 cells/mm(3), χ(2) for trend, p=0.001) and with HPV types multiplicity (1 vs 2-3 vs ≥4, χ(2) for trend, p<0.00001). Notably, in 3 H-SIL cases only LR types were detected (HPV62, n=2; HPV81, n=1). CONCLUSIONS: Multiple HPV infections, often involving HR types, are frequent in HIV-infected women. Association between multiple HPV infection, low CD4 count and cytological abnormalities supports the interplay of virological and immunological factors in cervical cancer pathogenesis. Assessment of multiple HPV infections might gain importance in cervical cancer screening, particularly in patients with predisposing factors like immuno-suppression.