Changing cancer prognosis among people with HIV over two decades: Trends in mortality and net survival in Milan, Italy

BACKGROUND: Cancer is a major cause of morbidity and mortality among people with HIV (PWH). We assessed temporal trends in five-year mortality and compared recent cancer survival with standardized Italian general-population estimates. METHODS: We conducted a retrospective single-center cohort study including adult PWH diagnosed with malignancy at Luigi Sacco Hospital, Milan, between 2000 and 2020. Cancers were classified as AIDS-defining cancers (ADCs), virus-related non-AIDS-defining cancers (NADCs), and non-virus-related NADCs. Five-year all-cause and cancer-related mortality were compared between 2000-2007 and 2008-2020 using survival estimates and adjusted Cox models. For selected cancers diagnosed in 2008-2020, five-year net survival was estimated using the Ederer II method and descriptively compared with standardized Italian estimates. RESULTS: Overall, 476 malignancies were diagnosed, including 200 ADCs and 276 NADCs. Five-year all-cause mortality decreased from 39.3% to 15.7% for ADCs (adjusted hazard ratio [aHR] 0.39, 95% confidence interval [CI] 0.20-0.74; p = 0.004), from 56.4% to 31.1% for virus-related NADCs (aHR 0.34, 95% CI 0.16-0.71; p = 0.004), and from 58.8% to 44.3% for non-virus-related NADCs (aHR 0.55, 95% CI 0.32-0.94; p = 0.029). Five-year net survival in PWH was 30% for lung cancer, 60% for liver cancer, 83% for anal cancer, 71% for non-Hodgkin lymphoma, and 95% for Kaposi sarcoma. Corresponding standardized general-population estimates were 24%, 31%, 70%, 80%, and 84%, respectively. CONCLUSIONS: Five-year mortality among PWH with cancer improved substantially over time, particularly for ADCs and virus-related NADCs. Net survival point estimates were numerically higher than standardized references for liver and anal cancer, broadly similar for lung cancer, and lower for non-Hodgkin lymphoma; the Kaposi sarcoma reference was historical (2005-2009). Persistently high mortality among PWH with non-virus-related cancers underscores the need to strengthen prevention, early diagnosis, and access to appropriate oncological care.