Increased Incidence of Cancer Observed in HIV/hepatitis C Virus-Coinfected Patients Versus HIV-Monoinfected

Héctor Meijide; Sonia Pértega; Iria Rodríguez-Osorio; Ángeles Castro-Iglesias; Josefa Baliñas; Guillermo Rodríguez-Martínez; Álvaro Mena; Eva Poveda

Disclosures

AIDS. 2017;31(8):1099-1107. 

In This Article

Results

A total of 2318 patients were included in the cohort, of which, 1461 (63.0%) were HIV-monoinfected patients and 857 (37.0%) were HIV/HCV-coinfected. The prevalence of chronic HBV infection was 2.6% in the first group and 6.4% in the second. One hundred and forty-nine (17.4%) coinfected patients received anti-HCV therapy (all with interferon based regimens); of these, 71 (47.6%) achieved sustained viral response. The main characteristics of the cohort population are shown in Table 1.

Cancer Incidence Rate and Comparison With General Population

In the study, the number of person-years at risk was 27 086, with an average of 11.7 ± 7.4 years per patient. A total of 185 patients (117 HIV-monoinfected and 68 HIV/HCV-coinfected) had at least one malignancy during follow-up, with an overall incidence rate of 696.0 cases per 100 000 person-years of follow-up (829.1 in HIV-monoinfected patients and 545.4 in HIV/HCV-coinfected patients). Crude incidence rates for ADC and NADC in HIV-monoinfected patients and HIV-HCV-coinfected patients are presented in Table 2.

After computing age-standardized rates, a statistically significant increased incidence rate was observed for all types of cancer when compared with the incidence in general population (SIR = 3.8; 95% CI: 3.3–4.4). HIV/HCV-coinfected patients, in comparison to HIV-monoinfected, showed a higher SIR for NADC and a lower SIR for ADC (Table 2). For all age groups, a higher cancer incidence was observed in comparison to the general population, reaching statistically significance for groups between 18 and 64 years (Fig. 1). Monoinfected HIV patients showed higher incidence rates for groups between 18 and 44 years, whereas HIV/HVC-coinfected patients showed higher incidence for ages between 45 and 64 years. The 5.13% of HIV-monoinfected and 0.58% of HIV/HCV-coinfected patients of the cohort was older than 64 years (at the end of follow-up or cancer diagnosis); eight cancers were found in this age group (all in monoinfected) (Fig. 1).

Figure 1.

Age-specific incidence rates of cancer in HIV-monoinfected and HIV/hepatitis C virus (HCV)-coinfected patients, comparatively with that in the general population (GLOBOCAN 2012).

The study period has been divided into two (1993–2003 and 2004–2014) and the crude incidence of ADC and NADC is shown in Table 2. The crude incidence of ADC in HIV-monoinfected patients was much higher during the first period (682.6 cases per 100 000 person-years) than in the second (282.3 cases per 100 000 person-years). Conversely, the incidence in coinfected patients was lower during the first period than in the second (61.2 versus 196.1 cases per 100 000 person-years).

At HIV diagnosis, patients with NADC were older (36.6 ± 11.7 years) than those with ADC (35.3 ± 13.1 years) and those without cancer (31.9 ± 9.7), P < 0.001. At cancer diagnosis, patients with NADC were also older (47.8 ± 10.4 years) than those with ADC (40.0 ± 11.9 years), P < 0.001.

Cancer Location

The description of the location of all cancers is included in Table S1, http://links.lww.com/QAD/B57. The NHL was the most common cancer (26.5%), the majority of them (90.2%) were B-cell high-grade lymphomas. Comparatively with the general population the SIR of NHL in HIV-monoinfected patients was SIR = 19.1 (95% CI: 12.1–40.7) and in HIV/HCV-coinfected patients was SIR = 12.2 (6.1–20.7). The 82.9% of NHL in HIV-monoinfected were diagnosed between 1993 and 2003, whereas in the coinfected group most of the NHL was diagnosed between 2004 and 2014 (78.6%). The NHL was diagnosed 0.5 years (0–2.6) after HIV diagnosis in monoinfected patients and 7.8 years (2.1–10.4) in coinfected patients, P < 0.001. The time of ART exposure was also much shorter in monoinfected than in coinfected patients [1.0 years (0–2.4) versus 6.2 (2.4–8.2), P < 0.001]. The incidence of Hodgkin lymphoma (HL) was higher than for the general population in monoinfected patients (SIR = 16.1; 95% CI: 5.0–51.3) and in coinfected patients (SIR = 21.7; 6.7–67.9).

Lung cancer (LC) is the most incident NADC. The main histological type of LC was adenocarcinoma (60.0% of the cases) and most LC was diagnosed in advanced stages (78.0% in stage III or IV). The incidence was higher than in the general population for both groups: HIV-monoinfected patients (SIR = 4.2; 2.8–6.5) and HIV/HCV-coinfected patients (SIR = 4.1; 2.7–6.3). All HCC (18 cases) appeared in HIV/HCV-coinfected patients, with the majority of being cirrhotic (94.4%). The SIR in coinfected was SIR = 24.0 (10.6–54.3).

Cumulative Incidence of Cancer in the Follow-up

Figure 2 shows the cumulative incidence of ADCs and NADCs at different time points in the follow-up after HIV diagnosis. Globally, the cumulative incidence of cancer reached 3.5% (95% CI: 2.7–4.2%) at 5 years after HIV diagnosis and 6.4% (5.4–7.4%) at 10 years. The probability for a PLWH of being alive and cancer-free at the same time points was 88.8% and 79.3%, respectively. The 10 and 20 years cumulative incidence of ADC was 3.8% and 4.3% in monoinfected patients and 1.1% and 1.7% in coinfected patients. On the contrary, the cumulative incidence of NADC was 2.3% (10 years) and 3.6% (20 years) in monoinfected, in coinfected patients was 1.9% and 4.8%, respectively.

Figure 2.

Competing risk analysis of AIDS-defining and non AIDS-defining cancer incidence in the follow-up after diagnosis of HIV patients.

During the follow-up, ADCs were less frequent in HIV/HCV-coinfected patients than in HIV-monoinfected patients. On the contrary, no differences were observed in the incidence rate of NADC between coinfected and monoinfected patients. However, after adjusting for age at HIV diagnosis, sex and transmission route, a higher cumulative incidence of NADC was observed for HIV/HCV-coinfected patients when compared with HIV-monoinfected patients (adjusted SHR = 1.80; 95% CI: 1.15–2.81). After excluding the HCC, the cumulative incidence of NADC remains higher in coinfected patients (adjusted SHR = 1.26; 1.02–1.94) (Table 3).

Cancer prognosis

Seven (3.8%) patients developed a second neoplasia; five of them had ADCs as their first cancer [four Kaposi's sarcoma (KS) and one NHL] and two NADCs (HL and prostate). Regarding the second tumor, six of seven were NADCs and the median time from the first to the second malignancy was 6.0 years (3.2–12.5).

In the mortality analysis, 124 patients (64.6% of patients with ADC and 68.9% with NADC) died after cancer diagnosis, with a median survival of 6 months (0–14). One-year mortality was 39.2% in ADCs (95% CI: 28.8–50.1) and 53.8% in NADCs (44.3–63.0), with an odds ratio = 1.8 (1.0–3.3) and P = 0.055. The comparison of mortality between HIV-mono and HIV/HCV-coinfected patients is shown in Table 1.

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