Research paper 529

Kaposi sarcoma incidence in Mozambique: national and regional estimates Paula Meirelesa,b, Gabriela Albuquerquea,b, Mariana Vieiraa,b, Severiano Foiaa,b, Josefo Ferroc,d, Carla Carrilhoe,f and Nuno Luneta,b Kaposi sarcoma is expressed in four clinical variants, all associated with human herpes virus type 8 infection, namely, classic, endemic, immunosuppression-related and AIDS-related. The latter currently accounts for most of the burden of Kaposi sarcoma in sub-Saharan Africa, reflecting the frequency of HIV infection and its management. We aimed to estimate the incidence of Kaposi sarcoma in Mozambique and in its provinces. We estimated the number of incident cases of Kaposi sarcoma by adding up the expected number of endemic and AIDS-related cases. The former were estimated from the rates observed in Kyandondo, Uganda (1960–1971). The latter were computed from the number of AIDS-related deaths in each region, assuming that the ratio between the AIDS-related Kaposi sarcoma incident cases and the number of AIDS-related deaths observed in the city of Beira applies to all regions. A total of 3862 Kaposi sarcoma cases were estimated to have occurred in Mozambique in 2007, mostly AIDS-related, in the age group 25–49 years, and in provinces from South/Centre. The age-standardized incidence rates were 36.1/100 000 in men and 11.5/100 000 in women, with

Introduction Kaposi sarcoma is a malignant vascular neoplasm, characterized by the abnormal growth of blood vessels that develop into skin lesions or affect internal organs (Antman and Chang, 2000). Four clinical variants of the disease, namely, classic, endemic, immunosuppression-related and AIDS-related, have been described on the basis of the natural history, sites involved and prognosis (Fatahzadeh, 2012), all being associated with an infection with human herpes virus type 8 (HHV-8) (Cook-Mozaffari et al., 1998; Antman and Chang, 2000; Mbulaiteye et al., 2003; Mosam et al., 2010; Fatahzadeh, 2012). Although the endemic form has been common in Central and Eastern Africa since the 1950s (Antman and Chang, 2000), the AIDS epidemic led to a marked increase in the overall burden of Kaposi sarcoma in this region after the 1980s (Mbulaiteye et al., 2003; Mosam et al., 2010; Mbulaiteye et al., 2011; Fatahzadeh, 2012), and it has been classified as an AIDS-defining cancer (Mbulaiteye et al., 2011). The incidence of AIDS-related Kaposi sarcoma can be reduced markedly with highly active antiretroviral therapy (HAART) (Mosam et al., 2010; Fatahzadeh, 2012), and patients infected with the HIV who are on antiretroviral therapy (ART) are diagnosed with less severe forms of 0959-8278 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

a more than three-fold variation across provinces. We estimated a high incidence of Kaposi sarcoma in Mozambique, along with large regional differences. These results can be used to improve disease management and to sustain political decisions on health policies. European Journal of Cancer Prevention 24:529–534 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. European Journal of Cancer Prevention 2015, 24:529–534 Keywords: AIDS, HIV, incidence, Kaposi sarcoma, Mozambique EPIUnit – Institute of Public Health of the University of Porto (ISPUP), Department of Clinical Epidemiology, Predictive Medicine and Public Health, University of Porto Medical School, Porto, Portugal, cDepartment of Anatomical Pathology, Beira Central Hospital, dFaculty of Medicine, Catholic University, Beira, e Department of Pathology, Medical Faculty, Eduardo Mondlane University and f Department of Anatomical Pathology, Maputo Central Hospital, Maputo, Mozambique a

b

Correspondence to Nuno Lunet, MPH, PhD, Department of Clinical Epidemiology, Predictive Medicine and Public Health, University of Porto Medical School, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal Tel: + 351 222 513 652; fax: + 222 513 653; e-mail: [email protected] Received 5 July 2014 Accepted 30 October 2014

Kaposi sarcoma (Fatahzadeh, 2012). However, because sub-Saharan African countries have the highest prevalence of both HIV and HHV-8 and poor access to HAART (Mosam et al., 2010), Kaposi sarcoma remains a major public health concern in this region. Specifically in Mozambique, the prevalence of HHV-8 was just over 20% among patients attending public healthcare centres in 2008 (Caterino-De-Araujo et al., 2010), and the prevalence of HIV infection in a nationally representative sample evaluated in 2009 was 11.5% in the age group 15–49 years, although varying more than three-fold across provinces (INS, INE and ICF, 2010). In terms of the use of HAART, it was estimated that in 2010, less than half the nearly 600 000 adults needing ART were receiving it (Unaids, 2013), along with regional differences and poorer access to care in rural areas (Audet et al., 2010; Groh et al., 2011). The population-based Cancer Registry of Beira (ROB), the capital city of the province of Sofala, provides information on the number of incident cases of Kaposi sarcoma for a population of approximately half a million inhabitants, and national estimates are available from GLOBOCAN (Ferlay et al., 2010), but no rates are available for the different regions. Therefore, we aimed to estimate the incidence of Kaposi sarcoma in DOI: 10.1097/CEJ.0000000000000108

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530 European Journal of Cancer Prevention 2015, Vol 24 No 6

Mozambique and in its provinces using information on the incidence of Kaposi sarcoma observed in a neighbouring country and in a local regional cancer registry, and data on the AIDS-related mortality.

Methods We estimated the number of new Kaposi sarcoma cases by adding up the expected number of patients with incident endemic and AIDS-related Kaposi sarcomas (Fig. 1a) under the assumption that, currently, the overall frequency of Kaposi sarcoma is largely influenced by the frequency of HIV infection and its management. The methods, which were derived from those used previously by the GLOBOCAN project (Ferlay et al., 2010), are described in detail below. Results are presented as Kaposi sarcoma incidence per 100 000 inhabitants, age-specific and for all ages [crude and age-standardized – direct method, world standard

population (Segi, 1960)], separately for men and women, for Mozambique and each of its provinces. We also quantified the relation between the prevalence of HIV infection and the estimated incidence of Kaposi sarcoma, in the age group 15–49 years, across regions. Endemic Kaposi sarcoma incident cases

No data on endemic Kaposi sarcoma cases were available for Mozambique. Hence, its incidence was estimated assuming that the rates observed in the Kyandondo Cancer Registry in Uganda between 1960 and 1971 (Chaabna et al., 2013) are similar to the ones observed in 2007 in Mozambique. We used data from the Kyandondo Cancer Registry once this registry was used by the GLOBOCAN 2008 to estimate the endemic incidence of Kaposi sarcoma for the Eastern African countries that did not have a registry (Ferlay et al., 2010). The period of 1960–1971 was considered because this population-based cancer registry was established in 1951, but stopped

Fig. 1

(a)

(b) Estimation of endemic KS incident cases

Data sources 1Kyandondo

Endemic KS incident cases

ASI1×

Mozambique population in

20072

Registries, Uganda 1960 −1972

2National

Institute of Statistics

KS incident cases

Estimation of AIDS-related KS incidence cases

AIDS-related deaths

INCAM report, 2007

AIDS-related KS incident cases

Ratio=

Observed KS cases∗ − Endemic KS cases AIDS-related deaths

∗Cancer

Registry of Beira 2007−2009

Methods and data sources used to estimate the Kaposi sarcoma incident cases in Mozambique. (a) Summary of the estimation of Kaposi sarcoma incident cases. (b) Detailed methods used to estimate endemic and AIDS-related Kaposi sarcoma cases and data sources. ASI, age-standardized incidence; INCAM, Inquérito Nacional sobre Causas de Mortalidade; KS, Kaposi sarcoma.

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Kaposi sarcoma incidence in Mozambique Meireles et al. 531

functioning between 1971 and 1990 (Chaabna et al., 2013). To compute the expected number of endemic Kaposi sarcoma incident cases, we multiplied the agespecific and sex-specific incidence rates of Kaposi sarcoma in Kyandondo by the population in Mozambique in 2007 (Fig. 1b). AIDS-related Kaposi sarcoma incident cases

To estimate the sex-specific and age-specific number of AIDS-related Kaposi sarcoma incident cases, we multiplied the number of AIDS-related deaths in each province by the ratio between the AIDS-related Kaposi sarcoma incident cases in the city of Beira (the only Mozambican setting with population-based data available) and the number of AIDS-related deaths in the same setting (Fig. 1b). AIDS-related deaths

To estimate the number of AIDS-related deaths, we used data from the 2007–2008 postcensus mortality survey – Inquérito Nacional sobre Causas de Mortalidade (INCAM), referring to 2006–2007 (INE, 2009). The INCAM was developed to overcome the lack of information on mortality and its causes in Mozambique and gathers data on causes of death collected from household verbal autopsies in a nationally representative sample (INE, 2009). The provisional INCAM report provided data on the estimated total number of deaths and the percentage because of HIV/AIDS by place of residence (province or urban/rural settings) and sex or age group. As no data are available on the sex-specific and age-specific number of AIDS-related deaths in each region, we estimated it by multiplying the total number of deaths in each age group by the corresponding proportion of HIV/AIDS-related deaths, and then assumed that the proportion of the total number of HIV/AIDS-related deaths occurring in each sex was the same for all age strata. For example, in the province of Sofala, the total number of deaths in the age group 15–24 years was 1740 and the proportion of HIV/AIDS-related deaths was 40.5%, corresponding to 705 AIDS-related deaths (1740 × 0.405); the proportion of the total number of HIV/AIDS-related deaths among men was 53.8%, and therefore the number of AIDSrelated deaths among men (705 × 0.538) was 379. Ratio between the AIDS-related Kaposi sarcoma incident cases and the number of AIDS-related deaths in the city of Beira

The number of AIDS-related Kaposi sarcoma incident cases in the city of Beira was obtained by subtracting the estimated number of Kaposi sarcoma endemic cases (computed as described above) from the number of cases of Kaposi sarcoma registered by the ROB (the average number of cases in the period 2007–2009 was considered to reduce random variation) (Carrilho et al., 2013).

As the sex-specific and age-specific number of AIDSrelated deaths in the city of Beira is not provided in the INCAM report, to estimate it, we first multiplied the estimated number of deaths in the province of Sofala (calculated as described above) by the proportion of the total number of HIV/AIDS-related deaths occurring in urban settings, and then computed sex-specific and agespecific AIDS-related mortality rates in urban areas. Then, assuming that AIDS-related mortality in Beira is similar to that in the urban areas of Sofala, we calculated the expected number of AIDS-related deaths in Beira considering the population in each sex and age group in 2007. AIDS-related Kaposi sarcoma incident cases by 100 AIDS-related deaths ratios were as follows: 0–14 years, 1.2 for men, 1.0 for women; 15–24 years, 9.7 for men, 5.7 for women; 25–49 years, 11.6 for men, 5.6 for women; and more than 50 years, 5.0 for men, 1.8 for women.

Results The estimated Kaposi sarcoma incidence in Mozambique in 2007 was 27.4/100 000 in men and 9.7/100 000 in women, corresponding to an overall number of 3862 cases in the country. The proportion of AIDS-related cases was close to 100% among women and was 88% in men, ranging between 81% in Tete and 95% in Gaza (Table 1). The age groups 25–49 years and 0–14 years had the highest and the lowest age-specific incidence rates, respectively. The estimated age-specific incidence for all ages was nearly three-fold higher in men that in women in all provinces, although the male to female ratio in the age-specific estimates was closer to 1.5 in the age group 0–14 years and increased to ∼ 4.5 for ages more than 50 years. The age-standardized incidence rates in Mozambique were 36.1/100.000 for men and 11.5/100 000 for women, with a more than three-fold variation across provinces. Among men, the estimates varied from 95.1/100 000 in Gaza to 22.8/100 000 in Tete, and among women, the estimates varied from 23.0/100 000 in Gaza to 7.1/100 000 in Tete (Fig. 2). In the age group 15–49 years, there was a clear area-level association between the prevalence of HIV infection and the estimated incidence of Kaposi sarcoma across provinces (r = 0.59, P = 0.055 in men, and r = 0.86, P = 0.001 in women) (Fig. 3).

Discussion Nearly 4000 Kaposi sarcoma cases were estimated to have occurred in Mozambique in 2007, mostly AIDS-related, with higher rates in the age group 25–49 years and in the provinces from the South and Centre. The AIDS epidemic led to marked changes in the sex differences in the frequency of Kaposi sarcoma, from

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(88) (97) (100) (100) (99) 1.7 7.8 24.8 8.5 9.7 2.1 11.0 37.5 11.3 13.8 (82) (96) (100) (100) (99) 1.8 5.5 31.9 9.5 10.5 (80) (98) (100) (100) (99)

(89) (96) (100) (100) (99)

1.1 4.5 24.2 7.6 10.1

1.2 8.2 31.9 9.1 12.5

(84) (98) (100) (100) (99)

1.5 7.3 13.4 6.4 6.2

(86) (97) (100) (100) (98)

1.8 6.6 14.9 6.2 6.4

(89) (97) (100) (100) (98)

(90) (98) (100) (100) (99)

1.5 3.4 15.5 5.6 5.6

(87) (94) (100) (100) (98)

2.1 9.5 27.5 7.9 10.6

(91) (98) (100) (100) (99)

(84) (86) (90) (80) (88) 2.4 19.5 75.5 39.4 27.4 (87) (88) (91) (77) (89) 3.0 23.1 81.1 33.8 28.3 (81) (69) (84) (73) (81) 2.2 9.2 46.8 28.0 16.0 (87) (89) (93) (84) (91) 3.0 26.0 108.1 47.6 37.2 (85) (84) (85) (74) (83) 2.7 17.5 47.8 30.1 19.1 (83) (86) (84) (74) (83) 2.4 20.2 45.7 29.6 19.7 (76) (84) (91) (82) (89) 1.6 17.9 82.6 43.0 31.8 (76) (76) (90) (77) (87) 1.7 11.7 71.1 34.2 29.0 (85) (80) (92) (83) (90) 2.6 13.9 95.2 44.0 29.1 (70) (87) (93) (82) (90)

Nampula Maputo Province Maputo City Manica Inhambane Gaza Cabo Delgado Beira

Incidence of Kaposi sarcoma per 100 000 (% of AIDS-related cases) Men 0–14 3.8 (90) 1.9 (79) 4.2 (91) 1.3 15–24 26.4 (89) 21.3 (87) 34.4 (92) 22.0 25–49 106.0 (93) 60.0 (88) 218.5 (97) 101.0 > 50 59.0 (87) 50.2 (85) 89.9 (91) 42.5 All ages 44.6 (92) 26.2 (87) 65.4 (95) 30.8 Women 0–14 3.0 (93) 1.4 (86) 2.8 (93) 1.0 15–24 13.8 (99) 9.8 (98) 12.8 (98) 9.4 25–49 49.1 (100) 22.4 (100) 54.4 (100) 29.0 > 50 18.8 (100) 12.9 (100) 12.9 (100) 8.2 All ages 20.1 (99) 10.0 (99) 19.7 (99) 10.9

Table 1

Incidence of Kaposi sarcoma in Mozambique in 2007, by province and in the entire country, among men and women

Niassa

Sofala

Tete

Zambezia

Mozambique

532 European Journal of Cancer Prevention 2015, Vol 24 No 6

a male/female ratio of 20 : 1 in endemic Kaposi sarcoma to 2 : 1 in AIDS-related Kaposi sarcoma (Mosam et al., 2010; Mbulaiteye et al., 2011), which is reflected in our estimates. The estimated incidence of Kaposi sarcoma is different across provinces, with higher rates in the south and lower rates in the north, following a pattern that resembles closely the distribution of HIV prevalence in the country, which reflects distinct socioeconomic status, access to education, language, and sex relationships (Audet et al., 2010). This shows that the regional differences in Kaposi sarcoma incidence in Mozambique are mostly related to HIV infection and its management, which is in accordance with the evidence of similar seroprevalence of HHV-8 in different provinces (Caterino-De-Araujo et al., 2010). The Kaposi sarcoma age-standardized incidence rates obtained in the present analysis were higher than those estimated by the GLOBOCAN project for 2008 (36.1/100 000 vs. 22.7/100 000 in men and 11.5/100 000 vs. 9.6/100 000 in women) (IARC, 2010), especially among men. This is probably because we used local sources of data to estimate the ratio between the number of AIDSrelated cases of Kaposi sarcoma and the number of AIDS deaths, which is likely to reflect more closely the epidemiology of Kaposi sarcoma in Mozambique. The most recent GLOBOCAN estimates for 2012 are 33.0/100 000 men and 15.4/100 000 women (IARC, 2014), but direct comparisons are more difficult because of differences in the periods of analysis and methods used for estimation. Our study used the best available data in Mozambique to estimate the incidence of Kaposi sarcoma in different provinces, across which the prevalence of HIV infection and the access to ART is expected to vary considerably. This represents a step forward towards a better understanding of the burden of Kaposi sarcoma in the country and the heterogeneity of its distribution across regions, and is an example of how estimates with potential impact in public health action can be produced using all available sources of information, even when these are scarce. However, some limitations should be noted. One of the assumptions of the method used in our study is that the overall number of incident cases of Kaposi sarcoma includes a subset of endemic cases, which, currently, is expected to be similar to what was observed in neighbouring countries before the AIDS epidemic. We estimated the incidence of endemic Kaposi sarcoma using data only from one data source: the Kyandondo registry in Uganda. Although we cannot ensure that the rates in this setting apply to Mozambique and the precision of the estimates from this registry was low, which contributed to no cases being observed among the older women, the same pattern was observed in the Harare registry in Zimbabwe for the same period (Chaabna et al., 2013); nevertheless, the contribution of endemic Kaposi

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Kaposi sarcoma incidence in Mozambique Meireles et al. 533

Fig. 2 Niassa 25.1/100 000

Niassa 7.7/100 000

Cabo delgado 33.4/100 000 Tete 22.8/100 000

Cabo delgado 11.9/100 000

Tete 7.1/100 000 Nampula 24.7/100 000

Nampula 7.3/100 000

Zambezia 37.5/100 000

Manica 42.5/100 000

Manica 13.6/100 000

Zambezia 12.7/100 000

Sofala 49.5/100 000 Gaza 95.1/100 000

Sofala 16.8/100 000 Gaza 23.0/100 000

Inhambane 45.0/100 000

Inhambane 12.8/100 000 Maputo city 10.4/100 000

Maputo city 32.1/100 000 Maputo province 38.6/100 000

KS ASIR among men N

Maputo province 13.8/100 000

Kaposi sarcoma incidence in Mozambique: national and regional estimates.

Kaposi sarcoma is expressed in four clinical variants, all associated with human herpes virus type 8 infection, namely, classic, endemic, immunosuppre...
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