Is human herpesvirus 8 infection more common in men than in women? Systematic review and meta-analysis

Abstract

All forms of Kaposi sarcoma (KS) are more common in men than in women. It is unknown if this is due to a higher prevalence of human herpesvirus 8 (HHV-8), the underlying cause of KS, in men compared to women. We did a systematic review and meta-analysis to examine the association between HHV-8 seropositivity and gender in the general population. Studies in selected populations like for example, blood donors, hospital patients, and men who have sex with men were excluded. We searched Medline and Embase from January 1994 to February 2015. We included observational studies that recruited participants from the general population and reported HHV-8 seroprevalence for men and women or boys and girls. We used random-effects meta-analysis to pool odds ratios (OR) of the association between HHV-8 and gender. We used meta-regression to identify effect modifiers, including age, geographical region and type of HHV-8 antibody test. We included 22 studies, with 36,175 participants. Men from sub-Saharan Africa (SSA) (OR 1.21, 95% confidence interval [CI] 1.09–1.34), but not men from elsewhere (OR 0.94, 95% CI 0.83–1.06), were more likely to be HHV-8 seropositive than women (p value for interaction=0.010). There was no difference in HHV-8 seroprevalence between boys and girls from SSA (OR 0.90, 95% CI 0.72–1.13). The type of HHV-8 assay did not affect the overall results. A higher HHV-8 seroprevalence in men than women in SSA may partially explain why men have higher KS risk in this region.

Background

All forms of Kaposi sarcoma (KS) are more common in men than in women; in children the male predominance is less pronounced.^1–4 Several direct and indirect mechanisms have been suggested to explain the male predominance in KS. Sex hormones may impact KS tumorigenesis although hormone receptors were not found in KS tissue.⁵ Gender differences in the susceptibility and immunological control of human herpes virus 8 (HHV-8),^6,7 a necessary but not sufficient infectious cause of KS, may also contribute to the higher risk of developing KS in men compared to women. A correlation between higher HHV-8 seroprevalence and increased KS risk has been shown in men who have sex with men (MSM).⁸ However, in heterosexual people it is not clear whether HHV-8 seroprevalence is higher in men than in women and could therefore explain the observed male predominance in KS risk, particularly among adults. Several studies have reported HHV-8 seroprevalence in men and women and boys and girls in different regions of the world. However, few studies were designed to specifically assess the association between gender and HHV-8 seropositivity and their findings have been conflicting.^9,10

We did a systematic literature review and meta-analysis to examine whether HHV-8 seroprevalence is higher in men than in women. Understanding gender disparities is essential to ultimately develop public health interventions to reduce HHV-8 and KS incidence. We estimated the association between HHV-8 seropositivity and gender in children and adults from the general population, and examined reasons for heterogeneous results between studies.

Methods

Eligibility criteria

We included HHV-8 seroepidemiological studies that recruited participants from a general population in any region of the world. HHV-8 seropositivity was used as a surrogate marker of current or past infection. We defined a general population as a representative sample of a population residing in a well-defined geographical region. Thus, studies done in blood donors, hospital-based studies or studies in selected populations like MSM, patients with solid organ transplantation, HIV-positive individuals, persons who inject drugs, and prisoners were excluded. We included children in developing countries who were enrolled during vaccination programs because such programs are offered routinely to the general population.¹¹ We included studies that reported data on HHV-8 seroprevalence for men and women or boys and girls; or odds ratios (ORs) of the association between gender and HHV-8 seroprevalence; irrespective of whether this was the main outcome of the study or not. Studies which did not report HHV-8 data separately for children and adults were excluded. For publications that included both children and adults, we treated the results for children and adults as separate studies. If a study population included more than 80% adults (arbitrary cut-off), we considered it as an adult population study. For each study we used the age cut-off for differentiation between childhood and adulthood as defined in the respective publication. We included studies that gave male and female study participants the same type of HHV-8 test (e.g. enzyme immunoassay [EIA], immunofluorescent assay [IFA]) and antigens (e.g. ORF73, K8.1).

Literature search

We searched MEDLINE and EMBASE, without language restrictions, for published reports from 01/1994 to 02/2015 using an electronic search strategy previously described by Rohner et al¹². We screened reference lists of relevant reviews, and searched the internet for additional material. We examined abstracts from the following conferences: the annual meeting of the American Society of Clinical Oncology (ASCO), the Conference on Retroviruses and Opportunistic Infections (CROI) and the International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies (ICMAOI) since 2008. We screened titles and abstracts of all retrieved references, and reviewed the full-text of potentially eligible articles. We only excluded articles based on titles and abstracts if the studies were either clearly done in selected, non-eligible populations or if HHV-8 seroprevalence was not measured at all. For all other studies the full texts including tables and figures were reviewed to assess eligibility. Four reviewers (ER, NW, ZH, LB) assessed whether the identified articles reported data on HHV-8 seroprevalence and thereafter two reviewers (LB, ER) assessed eligibility specifically for the current systematic review. In studies where the primary reviewers did not agree, they consulted an additional reviewer (JB).

Data extraction

Two reviewers (LB, ER) extracted data from the articles using a standardized form. The extracted data included the study objectives, design, and sampling strategy. Participant characteristics such as age, socio-economic status, sexual activity, HIV status and co-infections, when reported, were collected. We also recorded the type of tests (EIA, IFA) and antigens (latent, lytic) used to detect antibodies against HHV-8. We recorded outcome data on HHV-8 seroprevalence separately for male and female study participants, as well as the unadjusted and adjusted ORs of the association between HHV-8 seropositivity and gender, and the potential confounders for which the authors had adjusted. Two reviewers (LB, ER) entered the extracted data in duplicate into an electronic database (Epidata version 3.1, The EpiData Association, Odense, Denmark).

Statistical analyses

We used random-effects models to combine unadjusted ORs of the association between gender and HHV-8 seropositivity. For studies that did not report an OR, we calculated unadjusted ORs based on extracted HHV-8 seroprevalence data. If studies used different HHV-8 testing strategies, we chose EIA over IFA and lytic antigens over latent antigens, combined tests over a single test, and algorithms where only one test had to be positive over algorithms where all tests had to be positive. We assessed between-study heterogeneity using I²-statistics.¹³ We stratified main analyses by region and age and used univariable and bivariable meta-regression analyses to explore sources of between-study heterogeneity.¹⁴ We considered the following variables: age (children, adults); geographical region (sub-Saharan Africa (SSA), other regions); ethnicity (>80% Black, >80% Asian (arbitrary cut-offs), various ethnicities/unclear); country income level, as defined by the World Bank (low, middle, high income level);¹⁵ country level HIV prevalence (<5%, 5–15%, >15%);^16,17 study site (rural, urban); HHV-8 test (EIA, IFA) and antigen (lytic, latent); and, study size (number of study participants: < 500, 500–999, 1,000–1,999, ≥ 2,000). For studies conducted in SSA we assumed that participants were mainly black, if not otherwise stated. In sensitivity analyses we used fixed-effects instead of random-effects meta-analysis; excluded studies for which the number of analyzed male and female participants was not reported; chose outcomes based on latent antigens over lytic antigens, and outcomes based on IFA over EIA. Where available, we also compared adjusted and unadjusted study results and performed analyses using adjusted ORs. We did all analyses in Stata version 13.1 (StataCorp LP, College Station, TX, USA).

Results

Selection of studies

We identified 4,140 references through the database searches, including 3,037 unique references. We excluded 1,686 irrelevant references based on titles and abstracts, and assessed the full texts of the remaining 1,351 articles. After full text assessment, 1,331 references were excluded (see Appendix Figure 1). Common reasons for excluding references were that studies were not done in general populations (304 references), that references were reviews, book chapters and editorials rather than original research (291 references), that examinations were done in samples other than blood (189 references), and that HHV-8 seroprevalence was not reported separately by gender (157 references). Three additional studies were excluded because they did not report HHV-8 seroprevalence data for children and adults separately.^18–20 Thus, 17 publications reporting a total of 22 relevant studies in 36,175 children and adults were included.^21–37

Characteristics of included studies

Studies were done in ten different countries: Cameroon, South Africa, Tanzania, Uganda, Egypt, China, French Guiana, USA, Italy, and Sweden, see Table 1. The median number of participants per study was 706 (interquartile range [IQR] 427–1,477). Nine (41%) studies were conducted in children, and 13 (59%) in adults. Age cut-offs for differentiation between childhood and adulthood varied between studies and ranged from 14 to 19 years. Thirteen (59%) studies mainly included black participants, two (9%) studies mainly included Asian participants, and seven (32%) studies were done in populations with various or unclear ethnicities. The primary objectives of the included studies were to study HHV-8 seroprevalence (16 studies), risk factors for HHV-8 infection (12 studies), and HHV-8 transmission (7 studies). In nine studies (41%), blood samples were collected specifically for the HHV-8 study whereas in 13 (59%) the samples were originally collected for other purposes. Thirteen studies (59%) used EIA only; seven (32%) used IFA only; one study used IFA and Western Blot (WB); and one study used both EIA and IFA. Fourteen studies (64%) tested for lytic antigens only, and eight (36%) tested for latent and lytic antigens. One study from Uganda³⁷ and one study from the USA²⁶ reported data on the proportion of included MSM. In these two studies the proportion of MSM in men was <2%. Nine studies (41%) reported HIV prevalence in their study population, and HIV prevalence ranged between 0 and 39%. Adjusted ORs were reported for seven studies (32%). Studies adjusted for different factors, including age, residence, ethnicity, marital status, and education (Table 1).

Table 1.

Characteristics of included studies

Author year	Country	Study period	HHV-8 test and antigen used	Sample size	HIV+ (%)	MSM in men (%)	HHV-8 seroprevalence (%)		Odds ratio (95% confidence interval)ǂ
							males	females	Unadjusted	Adjusted
Sub Saharan Africa, adults
Biryahwaho 2010	Uganda	2004–2005	EIA lytic	2681	5.7	NR	57.5**	53.7**	NR	1.22 (1.03–1.45) 1
Butler 2011*	Uganda	2002	EIA lytic	1477	6.3	NR	42.9	37.6	1.3 (1.02–1.5)	1.3 (1.02–1.6) 2
Malope 2008	South Africa	2001	EIA latent & lytic	1146	38.8	NR	47.5	46.0	1.1 (0.8–1.4)	NR
Mbulaiteye 2003*	Tanzania	1985	EIA lytic	361	NR	NR	88.4	79.0	NR	NR
Plancoulaine 2004*	Cameroon	1998-NR	IFA lytic	299	NR	NR	78.4†	72.1†	NR	NR
Wawer 2001	Uganda	1994–1995	IFA & WB, latent & lytic	522	14.6	<0.5	42.7	35.0	1.38 (1.0–2.0)	1.33 (0.88–2.02) 3
Sub-Saharan Africa, children
Butler 2009	South Africa	2003	EIA & IFA lytic	427	6.4	NA	NR	NR	0.45 (0.18–1.1)	0.44 (0.18–1.1) 4
Butler 2011*	Uganda	2002	EIA lytic	1382	<1	NA	27.3	26.6	1.04 (0.82–1.3)	1.00 (0.79–1.3) 2
Dedicoat 2004	South Africa	2000–2002	EIA lytic	2497	6.2	NA	10	13	NR	NR
Mbulaiteye 2003*	Tanzania	1985	EIA lytic	437	NR	NA	58.7	54.5	1.18 (0.7–2.0)	1.1 (0.5 – 2.5) 5
Plancoulaine 2004*	Cameroon	1998-NR	IFA lytic	309	NR	NA	43.8†	46.8†	NR	NR
Outside Sub-Saharan Africa, adults
Engels 2007	USA	1988–1994	EIA lytic	13894	NR	1.1	1.6**	1.6**	NR	NR
Fu 2009	China	2007	EIA latent & lytic	2228	NR	NR	18.3	20.0	0.88 (0.71–1.09)	NR
Mbulaiteye 2008*	Egypt	1992	EIA lytic	730	NR	NR	22.1	25.3	NR	NR
Plancoulaine 2000*	French Guiana	1994–1998	IFA latent & lytic	681	0	NR	18.8†	19.1†	NR	NR
Serraino 2003	Italy	1998-NR	IFA lytic	200	NR	NR	9.0	6.0	NR	NR
Tedeschi 2006	Sweden	1998–1999	IFA lytic	520	NR	NR	15.0†	13.8†	NR	NR
Wang 2011	China	NR	EIA latent & lytic	1008	NR	NR	22.3	23.8	0.91 (0.68–1.23)	NR
Outside Sub-Saharan Africa, children
Anderson 2008	USA	1988–1994	EIA latent & lytic	4166	NR	NA	1.2**	1.6**	0.7 (0.3–1.7)	NR
Mbulaiteye 2008*	Egypt	1992	EIA lytic	235	NR	NA	9	20	0.4 (0.2–0.9)	0.4 (0.2–0.8) 6
Perna 2000	Italy	1995–1997	IFA latent & lytic	319	0	NA	5.4	7.3	NR	NR
Plancoulaine 2000*	French Guiana	1994–1998	IFA latent & lytic	656	NR	NA	6.5†	8.2†	NR	NR

^*Separated into children and adult studies for analyses;

^**weighted;

^†calculated;

^ǂas reported in the publication, reference group set to female for all studies.

Adjustments:

¹age, residence (urban vs rural), region, marital status, education;

²age, ethnicity, household density, water source, number of HHV8+ household members;

³age, marital status, education, occupation, sex partners, STDs;

⁴age, HIV status, study site (rural vs urban);

⁵age, HHV-8 serostatus of relatives, HHV-8 serostatus of older sibling, elevation of village,

⁶schistosomiasis

EIA, enzyme immunoassay; HHV-8, human herpesvirus 8; IFA, immunofluorescent assay; MSM, men who have sex with men; NA, not applicable; NR, not reported; STDs: sexually transmitted diseases; WB: western blot.

Main findings and meta-regression analyses

The main analysis, stratified by geographical region and age, is presented in Figure 1 and Table 2. Overall, there was no association between gender and HHV-8 seropositivity (OR 1.01, 95% CI 0.91–1.11). Heterogeneity between studies was moderate (I²=44%) but statistically significant (p=0.014). In SSA, male gender was associated with HHV-8 seropositivity in adults (OR 1.21, 95% CI 1.09–1.34) but not in children (OR 0.90, 95% CI 0.72–1.13; p-value for interaction=0.030). Outside SSA, male gender was not associated with HHV-8 seropositivity in adults (OR 0.94, 95% CI 0.83–1.06). There was some evidence for a negative association between male gender and HHV-8 seropositivity in children (OR 0.68, 95% CI 0.49–0.94) but the difference between adults and children was not statistically significant (p-value for interaction=0.098). Comparing the HHV-8/gender associations between regions (SSA versus outside SSA), the difference was statistically significant in adults (p=0.010), but not in children (p=0.189). In bivariable meta-regression the interaction of the HHV-8/gender association with age (children versus adults) and region (SSA versus outside SSA) remained statistically significant (p-values for interaction for age=0.002, for region=0.002).

Figure 1.

Association between HHV-8 seropositivity and gender in children and adults from sub-Saharan Africa and other regions. The blocks and horizontal lines represent the odds ratios (OR) of the association between HHV-8 seropositivity and gender with their 95% confidence intervals (CI) for each study. The center of the diamonds is the pooled point estimate of the studies included in each population group, and the width of the diamonds represents the 95% CI of the pooled OR. P: p-value from meta-regression analysis.

Table 2.

Association between HHV-8 seropositivity and gender (male versus female), stratified analyses

	Age						Region
	Adults		Children			P	SSA		Outside SSA			P
	N	OR (95% CI)	P	N	OR (95% CI)		N	OR (95% CI)	P	N	OR (95% CI)
Overall	13	1.09 (0.98–1.20)		9	0.84 (0.70–1.01)		11	1.10 (0.96–1.27)		11	0.90 (0.80–1.01)
Region
Sub-Saharan Africa	6	1.21 (1.09–1.34)	0.010	5	0.90 (0.72–1.13)	0.189		-			-
Outside SSA	7	0.94 (0.83–1.06)		4	0.68 (0.49–0.94)			-			-
Age
Adults		-			-		6	1.21 (1.09–1.34)	0.030	7	0.94 (0.83–1.06)	0.098
Children		-			-		5	0.90 (0.72–1.13)		4	0.68 (0.49–0.94)
Ethnicity
> 80% Black	7	1.19 (1.08–1.32)	0.027	6	0.89 (0.73–1.09)	-	11	1.10 (0.96–1.27)	-	2	0.91 (0.66–1.26)	0.938
> 80% Asian	2	0.90 (0.76–1.07)		0	-		0	-		2	0.90 (0.76–1.07)
Various ethnicities/unclear*	4	0.98 (0.81–1.19)		3	0.63 (0.43–0.94)		0	-		7	0.89 (0.73–1.08)
Country income level
Low	4	1.25 (1.10–1.43)	0.040	2	1.08 (0.88–1.32)	0.079	6	1.20 (1.08–1.33)	0.050	0	-	0.427
Middle	5	0.96 (0.84–1.09)		4	0.71 (0.54–0.92)		5	0.91 (0.70–1.18)		4	0.86 (0.72–1.02)
High	4	1.02 (0.84–1.25)		3	0.75 (0.52–1.07)		0	-		7	0.95 (0.80–1.13)
Country HIV prevalence
< 5%	8	0.96 (0.85–1.08)	0.038	5	0.74 (0.57–0.97)	0.079	2	1.09 (0.70–1.70)	0.118	11	0.90 (0.80–1.01)	-
5–15%	4	1.25 (1.10–1.43)		2	1.08 (0.88–1.32)		6	1.20 (1.08–1.33)		0	-
> 15%	1	1.06 (0.83–1.35)		2	0.70 (0.51–0.98)		3	0.82 (0.58–1.17)		0	-
Study site
Rural	7	1.15 (0.95–1.38)	0.757	6	0.88 (0.71–1.09)	0.727	8	1.13 (0.93–1.37)	0.816	5	0.86 (0.72–1.03)	0.727
Urban	1	1.06 (0.83–1.35)		1	0.72 (0.29–1.79)		1	1.06 (0.83–1.35)		1	0.72 (0.29–1.79)
Mixed rural/urban*	5	1.05 (0.92–1.19)		2	0.65 (0.41–1.02)		2	0.81 (0.33–2.00)		5	0.94 (0.81–1.09)
Test used for HHV-8 detection
EIA	10	1.07 (0.95–1.19)	0.501	7	0.86 (0.71–1.05)	0.470	9	1.10 (0.95–1.26)	0.211	8	0.89 (0.79–1.00)	0.426
IFA	2	1.17 (0.75–1.82)		1	0.72 (0.29–1.79)		0	-		3	1.06 (0.71–1.58)
EIA and IFA	0	-		1	0.45 (0.18–1.11)		1	0.45 (0.18–1.11)		0	-
IFA and WB	1	1.38 (0.97–1.97)		0	-		1	1.38 (0.97–1.97)		0	-
Antigen used for HHV-8 detection
Lytic	9	1.14 (1.02–1.28)	0.209	7	0.85 (0.68–1.05)	0.605	9	1.08 (0.91–1.28)	0.657	7	0.93 (0.78–1.10)	0.630
Latent and lytic	4	1.02 (0.86–1.21)		2	0.73 (0.46–1.15)		2	1.17 (0.91–1.51)		4	0.88 (0.75–1.03)
Number of participants
< 500	3	1.63 (1.12–2.38)	0.277	5	0.76 (0.51–1.14)	0.788	5	1.13 (0.79–1.63)	0.753	3	0.72 (0.35–1.49)	0.755
500–999	4	1.06 (0.85–1.33)		1	0.78 (0.43–1.41)		1	1.38 (0.97–1.97)		4	0.92 (0.74–1.14)
1000–1999	3	1.09 (0.92–1.30)		1	1.04 (0.82–1.32)		3	1.13 (0.99–1.28)		1	0.92 (0.68–1.23)
≥ 2000	3	1.03 (0.86–1.22)		2	0.75 (0.60–0.93)		2	0.95 (0.61–1.46)		3	0.91 (0.78–1.07)

CI, confidence interval; EIA, enzyme immunoassay; HHV-8, human herpesvirus 8; HIV, human immunodeficiency virus; IFA, immunofluorescent assay; N, number of studies; OR, odds ratio; P, p-value for interaction; SSA, Sub-Saharan Africa; WB, western blot.

^*excluded from test for interaction

There was some evidence for an interaction of the association between HHV-8 and gender with country income level and country HIV prevalence; however, the results did not show a dose-response relationship, see Table 2. Study size, type of HHV-8 test or the HHV-8 antigen tested were not related to HHV-8/gender associations. For study site and ethnicity, the number of studies included in the meta-regression was too small to allow solid conclusions. Within the four studies that reported separate results for lytic and latent antigens there was no evidence for an interaction of type of antigen tested with the association between HHV-8 and gender (lytic antigens pooled OR 0.87, 95% CI 0.71–1.06; latent antigens OR 1.08, 95% CI 0.89–1.32, p-value for interaction=0.226).

Sensitivity analyses

Results were similar when repeating analyses using fixed-effects models instead of random-effects models, and when using results based on IFA and latent antigens. Likewise, the results were similar when excluding studies for which the number of analyzed male and female participants were not reported and when using adjusted rather than unadjusted estimates (see Appendix Tables 1 and 2).

Discussion

This comprehensive systematic review and meta-analysis of the association between HHV-8 seropositivity and gender showed that men in SSA but not men from other regions were more likely to be HHV-8 seropositive than women. Interestingly, in SSA the difference between genders was evident in adults but not in children, indicating that the incidence of new HHV-8 infections may be higher in men than in women in early adulthood but not in childhood.

This systematic review and meta-analysis has several strengths. It is the first meta-analysis to explore the association between HHV-8 seropositivity and gender in children and adults from general populations in many different countries and regions. We restricted our analyses to studies that recruited participants from the general population to minimize selection and other biases associated with special populations, such as blood donors or people attending specialized clinics.

We excluded studies conducted in MSM, since they have higher HHV-8 seroprevalence than heterosexual men, and tried to assess the proportion of MSM in the included studies. Unfortunately, only two studies^26,37 reported the proportion of MSM. In these studies, the proportion of MSM was very low (<2%), but it is likely that due to stigma associated with homosexuality MSM behavior was underreported, especially in Africa.³⁸ We can therefore not exclude that MSM may have contributed to a higher HHV-8 seroprevalence in men compared to women in SSA. On the other hand, HIV infection increases the risk of HHV-8 seropositivity,³⁹ and in sub-Saharan Africa more women than men are HIV-infected.⁴⁰ Higher HIV prevalence in women could therefore counterbalance the effect of unreported MSM behavior on HHV-8 seroprevalence. Although several studies included in this meta-analysis reported HIV prevalence in their study population, only one study adjusted the OR of the HHV-8/gender association for HIV status.²³ In this study, adjustment for HIV status did not change the OR much. We found evidence that outside SSA, boys were less likely to be HHV-8 seropositive than girls. This finding might be spurious because it was based on few studies with small numbers of HHV-8 seropositive boys and girls. Also, the observed association was not statistically significantly different from adults outside SSA or children from SSA. Most studies used different tests to determine HHV-8 seropositivity. This made direct comparison of HHV-8 seroprevalence between studies difficult. However, within each study the same test was used on males and females, and therefore ORs of the association between HHV-8 seropositivity and gender as relative measures should be better comparable than HHV-8 seroprevalence. Indeed, in sensitivity analyses we found no evidence for an effect of the type of HHV-8 assay on the overall results.

We observed that in SSA HHV-8 seroprevalence in the general population was higher in men than women, but not in boys compared to girls. This is in line with the male predominance in KS incidence and prevalence in this region, which is mainly observed in adults and to a lesser extent in children.⁴ The higher HHV-8 seroprevalence in men from SSA indicates that men may be more susceptible to HHV-8 infection than women in this region. Both biological and behavioral factors might contribute to the gender difference in adults. Sex hormones influence immune cells and lead to generally stronger immune responses in women compared to men.⁴¹ Therefore, it is plausible that reduced immune control of HHV-8 in men might result in more frequent reactivation of HHV-8. A study from Uganda which showed that HHV-8 DNA was more commonly detected in men than women supports this hypothesis.⁴² However, we would have expected to observe this effect in adults from regions outside SSA as well. The positive association of HHV-8 seropositivity with male gender might also be explained by heterosexual transmission with more sexual contacts in men compared to women. Though, in one study²⁴ where the OR of the HHV-8/gender association was adjusted for number of sex partners, the adjusted and unadjusted OR were very similar. Another potential explanation is the notion that sexual transmission of HHV-8 could be – in contrast to other sexually transmitted infections - more efficient from women to men than from men to women.⁴³

In conclusion, it remains unclear why we found a positive association between male gender and HHV-8 seropositivity in adults from SSA, but not in adults from other regions. More research on the causal pathway from HHV-8 infection to KS and its association with gender is required to ultimately develop preventive measures against HHV-8 infection and subsequent KS in men and women. Standards of HHV-8 testing are needed to improve our ability to compare data from different studies. In the meantime, our data indicate that in SSA a higher HHV-8 seroprevalence in men may contribute to the higher KS risk observed in men than in women.

What’s new?

It is not clear why all forms of Kaposi sarcoma (KS) are more common in men than in women; whereas in children the male predominance is less pronounced. This systematic review and meta-analysis examined whether human herpesvirus 8 infection, a necessary but not sufficient cause of KS, was more common in men than in women. The authors found that men from sub-Saharan Africa, where HHV-8 is endemic, but not men from elsewhere, were more likely to be HHV-8 seropositive than women. There was no difference in HHV-8 seroprevalence between boys and girls from sub-Saharan Africa.

Abbreviations used

CI

confidence interval

DNA

deoxyribonucleic acid

EIA

enzyme immunoassay

ER

Eliane Rohner

HHV-8

human herpesvirus 8

HIV

human Immunodeficiency virus

IFA

immunofluorescent assay

IQR

interquartile range

JB

Julia Bohlius

LB

Lorin Begré

MSM

men who have sex with men

NA

not applicable

NR

not reported

NW

Natascha Wyss

OR

Odds ratio

PCR

polymerase chain reaction

SSA

sub-Saharan Africa

STD

sexually transmitted disease

USA

United States of America

WB

western blot

ZH

Zina Heg