Discussion
This is a comprehensive systematic assessment of HSV-2 epidemiology in
China. We included publications in Chinese and English major
bibliography databases and involved over one million study participants.
This study has added to the existing literature by providing a most
up-to-date, comprehensive picture of HSV-2 epidemiology in China,
mapping the Chinese provincial level of HSV-2 seroprevalence
differences, and investigating language bias between publications
identified from Chinese and English databases. Around 1 out of 12 people
in the general population were infected by HSV-2. Stratified by study
populations and geographic regions, we observed higher HSV-2 disease
burden among higher-risk populations such as FSW and participants from
northeastern China, calling for more preventive interventions for these
populations. By comparing the HSV-2 prevalence synthesized from Chinese
and English databases, we found a higher overall HSV-2 prevalence from
English bibliographic databases than Chinese, indicating the existence
of language bias and implying the importance of including both Chinese
and English publications in the review.
The HSV-2 seroprevalence among the general population is 7.9%
(6.9-8.8%), similar to the overall prevalence of HSV-2 in
Asia,21 lower than in Europe, Sub-Saharan Africa, and
Australia but higher than the Middle East and North Africa.8,10,12,13,30 With other regions whose prevalence was
flat8 or increasing10,11, we
observed the HSV-2 prevalence in China reduced by about 2% every five
years, which could be attributed to better STI clinic access and
improved STI education among the general population
nationwide.31,32 Stratified by sex, we observed
comparable HSV-2 prevalence between men and women. However, among other
populations, we found a higher HSV-2 seroprevalence among women than
men, especially higher-risk populations, with the seroprevalence
significantly higher among FSW than MSM (52.1% vs . 12.2%),
which revealed on the one hand, sustained HSV-2 transmission among this
population33 and on the other hand, the importance of
continuing healthcare and behavioral intervention to reduce HSV-2
infection among the populations vulnerable to HSV-2 infection.
Geographically, we found that the Northeastern region (Liaoning, Jilin,
and Heilongjiang) had the highest HSV-2 prevalence due to the high
proportion of STI clinic attendees with suspected genital herpes
symptoms and MSM living with HIV within this sample (10,202/15,904,
64.1%). Stratified by age group, we observed a steady increase of HSV-2
prevalence with age, consistent with increasing cumulative exposure risk
to the virus over the sexual life span and incurability of HSV-2. The
assessment of HSV-2 risk factors through meta-regression confirmed the
observations in synthesized seroprevalences: populations of higher
vulnerability to HSV-2 had higher HSV-2 prevalence as earlier studies
had higher HSV-2 prevalence than later studies.
We found heterogeneities in HSV-2 seroprevalence estimation and study
population composition between English and Chinese bibliographic
databases, indicating language bias. First, from the estimation
perspective, the overall HSV-2 seroprevalence was significantly higher
from English databases than Chinese databases (20.5% vs . 13.6%,
RR=1.10 (1.05-1.14)). Stratified by risk levels, although we found
comparable HSV-2 seroprevalence estimation among the general population,
the HSV-2 seroprevalence estimation was significantly higher among
higher-risk populations such as FSW and MSM/MSM in English databases.
Second, the composition of the study population significantly differed
between the publications identified from English and Chinese databases.
The sample size of general populations in publications from Chinese
databases is more than 15-fold that from English bibliography databases,
mainly attributable to the large-scale toxoplasmosis, rubella
cytomegalovirus, herpes simplex, and HIV (TORCH) screening among
pre-pregnancy and pregnancy women in clinical and community settings.
Meanwhile, the sample size of the higher-risk population in English
databases accounted for one-third of the overall identified sample size,
compared to around 3% in Chinese databases. Third, Chinese publications
were more geographically diverse, providing HSV-2 seroprevalence not
just in southern China (e.g., Guangdong and Yunnan) but around the
country. These observations might be due to several reasons. First, the
regular TORCH screening results among the general population were harder
to be published in journals published in English bibliographic databases
than in Chinese databases.34 Second, higher-risk
populations had higher HSV-2 vulnerabilities and potentially higher
public health significance.35 Investigators promoted
their results in journals published in English databases for wider
attention and higher citation.36 Interestingly, on the
other hand, we found lower HSV-2 prevalence estimation among
intermediate-risk populations and drug users. The sample sizes and
numbers of the study were much lower than those of higher-risk
populations, which indicates an unmet study need for these populations.
These observations indicate a potential existence of language bias by
only including publications published in English bibliography databases
in the review. Considering the huge quantity and varying quality, most
Chinese journals have yet to be published in English bibliographic
databases.37 The synthesized results might be
distorted by restricting publications to English-language only in
literature searching.38 Previous studies have shown
that positive results in randomized controlled trials are more likely to
be published and published in English bibliographic databases,
potentially leading to overestimating the drugs’ effectiveness. The
Cochrane Handbook for Systematic Reviews and the United States Institute
of Medicine Guidelines for Systematic Reviews recommends including
non-English-language literature published in English bibliographic
databases in the review.17,39 Our study revealed that
this might not be enough to eliminate the language bias if not including
non-English bibliographic databases in the review. As a result, it could
y lead to misinterpretation of the disease’s unmet needs and a
suboptimal distribution of public health resources in HSV-2 prevention
across different populations.
There are some limitations to be noted. First, we should have included
all Chinese bibliographic databases in the literature search scope.
There are other databases, such as Weipu Database. However, we have
included the two most popular Chinese bibliographic databases in this
review and have yet to observe differences regarding the impact of
journals published in different Chinese databases. Thus, the potential
publication bias of excluding other Chinese databases is minimal.
Second, due to heterogeneities in variable categorization (such as age
group), some studies’ subgroups cannot be extracted and are categorized
into the mixed group or other populations. These studies’ information
was not fully utilized. However, the synthesized results did not differ
significantly from the categorized groups’ results. The overall
estimation should be robust to these heterogeneities in variable
categorization. Third, the current included studies, 29.4% of them had
high ROB in both quality domains, and only 4.0% of the studies had low
ROB in both domains, which implies a space for future studies to employ
probability-based sampling methods to improve study quality. Fourth, we
only presented the synthesized results for studies across different
regions. However, there were heterogeneities regarding the study
population. For example, in some regions, we identified more studies
among higher-risk populations than in other regions, which could inflate
the HSV-2, which calls for caution in interpreting the current results
prevalence in this region.