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. 2023 Jan 6;56:101817. doi: 10.1016/j.eclinm.2022.101817

Oral manifestation of the monkeypox virus: a systematic review and meta-analysis

Aravind Gandhi P a,k, Sourabha Kumar Patro b,k, Mokanpally Sandeep c, Prakasini Satapathy d, Muhammad Aaqib Shamim e, Vinay Kumar f, Arun Kumar Aggarwal g, Bijaya Kumar Padhi g,k,∗, Ranjit Sah h,i,j,∗∗
PMCID: PMC9815964  PMID: 36628187

Summary

Background

Mpox (formerly known as monkeypox) is a global public health concern, given the recent outbreaks in non-endemic countries where little scientific evidence exists on the disease epidemiology. Oral lesions among mpox cases have been poorly reported. Our aim was to estimate the overall prevalence of oral manifestations among patients with mpox globally.

Methods

In this systematic review and meta-analysis, an extensive literature search in PubMed, Scopus, Web of Science, Embase, Cochrane, and preprint servers (medRxiv, arXiv, bioRxiv, BioRN, ChiRxiv, ChiRN, and SSRN) and assessment of all published articles, conducted across the world, until Nov 15 2022 as per the PROSPERO registration protocol (CRD42022371249), was undertaken. Primary studies (case series, cross-sectional, retrospective, prospective designs) that reported the oral/oropharyngeal symptoms among laboratory-confirmed mpox cases were included. The characteristics of the study, information on the number of cases, and symptomatic status were extracted from the included studies. The quality of the included studies was assessed for bias. Random-effects meta-regression with DerSimonian & Laird estimator, and subgroup analyses were conducted using STATA (v17.0). The degree of funnel plot asymmetry was assessed using Egger's test when at least 10 estimates were available. The heterogeneity between studies was assessed using the I2 statistic. The primary outcome was the pooled prevalence of oral manifestations in the examined population.

Findings

19 studies were included with 4042 laboratory-confirmed patients with mpox for qualitative and quantitative synthesis. The pooled prevalence of oral manifestations in the investigated population was 36.75% (95% confidence interval [CI]: 23.77–50.65). Heterogeneity was found to be high in the current meta-analysis (I2 = 98.24%; p < 0.001). Subgroup analysis revealed a pooled prevalence of 39.96% (95% CI: 21.42–59.91) of sore throat, 24.80% (95% CI: 8.14–46.32) of mouth sore, 18.24% (95% CI: 0.34–52.54) of tonsillitis and 17.99% (95% CI: 15.66–20.43) of mouth rash from the included studies.

Interpretation

Oral manifestations are common in patients with mpox, with variations in prevalence across the sites within the oral cavity, and geography of the studies. Healthcare workers should be wary of the oral signs and symptoms of mpox in endemic and high-risk areas.

Funding

None.

Keywords: Monkeypox, Oral manifestation, Infection, Transmission, Oropharyngeal lesions

Research in context.

Evidence before this study

Oral mucous membranes are affected in almost 70% of cases, making it one of the most common areas involved in mpox. However, the documentation of oral lesions has been poor in the literature. Based on our systematic search, although multiple studies reported the prevalence of various oral manifestations, a pooled effect and site-wise presentations of oral and oropharyngeal lesions were not available. In this context, the following systematic review and meta-analysis was conducted after an extensive literature search in PubMed, Scopus, Web of Science, Embase, Cochrane, and preprint servers (medRxiv, arXiv, bioRxiv, BioRN, ChiRxiv, ChiRN, and SSRN) and assessment of all eligible articles which were available until Nov 15 2022 as per the PROSPERO registration protocol (CRD42022371249).

Added value of this study

The pooled prevalence of oral manifestations in the patients with mpox was 36.75% (95% confidence interval [CI]: 23.77–50.65) from 19 studies. Subgroup analysis revealed a pooled prevalence of 39.96% (95% CI: 21.42–59.91) of sore throat, 24.80% (95% CI: 8.14–46.32) of mouth sore, 18.24% (95% CI: 0.34–52.54) of tonsillitis and 17.99% (95% CI: 15.66–20.43) of mouth rash from the included studies. As per our knowledge, this is the first SR/MA which included studies across multiple databases of published and unpublished literature to quantify and study the prevalence of site wise oral lesions in mpox. The prevalence of oral lesions varied according to the endemicity: endemic countries [62.67% (95% CI: 52.75–72.12)] and non-endemic countries [15.62% (95% CI: 10.24–21.69), and broad geography: Europe 15.07% (95% CI: 7.02–24.95), Africa 62.67% (95% CI: 52.75–72.12) and North America 27.48% (95% CI: 7.19–52.99).

Implications of all the available evidence

Oral and oropharyngeal lesions are prevalent among 36.75% of patients with mpox. The sore throat was the most common oropharyngeal lesion in mpox. The clinical examination performed specifically for patients with mpox, and the general examination for other patients in high-risk areas of mpox should include oral examination in order to ascertain the oral lesions to suspect mpox. Future studies should describe the site-wise oral lesions and oral lesions linked with high-risk sexual practices to understand better the association between site-specific oral lesions, sexual practices and mpox.

Introduction

Zoonoses have been attributed to approximately 60% of emerging infectious diseases worldwide.1 Mpox (formerly known as monkeypox) is an emerging zoonosis caused by a virus belonging to the genus orthopoxvirus in the poxviridae family.2 Although the monkeypox virus was identified in 1958, the first human case was reported in the Democratic Republic of Congo in 1970.3 Up to 2003, mpox outbreaks were limited to the West, and Central African countries,2 with the first non-African outbreak reported in the United States of America (USA) in 2003. Since then, sporadic outbreaks in other countries, with an epidemiological link to endemic African countries, have been reported until 2021. A multicountry outbreak of mpox has been reported since May 13 2022.2 Taking into account the risk profile, the World Health Organization (WHO) declared mpox a Public Health Emergency of International Concern (PHEIC) on 23 July 2022.4 Globally, a moderate risk has been attributed to mpox, with Europe and the Americas designated as high-risk regions.5 As of Nov 27 2022, total laboratory-confirmed cases of monkeypox are 81,107, spanning 110 countries.5 The monkeypox virus is transmitted through direct contact with an infected person/animal or indirectly through contaminated materials.2 Smallpox vaccines are also protective against mpox. However, since the younger population is not vaccinated against smallpox, they are the most vulnerable to mpox.2

Although mpox is primarily a self-limiting disease, considerable mortality has been associated with it. The case fatality rate (CFR) ranged from 0 to 11% during the pre-2022 outbreaks. The ongoing 2022 multicountry outbreak reported a CFR of 3–6%.2 The CFR also varies between the West African and Central African clades (3.6% vs 10.6%).6 Morbidity in severe cases has been reported among the paediatric population and immunodeficient patients. After an incubation period ranging from 5 to 21 days, mpox manifests itself mainly through nonspecific symptoms such as fever, headache, myalgia, fatigue, and lymph node enlargements.2,7 Skin lesions were observed in 95% of the cases reported.8 The most common symptom is rashes.9 Rashes in monkeypox usually appear within 1–3 days after the incidence of fever, and are concentrated in the face and extremities.2 Rash indicates the initiation of the infectious period in the mpox case.10 The rashes are mostly pleomorphic and follow a centrifugal distribution. These cutaneous lesions were also reported in the oral cavity in approximately 39% of mpox cases. Complications included ulceration and necrosis of the rashes, among others.9

The epidemiology of mpox has been evolving over time, with varied risk, symptom and outcome profiles.6,11 The transition in epidemiological features was evidenced during the multicountry outbreak.9 A better understanding of the spectrum and proportion of specific clinical manifestations will help to understand and improve the response to current and future outbreaks. Oral manifestations have been presented since the dissemination of mpox epidemiology in the 1980s.12

The oropharynx is one of the routes of transmission of the monkeypox virus.13 Oral mucous membranes are affected in almost 70% of cases, making it one of the most common areas involved in mpox.2 Oral ulcers have been reported among 96% of laboratory-confirmed cases.10 Oral lesions have been reported to occur even before rashes appear on the skin.14 Mouth sores have been associated with hospitalisation in mpox cases,13 indicating the severity. Therefore, oral manifestations, in general, and depending on the area of involvement, may be necessary to identify the cases much earlier as well as in the prognosis. However, the documentation of oral lesions has been poor in the literature.15

A detailed review of the literature on oral manifestations and location of lesions in the oral cavity revealed tonsils, followed by the lips and tongue, as the most common locations of oral lesions.16 They also reported tonsillar swelling with pain in the throat as a major oral manifestation.16 However, it was a scoping review conducted until July 2022, when the case numbers were around 3000.16 Tonsil involvement leading to tonsillar abscess is a potential threat to airway patency.17 Based on our systematic search, although multiple studies reported the prevalence of various oral manifestations, a pooled effect and site-wise presentations of oral and oropharyngeal lesions were not available. In this context, the following systematic review and meta-analysis have been performed to provide updated information on the characteristics and sites of oral lesions, and to estimate the prevalence of various oral manifestations of mpox.

Methods

Search strategy and selection criteria

Our search was centred on the PICO criteria (Annexure 2) with the research question, “What is the prevalence of various oral manifestations in patients with mpox?”. We included five databases: PubMed, Scopus, Web of Science, EMBASE, and Cochrane. The pre-print servers (medRxiv, arXiv, bioRxiv, BioRN, ChiRxiv, ChiRN and SSRN) were also included in our search strategy (Annexure 3). Furthermore, new eligible studies were extracted by carefully searching for relevant references from the included papers and other suitable reviews. Using summary estimates, the primary outcome was the percentage of oral manifestations among the patients confirmed with mpox. The study has been registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42022371249.

The search keywords included ‘Monkeypox virus’, ‘MPXV’, ‘Monkeypox’, “oral manifestation” and “oral lesions”. MeSH terms with an asterisk were used to identify related articles in the study title (Annexure 3). Articles were saved in Mendeley Desktop V1.19.5 software to manage citations, remove duplicates, and co-ordinate the review process.

Data extraction and management

Two authors (AGP & SM) independently reviewed the title abstracts of the studies obtained from the above systematic search. If there was a disagreement regarding the inclusion of a study for full-text review, the co-authors conversed among themselves to build consensus. If there was still a conflict between the co-authors about the eligibility of the publication, a third co-author (BKP) was consulted to assess the title abstracts, and he decided whether to include the study for full-text review. Eligible full-text articles were reviewed for data extraction. Data extraction was done by two authors independently (AGP & SM). Contradictions in data extraction between the authors were removed in a consensus meeting conducted at the end of the independent extraction. Irresolvable contradictions were adjudicated by the third author (BKP). A final data extraction table was prepared in a Microsoft Excel spreadsheet for further analysis. The following information was gathered from each of the final eligible articles: the author's name, the place where the study was conducted, the year of publication, the study design, the number of infected cases, and positive cases, with a focus on capturing cases of oral manifestation of mpox.

The articles searched were reported using the Preferred Reporting Standard of Systematic Reviews and Meta-Analysis (PRISMA) flow-chart and Meta-analyses Of Observational Studies in Epidemiology (MOOSE) checklist to ensure scientific precision (Fig. 1 & Annexure 1).

Fig. 1.

Fig. 1

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PRISMA flow chart. Flow chart showing included studies in systematic review and meta-analysis of oral manifestation of monkeypox virus.

Inclusion and exclusion criteria

All articles published until 15 November 2022 were considered for this study (Annexure 2).

Quality assessment

For the cross-sectional studies and case series studies, two authors (AGP & SM) independently rated the studies using the National Heart, Lung, and Blood Institute (NHLBI) quality assessment tools. Sensitivity analysis was done after excluding the studies rated as poor quality.

Data analysis

The prevalence of oral manifestations was calculated by dividing the number of patients with oral manifestations by the total number of study participants. The heterogeneity of the studies was assessed using the I2 test. To address the risk of bias, we have conducted a sensitivity analysis by excluding poor-quality studies. A subgroup analysis was also performed to identify the pooled prevalence of oral lesions, according to the site in the oral cavity, from the included studies. We also undertook three more sub-group analysis to identify the source of heterogeneity: i) geography (continent-wise); ii) endemicity of the monkeypox virus (endemic vs non-endemic countries); and iii) reporting of sexual practices. A random effect regression model with DerSimonian & Laird estimator was used to evaluate the overall effect. Publication bias was assessed by funnel plot. Trim-and-fill test was conducted to address the publication bias, if any. Eggers test was applied to evaluate the small study effects. A p < 0.05 was considered statistically significant. STATA® software (version 17, STATA Corp.) was used to conduct the meta-analysis.

Ethical statement

Ethical review was not applicable since it was a systematic review and meta-analysis of the data from published literature.

Role of the funding source

There was no funding source for this study. All authors had full access to all the data in the study and had the final responsibility for the decision to submit for publication.

Results

The systematic search yielded 185 articles, among which 77 duplicates were detected. The title/abstract screening of the 108 articles was done, and 31 articles were found to be ineligible and removed. Full-text screening was performed on 77 articles after considering eligibility. Among them, 59 articles that did not satisfy the eligibility criteria were eliminated. In total, 19 studies were found to be eligible and included for systematic review and meta-analysis. The PRISMA flow chart depicts the article review and selection process (Fig. 1). The quality assessment of the findings of the included study is illustrated in the supplement file (Annexures 4a and 4b). Of the 19 studies, 13 (68.4%) were found to be fair or good quality.

The included studies were conducted over a period of time from 1988 to 2022. The baseline characteristics of 19 studies included in the meta-analysis, including eight cross-sectional studies,12,18, 19, 20, 21, 22, 23, 24 four case series,8,17,25,26 three prospective observational studies,27, 28, 29 and four retrospective studies,30, 31, 32, 33 are enumerated in Table 1. Most studies were carried out in countries where mpox was not endemic (13, 68.4%). Seven (36.8%) of the 19 studies were conducted in Nigeria, Sudan (earlier when South Sudan was part of larger Sudan) and the Democratic Republic of Congo, which are mpox-endemic countries. The studies had sample sizes ranging from 2 (Vaughan et al.) to 1195 (Philbott et al.).22,26 The highest prevalence of oral manifestation was observed in the studies conducted in Democratic Republic of Congo12,34 and USA,25 while the lowest was identified in Portugal.31 The prevalence ranged from 6.38% to 100%.

Table 1.

Baseline characteristics of monkeypox patients presenting with oral manifestations (N = 19 studies).

Author Study design Sample Prevalence OM type Age Participants
Male Female
Cassir et al. (2022) Retrospective observation analysis 129 8.52% Oral/perioral lesions, sore throat, tonsilitis 36 years (median, IQR 30–42) Male Female
Catala et al. (2022) Prospective cross-sectional study 185 14.05% Mouth sore 38.7 years (median) Male -
De Sousa et al. (2022) Retrospective observation analysis 47 63.8% Oral lesions 35.1 years (mean) Male -
Formenty et al. (2005) Cross-sectional 8 75% Mouth ulcers 8 months–32 years Male Female
Girometti et al. (2022) Retrospective observational study 54 20.37% Oropharyngeal lesions, sore throat 41 years (median, IQR 34–45) Male -
Huhn et al. (2005) Cross-sectional 34 20.58% Sore throat, mouth sores 6–47 years Male Female
Jazek et al. (1998) Cross-sectional 295 70.16% Oral lesions, tonsilitis 1 month–69 years Male Female
Martin-Filho et al. (2022) Cross-sectional 3 66.66% Oral lesions, sore throat 12–28 years Male Female
Ogoina et al. (2019) Cross-sectional 21 53.38% Sore throat, mouth sore and tongue sore 22–43 years Male Female
Ogoina et al. (2020) Retrospective study 40 45% Mouth rashes, sore throat 28 days–54 years Male Female
Patel et al. (2022) Descriptive case series 197 16.75% Oral lesions, sore throat 21–67 years Male -
Philpott et al. (2022) Cross-sectional 1004 17.77% Mouth/lips/oral mucosa rash 35 years (median, IQR 30–41) Male Female
Pittman et al. (2022) Prospective observational study 216 77.77% Oral/oropharyngeal lesions, sore throat 0–61 years Male Female
Sejvar et al. (2004) Cross-sectional 3 100% Oral lesions, sore throat 6–33 years Male Female
Thornill et al. (2022) Case series 528 12.50% Oropharyngeal lesions 21–62 years Male -
Vaughan et al. (2018) Cross-sectional 2 50.00% Oral lesions - Male -
Vicinte et al. (2022) Prospective observational study 181 36.46% Tonsilitis, sore throat 31–42 years Male Female
Whitehouse et al. (2021) Cross-sectional 1018 55.99% Buccal ulcers 1 month–79 years Male Female
Yinka-Ogunleye et al. (2019) Cross-sectional 77 58.44% Sore throat 2 days–50 years Male Female
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A meta-analysis was conducted to determine the prevalence of oral manifestations of human mpox infection among 4042 individuals in the included studies. Among them, 1433 had oral manifestations. The pooled prevalence of oral manifestations in the investigated population was 36.75% (95% confidence interval [CI], 23.77–50.65). Heterogeneity was found to be high in the current meta-analysis (I2 = 98.24%; p < 0.001) (Fig. 2). A random-effects model was applied. It is evident from the bubble graph that studies with a higher prevalence of oral manifestations tend to have a larger sample size (Annexure 5). The layout of the funnel plot showed an asymmetrical funnel (Annexure 6). Trim-and-fill method was found to be β: 0.355; 95% CI: 0.324–0.385, and no adjustment was made for publication bias (zero imputed studies) (Annexure 7). Eggers statistics revealed no small study effect (0.68, p-0.267). A sensitivity analysis was conducted by removing poor-quality studies (six numbers). However, we observed that it had no impact on the overall estimates of the pooled prevalence of oral manifestations [36.45% (95% CI: 20.35–54.09)], which further supports that there was no publication bias (Annexure 8).

Fig. 2.

Fig. 2

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Forest plot of pooled magnitude of oral manifestations in monkeypox virus.

Subgroup analysis revealed a pooled prevalence of 39.96% (95% CI: 21.42–59.91) of sore throat, 24.80% (95% CI: 8.14–46.32) of mouth sore, 18.24% (95% CI: 0.34–52.54) of tonsillitis and 17.99% (95% CI: 15.66–20.43) of mouth rash from included studies (Fig. 3). Further, we analysed based on the reporting of the sexual behaviour of the mpox cases by the authors (Fig. 4). Eight studies have reported the sexual practices of patients with mpox. The sub-group analysis of these studies revealed a pooled prevalence of oral lesions as 16.17% (95% CI: 11.48–21.46). None of the studies reported the prevalence of oral lesions among patients with high-risk sexual practices. Sub-group analysis based on endemicity found a higher pooled prevalence of oral manifestations among the studies from endemic countries [62.67% (95% CI: 52.75–72.12)] than the non-endemic countries [15.62% (95% CI: 10.24–21.69)] (Annexure 9). Sub-group analysis conducted according to broad geography (continent of the study) revealed a varied prevalence of oral manifestations: Europe 15.07% (95% CI: 7.02–24.95), Africa 62.67% (95% CI: 52.75–72.12) and North America 27.48% (95% CI: 7.19–52.99) (Annexure 10). All the sub-groups analyses were reported to have a heterogeneity of >80% in the included studies.

Fig. 3.

Fig. 3

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Oral manifestations of monkeypox virus based on site of lesion.

Fig. 4.

Fig. 4

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Oral manifestations of the monkeypox virus based on sexual behavior (reported vs not reported) by the authors.

Our study revealed that the predominant oral manifestation in patients with mpox is sore throat (39.96%), followed by oral lesions (22.04%) (site unspecified). One of the prospective observational studies from the Democratic Republic of Congo reported a 77.78% prevalence of sore throat,34 while a case series of three patients reported sore throat among all patients.25 Similarly, Jazek et al., the oldest among the included studies (1988), reported that a 70% prevalence of oral lesions was observed in patients with mpox from the Democratic Republic of congo.12 Catala et al. observed that 5% of cases had oral ulcers and reported no difference between vaccinated and unvaccinated people against smallpox in terms of extension or number of lesions.29

Discussion

The present meta-analysis is the first study to estimate the pooled prevalence of oral manifestations among patients with mpox, to our knowledge. The pooled analysis included 4042 patients with mpox from 19 eligible studies from multiple countries between 1988 and 2022. The meta-analysis included 1775 patients from mpox-endemic countries (41.44%) and 2367 patients from non-endemic countries (58.56%). The pooled prevalence of oral manifestations among patients with mpox was estimated to be 36.75%.

A similar proportion of oral mucous membrane (39%) lesions was estimated in another meta-analysis that included six studies.9 Although a significant proportion, oral lesions were lower than mpox cardinal symptoms, such as a rash (93%–100%), fever (72%–96%), pruritis (65%) and lymphadenopathy (62%).9,10 Another review reported a 96% prevalence of oral ulcers as a symptom of mpox, including the overwhelming majority of patients from the Democratic Republic of the Congo. Oral lesions were present regardless of the source of transmission (Human & Animal).12 The prevalence of oral lesions was not uniform between regions. Although African studies reported a higher prevalence of oral manifestations (45%–77.78%), most of the studies from the Americas and Europe reported a prevalence of less than 40%.8,17,19,22,27,29, 30, 31, 32 This can be linked to the prevalence of high-risk contact and sexual practices (multiple sexual partners in the 12 weeks prior to the diagnosis of monkeypox or use of recreational drugs during sex) in behaviour,27 and high incidences of immunocompromised diseases such as HIV.33 Similar geographical variation in the prevalence of rashes, in general, was reported in another review.9 However, myalgias and lymphadenopathy did not show such variations between regions.9

The sore throat was reported in 39.96% of the mpox cases in the present analysis. A higher prevalence of sore throat of 57% was reported in a previous meta-analysis.9 Within the oral cavity, various sites such as the lips, tongue and tonsils have been affected in previous case reports.16 In the present meta-analysis, mouth sores were estimated in 24.80% of cases, while tonsils were affected in 18.24%. Mouth rash was found in 37.15% of the cases, and tongue sores were present in 9.52% of the cases included in the analysis. In particular, the site of oral manifestations also varied by geography. The sore throat was commonly observed in three different studies conducted in Nigeria21,33,24 whereas the Europe31 and UK32 patients reported oral lesions (site unspecified).

Early suspicion and subsequent identification of patients with mpox will enable effective prevention of disease transmission. Oral lesions have been shown to appear earlier than skin lesions and, in some cases, skin eruptions began from the mouth.13,35 A multicountry study found that 26 patients reported oropharyngeal symptoms as their initial symptoms.8 The chances of asymptomatic spread further aggravate the concerns, emphasising the need for early detection.17 Other ways of early detection and detection of asymptomatic individuals, such as seroprevalence, are difficult in mpox, thus making early diagnosis and isolation more significant. The first fatal case from India, presenting with atypical symptoms with no skin lesions, was found to have tested positive for mpox from the oropharyngeal and nasopharyngeal samples only.36 Other studies have also highlighted the importance of the testing of the oropharyngeal swab for mpox, in the absence of cutaneous lesions.37,38 Thus, oropharyngeal manifestations can help in the early identification of potential mpox suspects in the endemic and outbreak regions. However, further analytical studies are required to confirm this hypothesis.

The prevalence of mouth sores was 24.80% among monkeypox cases. Mouth sores, tonsillar abscesses, and pharyngeal lesions have been reported to be one of the risk factors for hospitalisation in the mpox.17,19 Pharyngitis leading to restriction of oral intake has been reported to be the reason for 7.1% of hospitalisations.8 Studies have reported tonsilitis as a common complication that warranted medical therapy.27,30 Tonsillar ulcers with ensuing oedema and tonsillar abscess lead to difficulty in swallowing, thus ultimately compromising the airway.17,29 The high incidence of dysphagia and odynophagia in patients with oral and oropharyngeal mucosal lesions28,39 can be addressed and treated early. This leads to better quality of life and recovery along with a reduction in the chances of developing life-threatening complications of abscess and airway compromise as a sequel of oropharyngeal lesions.17,40 The same has been observed in the studies from Congo,23,28 where it was observed that the presence of oral and oropharyngeal lesions was mainly associated with higher severity of disease, further emphasising early detection and close clinical observation of the cases to ensure adequate medical care. This will also help in deciding on the administration of antiviral therapy.29

Considering the high proportion of oral and oropharyngeal lesions, it is of prime importance to conduct an oral examination as part of a suspected mpox clinical examination. The healthcare workers involved in mpox management must be sensitised about the varied oral and oropharyngeal manifestations of the disease.

Six among the included studies had incomplete details, with no exact site of the oral and oropharyngeal lesions. In the UK, the chance of mucocutaneous lesions, including anogenital lesions, in mpox-confirmed individuals practising high-risk sexual practices was 100 per cent, with many cases of oral and oropharyngeal lesions that risk transmission by virtue of contact through unsafe sexual practices.17 A study from Spain has also reported a very high incidence of oral inceptive and receptive sexual practice (87–88%).27 In order to measure the actual impact of the sexual practices, oral lesions reported among the patients with high-risk sexual practices were required. However, none of the studies was found to have reported the oral lesions categorised by sexual practices (high risk vs low risk). Hence, it is not possible to differentiate whether the oral lesions were due to high-risk sexual practice or due to viremia. It is hypothesised that these oral, oropharyngeal and genital mucosal lesions could have been the sites of inoculation, causing local inflammation before the virus spreads systematically. However, in the current epidemic, the disease spreads through close interaction, which can be social contact and not necessarily sexual contacts.8,17 Hence, localisation and isolation of people with oral lesions can help in epidemic control strategies.

Although many drugs have been used in mpox management, such as cidofovir, tecovirimat, and vaccinia Ig, being a self-limiting condition mainly without effective targeted drug therapy, prevention by effective isolation and containment, ensuring public health measures is the key to restricting the epidemic.8,16

This SR/MA included studies across multiple databases of published and unpublished literature to quantify and study the prevalence of oral lesions in mpox, which is the first of its kind, globally. It also presented the prevalence of oral manifestations according to the site of the lesion in the oral cavity. The risk of bias in the studies was assessed using standard tools. Six studies rated as poor quality was addressed by conducting a sensitivity analysis for the prevalence of oral lesion after excluding them. However, the present analysis was not devoid of limitations. There was significantly high heterogeneity among the included studies. It has been reported in the literature that high heterogeneity poses challenges in interpreting the findings from meta-analysis.41 Sub-group analysis is one method to address the issue by identifying the factors causing the heterogeneity. Although the sub-grouped meta-analysis (Geography, mpox endemicity, Reporting of sexual practices and site of oral cavity lesions) reduced the level of heterogeneity in comparison to the overall analysis in the present study, it was still considerably high (>80%). Application of random-effects model is one of the ways to undertake the meta-analysis of the studies which have high heterogeneity.41,42 However, there is no stringent and specific cut-off in heterogeneity levels to declare a particular meta-analysis unreliable. While interpreting the results of the meta-analysis by random-effects model with high heterogeneity, due discussion must be made on the limitations and potential reasons for the variability.42,43 Geography, endemicity, sexual practices and site-wise lesions could not explain the high heterogeneity among the included studies in the current meta-analysis. Hence, the heterogeneity in the oral manifestations prevalence reported in the present analysis might be due to biological reasons such as age, sex, race, clinical co-morbidities, and behavioural reasons such as high-risk sexual practices, specifically oral sex. Although we did a sub-group analysis on the studies based on their reporting of sexual practices, none of the studies reported the oral lesions according to the high-risk vs low-risk sexual practices. Thus, the pooled prevalence of the oral lesions in the study must be cautiously interpreted. Six of the studies did not report site-wise oral lesions.

Oral and oropharyngeal lesions are prevalent among 36.75% of patients with mpox. The sore throat was the most common oropharyngeal lesion in mpox. The presence of asymptomatic oral lesions further warrants high-risk screening for early identification by detecting suspicious enanthems and other mucosal lesions. Since the clinical severity of mpox has been associated with oral lesions, the physical examination performed specifically for patients with mpox, and the general examination for other patients in high-risk areas of mpox should include oral examination in order to ascertain the oral lesions to suspect mpox. Future studies should describe the site-wise oral lesions and oral lesions linked with high-risk sexual practices to understand better the association between site-specific oral lesions, sexual practices and mpox. Additionally, studies on the progress of oral and oropharyngeal lesions over the course of the disease must be conducted to understand the prognostic validity of these lesions in mpox.

Contributors

BKP, SP, AGP, RS, and AKA conceptualised the study and designed the protocol. MAS did the PROSPERO registration. AGP, PS, SP, and MS did the literature review, collected data and assessed the quality of the studies. AGP, SM, and VK verified the data. BKP and PS analysed the data. AGP, MAS, and MS interpreted the results. AGP, BKP, SP, and RS the initial draft of the manuscript. RS, AKA, and VK have reviewed, edited, and provided critical comments. Finally, AGP, BKP, and PS edited the final draft with the team's amendment of critical revisions and essential suggestions. All authors had full access to all the data in the study and had the final responsibility for the decision to submit for publication.

Data sharing statement

Documents containing all the extracted data have been made available in the manuscript and accompanying supplementary material.

Declaration of interests

None of the authors has declared any competing interests.

Footnotes

Appendix A

Supplementary data related to this article can be found at https://doi.org/10.1016/j.eclinm.2022.101817.

Contributor Information

Bijaya Kumar Padhi, Email: bkpadhi@gmail.com.

Ranjit Sah, Email: ranjitsah@iom.edu.np.

Appendix A. Supplementary data

Supplementary Material
mmc1.pdf (798.6KB, pdf)

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