Management of Vocal Process Granuloma: A Systematic Review and Meta-analysis

Summary

This meta-analysis evaluated the effectiveness of conservative and surgical treatments for vocal process granuloma by comparing response and recurrence outcomes across published studies. The study also assessed the relative outcomes of different therapeutic combinations and management strategies.

Abstract

Vocal process granuloma is a benign laryngeal lesion associated with high recurrence rates, and the optimal management strategy remains uncertain due to heterogeneous treatment approaches and variable outcomes. This systematic review and meta-analysis aimed to evaluate the efficacy of available conservative and surgical modalities, either in isolation or in combination, for the treatment of vocal process granulomas. Following PRISMA guidelines, PubMed, Scopus, Web of Science, Cochrane, and EMBASE databases were searched. Retrieved studies were screened according to predefined eligibility criteria, and two authors independently extracted data from the included studies. A total of 49 studies involving 2,818 patients were included, of which 29 studies reported overall response rates. Among these, 5 studies used surgical intervention and demonstrated a pooled rate ratio (RR) of 0.70, whereas 24 studies used conservative treatment and demonstrated a pooled RR of 0.83. In addition, four studies evaluated the use of botulinum toxin combined with proton pump inhibitors (PPI), showing a complete response rate of 0.756. Recurrence rates were assessed in 22 studies, including 14 on conservative treatment and 8 on surgical treatment, with pooled recurrence rates of 0.09 and 0.59, respectively. Three studies using PPIs combined with voice therapy demonstrated a recurrence rate of 0.009. Overall, conservative treatment was associated with improved symptom outcomes and lower recurrence rates compared with surgery alone, although interpretation is limited by heterogeneity and variability in protocols. Combinations of voice therapy with PPIs or botulinum toxin A injections with PPIs were associated with favorable outcomes in several studies. Surgery remains an important option for large or resistant granulomas; however, adjunctive nonsurgical treatment may help reduce recurrence. Further large, randomized trials are needed to minimize selection bias and strengthen the validity of these findings.

Introduction

A vocal process granuloma, also known as a laryngeal contact granuloma, is a benign hyperplastic lesion that occurs mostly in the arytenoid cartilage¹. This condition is rare but has a high recurrence rate (between 37%–92%)^2,3,4,5. Vocal process granulomas are more frequently encountered among males and are predominant among individuals in their 40s and 50s^6,7,8,9,10.

Several etiological theories have been proposed to explain vocal process granuloma. However, the exact etiology is not completely understood¹¹. Vocal abuse is considered the most common cause, responsible for 33% of cases, followed by laryngopharyngeal reflux (30%), and endotracheal intubation (23%)^{6,12,13,14,15,16,17,18}. Other contributing factors include chronic cough, smoking, throat infections, postnasal drip, habitual throat clearing, and psychosomatic disorders¹⁹. Typically, several factors interact, leading to a multifactorial granuloma of the vocal process. In some cases, the etiology remains undetermined (idiopathic vocal process granuloma)^11,20,21.

Mechanical injury (e.g., traumatic intubation), repetitive phonotrauma (e.g., vocal abuse), or chemical irritation (e.g., laryngopharyngeal reflux) injures the thin epithelium of the mucoperichondrium that covers the vocal process. The mucoperichondrium responds to this injury by initiating an inflammatory process. Long-term chronic inflammation results in the generation of hyperplastic granulation tissue, which forms a vocal process granuloma. Microscopic histological assessment shows perichondritis with infiltration of inflammatory cells and granulation tissue^22,23. Clinical examination revealed a unilateral or bilateral sessile or pedunculated mass on the medial surface of the posterior third of the vocal process, restricted to the arytenoid region, with a round, semicircular, or lobulated shape, and a smooth surface that was reddish, white, or translucent. Patients may present with voice changes, globus sensation, throat pain, odynophagia, and airway obstruction in severe cases¹.

Vocal process granulomas can be treated conservatively (to reduce inflammation) or surgically (to resolve the mass burden). For conservative treatment, identification of the etiology is essential, as treatment depends primarily on eliminating predisposing factors. Antireflux medications (e.g., proton pump inhibitors) are effective for symptom improvement and lesion regression in treating granulomas caused by laryngopharyngeal reflux^2,18,24. In cases of mechanical granuloma resistant to standard treatments, botulinum toxin A injection into the affected vocal fold has demonstrated favorable outcomes²⁵. Granulomas associated with vocal abuse respond well to speech and language therapy and voice re-education¹². Furthermore, corticosteroid administration (inhaled or injected) may reduce the ongoing inflammatory process and improve the condition of patients with vocal process granulomas^26,27. Surgical treatment is generally reserved for long-standing granulomas that are refractory to conservative treatment, as well as for recurrent or large lesions associated with airway obstruction^1,12,28. Additionally, when a tissue biopsy is required for pathological assessment, surgical excision is performed^1,12,28. Surgical treatment options include endoscopic excision under local or general anesthesia in addition to low-dose radiotherapy (preferred for refractory granuloma)⁴.

These treatment modalities can be used either alone or in combination. Several conservative approaches may be combined, and in some cases, surgical treatment may complement conservative management. However, outcomes vary significantly due to diverse clinical presentations and multifactorial etiologies. Some patients may show treatment resistance, while others may experience recurrence despite appropriate therapy. In clinical practice, treatment selection is influenced by multiple factors, including underlying etiology, lesion size, symptom severity, disease duration, and recurrence history^4,21. Although conservative therapy is generally regarded as the preferred initial management approach, the sequencing of medical, behavioral, and surgical interventions remains variable^1,28. The lack of standardized, evidence–based guidelines contributes to heterogeneity in clinical practice across institutions, which may influence treatment outcomes^4,21,28.

This systematic review and meta-analysis aimed to evaluate the efficacy of available conservative and surgical modalities, either in isolation or in combination, for treating vocal process granuloma. Unlike previous reviews, which have largely focused on isolated treatment outcomes or limited comparative synthesis, the present study provides an updated and comprehensive evaluation of the evidence, including both response and recurrence outcomes as well as an assessment of combined treatment strategies.

Protocol

The study followed the design principles outlined in the Cochrane Handbook for Systematic Reviews of Interventions and adhered to the reporting standards set forth by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines^29,30. The study protocol was registered using PROSPERO (registration number: CRD42024512257). This systematic review and meta-analysis were based exclusively on data from previously published studies; therefore, ethical approval and informed consent were not required. The completed PRISMA 2020 checklist is provided as Supplementary File 1.

Literature search
We conducted a comprehensive search of five databases: PubMed, Scopus, Web of Science, Cochrane Library, and EMBASE. The search encompassed articles published across all databases from their inception until July 2023. Furthermore, we reviewed all references cited in eligible articles and meta-analyses on the same topic to ensure no relevant citations were overlooked. The search strategy incorporated the following search terms: (“vocal process granuloma” OR “vocal granuloma” OR “contact granuloma” OR “vocal cord granuloma” OR “vocal fold granuloma” OR “laryngeal granuloma” OR “arytenoid granuloma”). Although broader terms were included, the review specifically focused on vocal process granulomas, which represent the most common site of laryngeal granulomas. The complete database-specific search strategies and Boolean operators used for each database are provided in the Supplementary Table 1.

Eligibility criteria
Two reviewers screened the retrieved references based on the eligibility criteria. Our systematic review employed the following criteria for study inclusion: studies involving patients diagnosed with vocal process granuloma, studies involving any surgical or conservative treatment, and studies with at least 5 patients. Studies describing granulomas of other laryngeal subsites (e.g., subglottic or supraglottic), as well as surgical site granuloma/mid-vocal fold granuloma, were also excluded. To ensure accuracy and consistency, any discrepancies during the evaluation process were resolved through discussion among the investigators or by consulting a third assessor.

Some studies were excluded for the following reasons: animal studies were not considered; studies not published in English; studies consisting only of abstracts; and unpublished study data.

Data extraction
The data extraction process used a standardized local data extraction sheet, tested on a sample of included studies before formal extraction, to ensure uniformity and accuracy among reviewers. The following information was collected from each study: first author's name, year of publication, details regarding the study arms, study site, study design, participant’s sex, duration of follow-up, granuloma size, granuloma type, inclusion criteria, primary endpoints, and conclusions drawn from each included study.

Additionally, we assessed the following outcomes: overall response rate, defined as any improvement as detected by the investigators in the included study; complete response rate, based on the complete disappearance of granuloma without symptoms; partial response rate, defined as partial improvement or narrowing of the granuloma, but still present with or without symptoms; no response rate, indicating the absence of any improvement; and recurrence rate, defined as the reappearance of granuloma after initial treatment response, as reported by each included study. Because follow-up durations varied among studies, a standardized timeframe for recurrence assessment could not be uniformly applied.

Risk of bias assessment
Two investigators independently assessed the quality of observational studies using the National Institutes of Health (NIH) quality assessment tool for observational cohort and cross-sectional studies, and the NIH quality assessment tool for Case Series studies, developed by the National Heart, Lung, and Blood Institute (NHLBI), NIH. The authors' evaluation was categorized as "good," "fair," or "poor" based on the scores obtained during the assessment process.

Data synthesis
For the purposes of this analysis, botulinum toxin injection was classified as a conservative (non-surgical) treatment because it does not involve tissue excision or lesion removal. This classification was based on procedural invasiveness and was applied consistently throughout the study. Because most included studies did not directly compare conservative and surgical interventions, we performed an indirect comparative meta-analysis based on pooled proportions from single-arm studies. Combined rate ratios (RRs) with 95% confidence intervals (CIs) were used to compare outcomes between treatment groups. This approach enabled comparison between treatment modalities despite the lack of sufficient head-to-head comparative studies. Given the considerable clinical heterogeneity among the pooled studies, we initially adopted a random-effects model for our analysis. We also assessed statistical heterogeneity among studies using the chi-squared test for I² statistics, where p < 0.1 indicated heterogeneity, and an I² value ≥ 50% indicated high heterogeneity. All statistical analyses were performed using Review Manager and Open Meta-Analyst software.

For the single-arm analysis, we evaluated categorical outcomes as pooled proportions with 95% CIs. We used a random-effects model on the DerSimonian-Laird method. To evaluate statistical heterogeneity across studies, we used the chi-squared test for I² statistics; p < 0.1 indicates heterogeneity, and I2 ≥ 50% suggests high heterogeneity.

Results

Literature search results
We performed a comprehensive literature search across five databases, identifying 1,828 studies. After removing duplicates, 994 studies remained eligible for further assessment. By screening titles and abstracts, we identified 75 articles suitable for a more in-depth evaluation. Of these, 26 articles were excluded, ultimately including 47 articles that met our meta-analysis criteria^2,3,4<...

Discussion

A diverse range of treatment modalities is available for vocal process granulomas. However, no consensus has been reached on the ideal treatment modality. We conducted a systematic review and meta-analysis to evaluate the efficacy of conservative and surgical treatment options, both in isolation and in combination, for vocal process granuloma. Our evaluation depended on both the treatment response and recurrence rates. Our analysis included data from 49 studies, comprising 42 cohort studies and 7 case series, with a tota...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Open Meta-Analyst	Center for Evidence Synthesis in Health, Brown University, Providence, RI, USA	—	Single-arm meta-analysis
Review Manager (RevMan)	The Cochrane Collaboration, London, UK	version 5.4	Indirect comparative meta-analysis