Oral submucous fibrosis (OSMF), first described in the early 1950s, is a premalignant condition predominantly seen in people of Asian descent. It is a chronic progressive disorder and its clinical presentation depends on the stage of the disease at detection. In 1966, Sirsat and Pindborg [1] defined OSMF as an insidious chronic disease affecting any part of the oral cavity and sometimes pharynx. It is associated with juxta-epithelial inflammatory reaction followed by fibroelastic changes in the lamina propria layer, leading to juxta-epithelial hyalinization along with epithelial atrophy, which leads to rigidity of the oral mucosa, proceeding to trismus and difficulty in mouth opening. Joshi [2] from Mumbai re-designated the condition as OSMF, implying its histological nature predominantly. Paymaster [3] first reported its precancerous potential. Rao [4] suggested that OSMF is a localized condition of collagen disease.

OSMF is most commonly seen in young adults between 25 and 35 years (2nd–4th decade). The onset of this disease is insidious and is often 2–5 years of duration. It is commonly prevalent in Southeast Asia and the Indian subcontinent. The prevalence rate of OSMF in India is about 0.2%–0.5%. OSMF is a potentially malignant disorder with the risk of malignant change in advanced cases being 7.6%.

Despite extensive research, there is a lack of a standardized treatment protocol. Currently, there are no universally accepted guidelines or standard operating procedures for the management of OSMF. Treatment strategies vary widely and primarily focus on symptomatic relief and improving mouth opening through pharmacological interventions, physiotherapy, and surgical approaches in advanced cases. Hyperbaric oxygen therapy (HBOT) has been proposed as a potential adjunctive treatment for OSMF due to its ability to enhance tissue oxygenation, reduce fibrosis, and promote angiogenesis. However, its role in the management of OSMF remains underexplored, with limited clinical evidence supporting its efficacy.

HBOT involves administering 100% oxygen at pressures typically ranging between 2 and 3 atmospheres. This results in a marked increase in oxygen concentration within the bloodstream (hyperoxemia) and body tissues (hyperoxia). Under normal conditions, oxygen is mainly carried by hemoglobin within red blood cells, with only a small fraction dissolved in plasma. However, under hyperbaric conditions, the amount of oxygen dissolved directly into plasma rises significantly. This elevated oxygen availability enhances delivery to poorly perfused or damaged tissues, thereby facilitating repair and supporting various healing mechanisms.

Therefore, this study aims to evaluate the potential benefits of incorporating HBOT into the conventional treatment regimen for OSMF. By comparing outcomes between patients receiving standard therapy alone and those undergoing HBOT in conjunction with standard therapy, this research seeks to determine whether HBOT offers any added advantage in improving clinical symptoms, enhancing mouth opening, and modifying disease progression. The findings of this study could contribute to the development of more effective treatment strategies and provide a basis for future recommendations in the management of OSMF.

Conventional treatment approaches for OSMF primarily focus on symptomatic relief and improving mouth opening through corticosteroid injections, physiotherapy, and surgical interventions in severe cases. However, newer adjunctive therapies, such as HBOT, are being explored for their potential benefits in managing OSMF. HBOT involves the administration of 100% oxygen at increased atmospheric pressure, which enhances tissue oxygenation, promotes angiogenesis, and accelerates fibrosis, potentially counteracting the pathological fibrosis seen in OSMF.

In this study, the age range of patients is 18 to 60 years, with a mean age of 35 years. In Group 1, mean age is 33.35 and in Group 2, mean age is 38.47 (p=0.086), thus both groups are comparable on this aspect. These values are consistent with a study by More et al. [5] in which minimum and maximum age of participants was 20 and 65 years respectively, with a mean age of 36.04+12.42 years. A study by Sirsat and Pindborg [1] showed incidence of OSMF with age range of 15 to more than 55 years. Out of 34 patients enrolled in our study, only three female participants were involved in the study. In Group 1, 88.2% patients were male and in Group 2, 94.1% patients were male (p=0.545), both groups were comparable in terms of distribution of sex.

In our study, out of 34 included patients, five patients were Grade I in Group 1 and 4 in Group 2, and 12 patients were Grade II OSMF and 13 in Group 2 (p=0.697). Thus, both groups are comparable on the basis of distribution of grades of OSMF. These results were consistent with studies conducted by More et al. [5] in which 54% of the patients had Grade II OSMF. The lower number of Grade I OSMF patients could be due to a lack of awareness among the general population and the absence of noticeable early symptoms. In the initial stages, symptoms are often mild or non-existent, leading many individuals to overlook the condition or dismiss it as a minor issue. As the disease progresses and symptoms become more severe— such as increased burning sensation, difficulty in mouth opening, and stiffness (Grade II)—patients are more likely to seek medical attention.

In Group 1, 70.6% of individuals had a chewing-only tobacco and areca nut habit, while 29.4% engaged in both chewing and smoking. In Group 2, 58.8% had a chewing-only habit, whereas 41.2% used both chewing and smoking. Our results are consistent with Liu et al. [6], in which they concluded that areca nut chewing is the main causative factor for OSMF. Slaked lime acts as a catalyst in causing inflammation of oral mucosa. They also concluded that tobacco smoking and alcohol consumption have an additive effect on OSMF.

A key finding was the significantly greater reduction in burning sensation in Group 1 (HBOT+conventional therapy) by the second follow-up (p=0.020). This suggests HBOT offers better symptomatic relief through enhanced oxygenation, reduced inflammation, and improved mucosal healing (Fig. 1). HBOT has demonstrated significant anti-inflammatory effects by modulating cytokine levels, reducing oxidative stress, and altering immune cell responses. Studies indicate that HBOT suppresses the production of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and myeloperoxidase, while simultaneously upregulating IL-10, a key anti-inflammatory cytokine [7]. It has been proposed that fibrosis around salivary glands in OSMF reduces saliva secretion, impairing mucin expression and mucous layer protection—contributing to the burning sensation. HBOT helps by enhancing tissue hydration and healing [8]. HBOT has antinociceptive effects in neuropathic and inflammatory pain by improving oxygenation, reducing cytokines, and enhancing nerve cell function— further supporting its role in reducing burning sensation in OSMF [9].

Pain in OSMF arises from multiple factors, primarily due to progressive fibrosis and stiffening of oral tissues. As collagen deposition increases, the elasticity of the oral mucosa and underlying tissues decreases, leading to restricted mouth opening and pain on movement. This pain is particularly exacerbated during mastication and speech, as any attempt to stretch the fibrosed tissues results in microtrauma, further inflammation, and ischemia. Pain scores followed a decreasing trend in both groups, with Group 1 showing a more pronounced reduction between baseline and the final follow-up. Intragroup comparison demonstrated a significant reduction in pain scores in Group 1 (p=0.014), whereas Group 2 did not show a significant change (p=0.508). This further reinforces the potential of HBOT (Fig. 2). HBOT has been shown to have analgesic effects in addition to its antiinflammatory properties. Chronic inflammatory conditions often contribute to persistent pain due to tissue hypoxia, oxidative stress, and the release of pro-inflammatory cytokines. HBOT alleviates pain by reducing inflammation, improving oxygenation, and modulating cytokine levels [7]. Our findings align with Efrati et al. [10], who reported that HBOT improved pain thresholds and physical function in fibromyalgia via neuroplasticity, reduced neuroinflammation, and better oxygenation— mechanisms also relevant in OSMF. HBOT is effective in reducing pain in myofascial pain syndrome by improving tissue oxygenation and suppressing pro-inflammatory cytokines, supporting its role in chronic pain conditions like OSMF [11].

Although, there was no significant increase in mouth opening upon intergroup comparison among both the groups, a statistically significant increase in mouth opening upon intragroup comparison was noted post-therapy (p<0.001) in Group 1 as compared to Group 2. At baseline, mouth opening comparison was insignificant (p=0.390). Thus, rendering both the groups comparable at baseline (Fig. 3) In one patient, increase of 4 mm in mouth opening was observed after intervention (Fig. 4). HBOT helps reduce fibrosis by decreasing the expression of markers such as α-smooth muscle actin, collagen type I, and fibronectin. It also inhibits the activation of fibroblasts triggered by transforming growth factor-β and lowers hypoxia-inducible factor-1α levels. Given that fibrosis in OSMF is largely driven by tissue hypoxia, the improved oxygenation and suppression of fibrotic factors through HBOT contribute to increased tissue flexibility and better mouth opening [12].

HBOT improves tissue oxygenation, modifies inflammatory responses, and promotes fibrolytic activity [13]. In OSMF, chronic hypoxia within fibrotic tissues leads to excessive collagen deposition, reduced vascularity, and progressive fibrosis, which contribute to restricted mouth opening. HBOT helps counteract these changes by increasing oxygen availability to hypoxic tissues, promoting angiogenesis, and stimulating fibroblast function to enhance tissue remodeling [14]. HBOT improves mouth opening in OSMF by enhancing angiogenesis and vascularization in fibrotic tissues. It stimulates vascular endothelial growth factor, improving oxygen delivery and tissue repair in hypoxic areas, aiding fibrotic band breakdown [14,15]. HBOT improves mouth opening by regulating fibroblast activity and collagen remodeling. It reduces excess type I collagen production and boosts matrix metalloproteinase activity, promoting fibrotic tissue breakdown [13]. It also encourages myofibroblast differentiation into a less fibrotic form, enhancing tissue flexibility. Romero-Valdovinos et al. [16] investigated the influence of HBOT on fibroblast growth and the expression of key growth factors such as insulin-like growth factor and transforming growth factor in keloid scars. Their study revealed that HBOT modulates fibroblast proliferation and gene expression, leading to controlled collagen deposition and reduced fibrosis. Our study supports the role of HBOT in improving oral function in OSMF by enhancing oxygenation, vascularization, and collagen remodeling. Greater mouth opening in the HBOT group aligns with findings in similar fibrotic conditions [11]. HBOT shows promise as a noninvasive adjunctive therapy, though larger trials are needed to standardize its use. Previously, decreased mouth opening by the patients could also be due to guarding effect by the patient in anticipation of pain. Since we have already discussed reduction in pain and burning sensation, thus allowing patient to open mouth to a wider range.

CRP levels significantly decreased post-treatment in both groups, with a greater reduction in Group 1 (HBOT group), indicating a stronger anti-inflammatory effect (p=0.033). This aligns with Sharma et al. [17], who found elevated CRP in OSMF and OSCC, highlighting inflammation’s role in disease progression. HBOT’s effect on lowering CRP is supported by Harlan et al. [18], who reported similar results in ulcerative colitis, attributing it to reduced cytokines and enhanced healing. In OSMF, HBOT helps reduce hypoxia-induced oxidative stress, modulates fibroblast activity, and promotes angiogenesis— leading to improved symptoms and tissue repair. The combination of HBOT, antioxidants, and intralesional injections showed faster symptomatic relief, particularly in burning sensation and pain during mouth opening.

Limitations of this study include the small sample size, which reduces the generalizability of the results, along with the short follow-up period, because of which long-term outcomes could not be considered. Criteria such as the burning sensation are subjective to individual perception, leading to possible reporting bias. Also, the current status of tobacco chewing habits can-not be fully controlled, affecting treatment response.

In conclusion, managing OSMF is challenging due to its progressive and irreversible nature. HBOT was well tolerated with no adverse effects, underscoring its safety and feasibility as a noninvasive adjunct. While it may not reverse fibrosis, it effectively reduces symptoms and improves quality of life. This study supports the use of HBOT as an effective adjunct in early and late stages of OSMF and underscores the need for future research with larger samples and molecular-level analysis. Future directions should include larger, long-term studies with molecular analysis to validate HBOT’s therapeutic potential and refine protocols. HBOT shows promise in integrated OSMF management, especially in resource-limited settings where noninvasive, effective options are needed.