The Role of Predictive Biomarkers, Clinical Features, and Chemoprevention Strategies in the Malignant Transformation of Oral Potentially Malignant Disorders to Oral Squamous Cell Carcinoma: A Meta-Analysis

Azeem Hussain Soomro; Romeysah Adnan; Tooba Iqbal; Muniba Shah; Mahrukh Anees; Zahra Masud; Urwa Ilyas; Dura Fatima; Ayesha Shuaib

doi:10.70749/ijbr.v3i2.746

Authors

Azeem Hussain Soomro Dow Dental College, Dow University of Health Sciences, Karachi, Sindh, Pakistan.
Romeysah Adnan Riphah International University, Islamic International Dental College, Islamabad, Pakistan.
Tooba Iqbal Shifa College of Dentistry, Islamabad, Pakistan.
Muniba Shah Shifa College of Dentistry, Islamabad, Pakistan.
Mahrukh Anees Shifa College of Dentistry, Islamabad, Pakistan.
Zahra Masud Shifa College of Dentistry, Islamabad, Pakistan.
Urwa Ilyas Shifa College of Dentistry, Islamabad, Pakistan.
Dura Fatima Shifa College of Dentistry, Islamabad, Pakistan.
Ayesha Shuaib Shifa College of Dentistry, Islamabad, Pakistan.

DOI:

https://doi.org/10.70749/ijbr.v3i2.746

Keywords:

Oral Potentially Malignant Disorders, Oral Squamous Cell Carcinoma, Predictive Biomarkers, Chemoprevention, Malignant Transformation

Abstract

Background: Oral Potentially Malignant Disorders (OPMDs) pose a significant risk for progression into Oral Squamous Cell Carcinoma (OSCC), a leading cause of oral cancer-related mortality. Early detection and risk assessment are critical for timely intervention. This meta-analysis evaluates predictive biomarkers, clinical features, and chemoprevention strategies influencing the malignant transformation of OPMDs to OSCC. Methods: A systematic literature search was conducted across PubMed, Web of Science, Cochrane Library, and Scopus databases following PRISMA guidelines. Studies evaluating biomarkers, histopathological features, or chemopreventive treatments for OPMDs were included. Randomized controlled trials (RCTs), phase I and II clinical trials, and observational studies were analyzed. Statistical analysis, including heterogeneity assessment and bias evaluation, was performed using R software. Results: A total of 10 studies with 980 participants were included. PD-L1 expression, EGFR mutations, and histopathological dysplasia were identified as key predictive biomarkers, with PD-L1 showing a sensitivity of 80% and specificity of 75% for malignant transformation. Targeted therapies such as Nivolumab, Erlotinib, and chemopreventive agents, including Green Tea Extract and Vitamin A, demonstrated significant reductions in lesion progression. Smoking, betel quid use, and genetic mutations were strongly correlated with increased OSCC risk. Conclusions: This meta-analysis confirms that integrating predictive biomarkers with clinical risk assessment can enhance early detection and intervention for OPMDs at high risk of malignant transformation. Chemoprevention strategies show variable effectiveness, highlighting the need for individualized therapeutic approaches. Future research should focus on refining biomarker-based screening protocols and optimizing targeted chemoprevention to mitigate OSCC progression risk.

Downloads

Download data is not yet available.

References

Zhang, X., Kim, K., Zheng, Z., Bazarsad, S., & Kim, J. (2017). Nomogram for risk prediction of malignant transformation in oral leukoplakia patients using combined biomarkers. Oral Oncology, 72, 132–139. https://doi.org/10.1016/j.oraloncology.2017.07.015

Speight, P. M., Khurram, S. A., & Kujan, O. (2017). Oral potentially malignant disorders: risk of progression to malignancy. Oral Surgery Oral Medicine Oral Pathology and Oral Radiology, 125(6), 612–627. https://doi.org/10.1016/j.oooo.2017.12.011

Melguizo-Rodríguez, L., Costela-Ruiz, V. J., Manzano-Moreno, F. J., Ruiz, C., & Illescas-Montes, R. (2020). Salivary biomarkers and their application in the diagnosis and monitoring of the most common oral pathologies. International Journal of Molecular Sciences, 21(14), 5173. https://doi.org/10.3390/ijms21145173

Jiang, X., Wu, J., Wang, J., & Huang, R. (2019). Tobacco and oral squamous cell carcinoma: A review of carcinogenic pathways. Tobacco Induced Diseases, 17(April). https://doi.org/10.18332/tid/105844

Hung, K., Liu, C., Chiu, P., Lin, J., Chang, K., Shih, W., Kao, S., & Tu, H. (2015). MicroRNA-31 upregulation predicts increased risk of progression of oral potentially malignant disorder. Oral Oncology, 53, 42–47. https://doi.org/10.1016/j.oraloncology.2015.11.017

Dewan, A., Mitra, S., Arora, R., & Batra, U. (2020). Essentials of oral cancer. https://www.jaypeedigital.com/book/9789354650819

Porter, S., Gueiros, L. A., Leão, J. C., & Fedele, S. (2018). Risk factors and etiopathogenesis of potentially premalignant oral epithelial lesions. Oral Surgery Oral Medicine Oral Pathology and Oral Radiology, 125(6), 603–611. https://doi.org/10.1016/j.oooo.2018.03.008

Schoenfeld, J. D., Hanna, G. J., Jo, V. Y., Rawal, B., Chen, Y., Catalano, P. S., Lako, A., Ciantra, Z., Weirather, J. L., Criscitiello, S., Luoma, A., Chau, N., Lorch, J., Kass, J. I., Annino, D., Goguen, L., Desai, A., Ross, B., Shah, H. J., . . . Haddad, R. I. (2020). Neoadjuvant nivolumab or nivolumab plus ipilimumab in untreated oral cavity squamous cell carcinoma. JAMA Oncology, 6(10), 1563. https://doi.org/10.1001/jamaoncol.2020.2955

Nair, S. V., Joshi, A., Patil, V. M., Noronha, V., Sable, N., Mahajan, A., Dharavath, B., Gardi, N., Bal, M., Nair, D., Gupta, T., Laskar, S., Agarwal, J., Chaturvedi, P., Dutt, A., D’Cruz, A., Gupta, S., & Prabhash, K. (2019). A phase II randomized control trial of erlotinib in combination with celecoxib in patients with operable oral squamous cell carcinoma (OSCC): Erlo-Xib Study. Journal of Clinical Oncology, 37(15_suppl), 6054. https://doi.org/10.1200/jco.2019.37.15_suppl.6054

Mohamed, R. K., Elsayed, N. M., Mahmoud, S. A., & Gaweesh, Y. Y. (2024). Photobiomodulation versus corticosteroid in the management of erosive oral lichen planus: a randomized controlled clinical trial. BMC Oral Health, 24(1). https://doi.org/10.1186/s12903-024-03976-6

Klongnoi, B., Sresumatchai, V., Clypuing, H., Wisutthajaree, A., Pankam, J., Srimaneekarn, N., Shrestha, B., & Khovidhunkit, S. P. (2022). Histopathological and risk factor analyses of oral potentially malignant disorders and oral cancer in a proactive screening in northeastern Thailand. BMC Oral Health, 22(1). https://doi.org/10.1186/s12903-022-02646-9

McCarthy, C., Fedele, S., Ottensmeier, C., & Shaw, R. J. (2021). Early-Phase interventional trials in oral cancer prevention. Cancers, 13(15), 3845. https://doi.org/10.3390/cancers13153845

Tsao, A. S., Liu, D., Martin, J., Tang, X., Lee, J. J., El-Naggar, A. K., Wistuba, I., Culotta, K. S., Mao, L., Gillenwater, A., Sagesaka, Y. M., Hong, W. K., & Papadimitrakopoulou, V. (2009). Phase II Randomized, Placebo-Controlled Trial of Green Tea Extract in Patients with High-Risk Oral Premalignant Lesions. Cancer Prevention Research, 2(11), 931–941. https://doi.org/10.1158/1940-6207.capr-09-0121

William, W. N., Papadimitrakopoulou, V., Lee, J. J., Mao, L., Cohen, E. E. W., Lin, H. Y., Gillenwater, A. M., Martin, J. W., Lingen, M. W., Boyle, J. O., Shin, D. M., Vigneswaran, N., Shinn, N., Heymach, J. V., Wistuba, I. I., Tang, X., Kim, E. S., Saintigny, P., Blair, E. A., . . . Lippman, S. M. (2015). Erlotinib and the risk of oral cancer. JAMA Oncology, 2(2), 209. https://doi.org/10.1001/jamaoncol.2015.4364

Nagao, T., Warnakulasuriya, S., Nakamura, T., Kato, S., Yamamoto, K., Fukano, H., Suzuki, K., Shimozato, K., & Hashimoto, S. (2014). Treatment of oral leukoplakia with a low‐dose of beta‐carotene and vitamin C supplements: A randomized controlled trial. International Journal of Cancer, 136(7), 1708–1717. https://doi.org/10.1002/ijc.29156

Sankaranarayanan, R., Mathew, B., Varghese, C., Sudhakaran, P., Menon, V., Jayadeep, A., Nair, M., Mathews, C., Mahalingam, T., Balaram, P., & Nair, P. (1997). Chemoprevention of oral leukoplakia with vitamin A and beta carotene: an assessment. Oral Oncology, 33(4), 231–236. https://doi.org/10.1016/s0964-1955(97)00010-9