Diagnostic and Prognostic Potential of Biochemical and Hematological Markers in Tobacco Users with Oral Pre-Cancer Lesions: Markers in Tobacco Users with Oral Pre-Cancer

Muhammad Rafique Tagar; Arsalan Ahmed; Muhammad Mustafa; Muzaffar Qayum Khan Ghauri; Muhammad Aqeel Aslam; Shakeel Ahmed Tagar; Shaharyar Ahsan

doi:10.54393/pjhs.v5i06.1708

Authors

Muhammad Rafique Tagar Department of Biochemistry, Bibi Aseefa Dental College, Shaheed Mohtarma Benazir Bhutto Medical University, Larkana, Pakistan
Arsalan Ahmed Department of Periodontics, Muhammad Dental College, Mirpurkhas, Pakistan
Muhammad Mustafa Department of Periodontics, Shahida Islam Dental College, Lodhran, Pakistan
Muzaffar Qayum Khan Ghauri Department of Orthodontics, Bhitai Dental and Medical College, Mirpurkhas, Pakistan
Muhammad Aqeel Aslam Department of Oral Medicine, Muhammad Dental College, Mirpurkhas, Pakistan
Shakeel Ahmed Tagar Institute of Pharmacology, Shaheed Mohtarma Benazir Bhutto Medical University, Larkana, Pakistan
Shaharyar Ahsan Department of Research and Development, Scientia Nova, Islamabad, Pakistan

DOI:

https://doi.org/10.54393/pjhs.v5i06.1708

Keywords:

Oral Premalignant Lesions, Biochemical Markers, Oral Cancer, Leukoplakia, Erythroplakia

Abstract

Oral Pre-Cancer Lesions (OPLs) including leukoplakia, erythroplakia, and submucous fibrosis denote biochemical and histopathologically altered changes in the oral mucosa marked by subcellular and structural anomalies evocating of potential for a malignant transformation, which is primarily caused by tobacco exposure. Early diagnosis is of paramount importance to halt the progression of premalignant lesions to high-grade dysplasia and even oral cancer. Objective: To find the diagnostic and prognostic potential of biochemical and haematological markers in Tobacco Users (TU) with OPL. Methods: PRISMA guidelines were followed to perform this systematic review. After retrieving 170 epidemiological studies published from 2013 to 2023, through multiple databases (PubMed, Google Scholar, Sci-hub, and Science Direct), 21 were included to determine the potential of biochemical and haematological markers in risk stratification and early detection of OPL. Results: According to the following systematic review, extracted data showed specific biochemical and haematological indicators that could serve as markers in risk stratification and early detection of OPL. The OPL group exhibited significantly higher levels of biochemical markers IL-6, IL-8, TNF-α, HCC-1, PF-4, FRR, TP, MDA, MMP-12, and Ceruloplasmin and hematological markers NLR, PLR, CRP, ESR, WBC, and low Hb as compared to the control group. Following risk stratification, a group with older age, tobacco association with OPL, and elevated levels of markers were categorised as a higher-risk group. Conclusions: The biochemical and haematological markers are potential promising markers in the early detection of OPL from malignant lesions with diagnostic and prognostic significance.

References

Awadallah M, Idle M, Patel K, Kademani D. Management update of potentially premalignant oral epithelial lesions. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology. 2018 Jun; 125(6): 628-36. doi: 10.1016/j.oooo.2018.03.010. DOI: https://doi.org/10.1016/j.oooo.2018.03.010

Pawar U and de Souza C. Precancerous lesions of oral cavity. An International Journal of Otorhinolaryngology Clinics. 2010 Aug; 2(1): 7-14. doi: 10.5005/jp-journals-10003-1012. DOI: https://doi.org/10.5005/jp-journals-10003-1012

Panwar A, Lindau R, Wieland A. Management for premalignant lesions of the oral cavity. Expert Review of Anticancer Therapy. 2014 Mar; 14(3): 349-57. doi: 10.1586/14737140.2013.842898. DOI: https://doi.org/10.1586/14737140.2013.842898

Van der Waal I. Oral leukoplakia, the ongoing discussion on definition and terminology. Medicina Oral, Patologia Oral Y Cirugia Bucal. 2015 Nov; 20(6): e685. doi: 10.4317/medoral.21007. DOI: https://doi.org/10.4317/medoral.21007

Van der Meij EH, Mast H, van der Waal I. The possible premalignant character of oral lichen planus and oral lichenoid lesions: a prospective five-year follow-up study of 192 patients. Oral Oncology. 2007 Sep; 43(8): 742-8. doi: 10.1016/j.oraloncology.2006.09.006. DOI: https://doi.org/10.1016/j.oraloncology.2006.09.006

Mello FW, Miguel AF, Dutra KL, Porporatti AL, Warnakulasuriya S, Guerra EN et al. Prevalence of oral potentially malignant disorders: a systematic review and meta‐analysis. Journal of Oral Pathology & Medicine. 2018 Aug; 47(7): 633-40. doi: 10.1111/jop.12726. DOI: https://doi.org/10.1111/jop.12726

Petti S. Pooled estimate of world leukoplakia prevalence: a systematic review. Oral Oncology. 2003 Dec; 39(8): 770-80. doi: 10.1016/S1368-8375(03)00102-7. DOI: https://doi.org/10.1016/S1368-8375(03)00102-7

Kansara S and Sivam S. Premalignant Lesions of the Oral Mucosa. 2023 May 23.

Kusiak A, Maj A, Cichońska D, Kochańska B, Cydejko A, Świetlik D. The analysis of the frequency of leukoplakia in reference of tobacco smoking among northern polish population. International Journal of Environmental Research and Public Health. 2020 Sep; 17(18): 6919. doi: 10.3390/ijerph17186919. DOI: https://doi.org/10.3390/ijerph17186919

Goyal D, Goyal P, Sing HP, Verma C. Precancerous lesions of oral cavity. Oral Surg Oral Med Oral Pathol International Journal of Medical and Dental Sciences. 2012; 2: 70-1. doi: 10.18311/ijmds/2013/19825. DOI: https://doi.org/10.18311/ijmds/2013/19825

Choudhary A, Kesarwani P, Chakrabarty S, Yadav VK, Srivastava P. Prevalence of tobacco-associated oral mucosal lesion in Hazaribagh population: a cross-sectional study. Journal of Family Medicine and Primary Care. 2022 Aug; 11(8): 4705-10. doi: 10.4103/jfmpc.jfmpc_1990_21. DOI: https://doi.org/10.4103/jfmpc.jfmpc_1990_21

Gupta B, Gupta A, Singh N, Singh RB, Gupta V. Occurrence of Oral Premalignant Lesions Among Tobacco Users in a Tribal Population: A Systematic Review and Meta-Analysis. Cureus. 2023 Oct; 15(10): e47162. doi: 10.7759/cureus.47162. DOI: https://doi.org/10.7759/cureus.47162

Khan S, Sinha A, Kumar S, Iqbal H. Oral submucous fibrosis: Current concepts on aetiology and management-A review. Journal of Indian Academy of Oral Medicine and Radiology. 2018 Oct; 30(4): 407-11. doi: 10.4103/jiaomr.jiaomr_89_18. DOI: https://doi.org/10.4103/jiaomr.jiaomr_89_18

Pitiyage G, Tilakaratne WM, Tavassoli M, Warnakulasuriya S. Molecular markers in oral epithelial dysplasia. Journal of Oral Pathology & Medicine. 2009 Nov; 38(10): 737-52. doi: 10.1111/j.1600-0714.2009.00804.x. DOI: https://doi.org/10.1111/j.1600-0714.2009.00804.x

Sarode SC, Sarode GS, Tupkari JV. Oral potentially malignant disorders: A proposal for terminology and definition with review of literature. Journal of Oral and Maxillofacial Pathology. 2014 Sep; 18(1): S77-80. doi: 10.4103/0973-029X.141322. DOI: https://doi.org/10.4103/0973-029X.141322

Ganly I, Patel S, Shah J. Early stage squamous cell cancer of the oral tongue-clinicopathologic features affecting outcome. Cancer. 2012 Jan; 118(1): 101-11. doi: 10.1002/cncr.26229. DOI: https://doi.org/10.1002/cncr.26229

Tilakaratne WM, Sherriff M, Morgan PR, Odell EW. Grading oral epithelial dysplasia: analysis of individual features. Journal of Oral Pathology & Medicine. 2011 Aug; 40(7): 533-40. doi: 10.1111/j.1600-0714.2011.01033.x. DOI: https://doi.org/10.1111/j.1600-0714.2011.01033.x

Tatehara S and Satomura K. Non-invasive diagnostic system based on light for detecting early-stage oral cancer and high-risk precancerous lesions-potential for dentistry. Cancers. 2020 Oct; 12(11): 3185. doi: 10.3390/cancers12113185. DOI: https://doi.org/10.3390/cancers12113185

Sarode GS, Sarode SC, Maniyar N, Sharma N, Yerwadekar S, Patil S. Recent trends in predictive biomarkers for determining malignant potential of oral potentially malignant disorders. Oncology Reviews. 2019 Jul; 13(2): 424. doi: 10.4081/oncol.2019.424. DOI: https://doi.org/10.4081/oncol.2019.424

Mishra R. Biomarkers of oral premalignant epithelial lesions for clinical application. Oral Oncology. 2012 Jul; 48(7): 578-84. doi: 10.1016/j.oraloncology.2012.01.017. DOI: https://doi.org/10.1016/j.oraloncology.2012.01.017

Dikova V, Jantus-Lewintre E, Bagan J. Potential non-invasive biomarkers for early diagnosis of oral squamous cell carcinoma. Journal of Clinical Medicine. 2021 Apr; 10(8): 1658. doi: 10.3390/jcm10081658. DOI: https://doi.org/10.3390/jcm10081658

Saleem Z, Shaikh AH, Zaman U, Ahmed S, Majeed MM, Kazmi A et al. Estimation of salivary matrix metalloproteinases-12 (MMP-12) levels among patients presenting with oral submucous fibrosis and oral squamous cell carcinoma. BioMed Central Oral Health. 2021 Apr; 21(1): 205. doi: 10.1186/s12903-021-01571-7. DOI: https://doi.org/10.1186/s12903-021-01571-7

Javaraiah RK, David CM, Namitha J, Tiwari R, Benakanal P. Evaluation of salivary lactate dehydrogenase as a prognostic biomarker in tobacco users with and without potentially malignant disorders of the oral cavity. South Asian Journal of Cancer. 2020 Jun; 9(02): 093-8. doi: 10.1055/s-0040-1721174. DOI: https://doi.org/10.1055/s-0040-1721174

Ram B, Chalathadka M, Dengody PK, Madala G, Madala B, Adagouda JP. Role of Hematological Markers in Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma. Indian Journal of Otolaryngology and Head & Neck Surgery. 2023 Sep; 75(3): 2054-62. doi: 10.1007/s12070-023-03803-4. DOI: https://doi.org/10.1007/s12070-023-03803-4

Krishnan R, Thayalan DK, Padmanaban R, Ramadas R, Annasamy RK, Anandan N. Association of serum and salivary tumor necrosis factor-α with histological grading in oral cancer and its role in differentiating premalignant and malignant oral disease. Asian Pacific Journal of Cancer Prevention. 2014; 15(17): 7141-8. doi: 10.7314/APJCP.2014.15.17.7141. DOI: https://doi.org/10.7314/APJCP.2014.15.17.7141

López-Jornet P, Olmo-Monedero A, Peres-Rubio C, Pons-Fuster E, Tvarijonaviciute A. Preliminary Evaluation Salivary Biomarkers in Patients with Oral Potentially Malignant Disorders: A Case-Control Study. Cancers. 2023 Nov; 15(21): 5256. doi: 10.3390/cancers15215256. DOI: https://doi.org/10.3390/cancers15215256

Gleber-Netto FO, Yakob M, Li F, Feng Z, Dai J, Kao HK et al. Salivary biomarkers for detection of oral squamous cell carcinoma in a Taiwanese population. Clinical Cancer Research. 2016 Jul; 22(13): 3340-7. doi: 10.1158/1078-0432.CCR-15-1761. DOI: https://doi.org/10.1158/1078-0432.CCR-15-1761

Ameena M and Rathy R. Evaluation of tumor necrosis factor: Alpha in the saliva of oral cancer, leukoplakia, and healthy controls-A comparative study. Journal of International Oral Health. 2019 Mar; 11(2): 92-9. doi: 10.4103/jioh.jioh_202_18. DOI: https://doi.org/10.4103/jioh.jioh_202_18

Punyani SR and Sathawane RS. Salivary level of interleukin-8 in oral precancer and oral squamous cell carcinoma. Clinical Oral Investigations. 2013 Mar; 17: 517-24. doi: 10.1007/s00784-012-0723-3. DOI: https://doi.org/10.1007/s00784-012-0723-3

Jureti M, Cerovi R, Belušić-Gobi M, Pršo IB, Kqiku L, Špalj S et al. Short Communication Salivary Levels of TNF-α and IL-6 in Patients with Oral Premalignant and Malignant Lesions. Folia Biologica (Praha). 2013; 59(2): 99-102.

Mohideen K, Sudhakar U, Balakrishnan T, Almasri MA, Al-Ahmari MM, Al Dira HS et al. Malondialdehyde, an oxidative stress marker in oral squamous cell carcinoma-A systematic review and meta-analysis. Current Issues in Molecular Biology. 2021 Aug; 43(2): 1019-35. doi: 10.3390/cimb43020072. DOI: https://doi.org/10.3390/cimb43020072

Dineshkumar T, Ashwini BK, Rameshkumar A, Rajashree P, Ramya R, Rajkumar K. Salivary and serum interleukin-6 levels in oral premalignant disorders and squamous cell carcinoma: diagnostic value and clinicopathologic correlations. Asian Pacific Journal of Cancer Prevention. 2016; 17(11): 4899-4906. doi: 10.22034/APJCP.2016.17.11.4899.

Nimbal A, Ahirrao B, Vishwakarma A, Vishwakarma P, Wani AB, Patil AA. Comparative evaluation of GSH, total protein and albumin levels in patients using smokeless tobacco with oral precancerous and cancerous lesions. Medicine International. 2024 Mar; 4(2): 1-0. doi: 10.3892/mi.2024.139. DOI: https://doi.org/10.3892/mi.2024.139

Patil MB, Lavanya T, Kumari CM, Shetty SR, Gufran K, Viswanath V et al. Serum ceruloplasmin as cancer marker in oral pre-cancers and cancers. Journal of Carcinogenesis. 2021 Sep; 20: 15. doi: 10.4103/jcar.jcar_10_21. DOI: https://doi.org/10.4103/jcar.jcar_10_21

Vankadara S, Padmaja K, Balmuri PK, Naresh G, Reddy V. Evaluation of serum C-reactive protein levels in oral premalignancies and malignancies: A comparative study. Journal of Dentistry (Tehran, Iran). 2018 Nov; 15(6): 358. doi: 10.18502/jdt.v15i6.329. DOI: https://doi.org/10.18502/jdt.v15i6.329

Salema H, Joshi S, Pawar S, Nair VS, Deo VV, Sanghai MM. Evaluation of the Role of C-reactive Protein as a Prognostic Indicator in Oral Pre-malignant and Malignant Lesions. Cureus. 2024 May; 16(5): e60812. doi: 10.7759/cureus.60812. DOI: https://doi.org/10.7759/cureus.60812

Phulari RG, Rathore RS, Shah AK, Agnani SS. Neutrophil: Lymphocyte ratio and oral squamous cell carcinoma: A preliminary study. Journal of Oral and Maxillofacial Pathology. 2019 Jan; 23(1): 78-81. doi: 10.4103/jomfp.JOMFP_160_17. DOI: https://doi.org/10.4103/jomfp.JOMFP_160_17

Narang D, Mohan V, Singh P, Sur J, Khan F, Shishodiya S. White blood cells count as a pathological diagnostic marker for Oral pre-cancerous lesions and conditions: A Randomized Blind trial. European Journal of Biotechnology and Bioscience. 2014; 2(3): 27-9.

Shanthi M and Ganesh R. Complete blood count as a diagnostic marker in oral lesions. 2022 Aug.

Singh S, Singh J, Samadi FM, Chandra S, Ganguly R, Suhail S. Evaluation of hematological parameters in oral cancer and oral pre-cancer. International Journal of Basic & Clinical Pharmacology. 2020 Jul; 9(7): 1090. doi: 10.18203/2319-2003.ijbcp20202947. DOI: https://doi.org/10.18203/2319-2003.ijbcp20202947

Magdum DB, Kulkarni NA, Kavle PG, Paraye S, Pohankar PS, Giram AV. Salivary Neutrophil-to-Lymphocyte Ratio as a Prognostic Predictor of Oral Premalignant and Malignant Disorders: A Prospective Study. Cureus. 2024 Mar; 16(3): e56273. doi: 10.7759/cureus.56273. DOI: https://doi.org/10.7759/cureus.56273

Khanna V, Karjodkar F, Robbins S, Behl M, Arya S, Tripathi A. Estimation of serum ferritin level in potentially malignant disorders, oral squamous cell carcinoma, and treated cases of oral squamous cell carcinoma. Journal of Cancer Research and Therapeutics. 2017 Jul; 13(3): 550-5. doi: 10.4103/0973-1482.181182.