Oral Squamous Cell Carcinoma in the Paediatric Patient a Literature Review
Version 1. F1000Res. 2020; 9: 229.
Oral squamous cell carcinoma: metastasis, potentially associated malignant disorders, etiology and contempo advancements in diagnosis
Amr Bugshan
1Department of Biomedical Dental Sciences, College of Dentistry, Imam Abdulrahman Bin Faisal University, Dammam, 31441, Saudi Arabia
Imran Farooq
iDepartment of Biomedical Dental Sciences, Higher of Dentistry, Imam Abdulrahman Bin Faisal University, Dammam, 31441, Saudi Arabia
Peer Review Summary
| Review appointment | Reviewer proper noun(southward) | Version reviewed | Review status |
|---|---|---|---|
| 2020 Apr 14 | Ali Leghari | Version one | Canonical |
| 2020 Apr fourteen | Fatima Qadir and Ambreen Rehman | Version ane | Approved |
| 2020 April ix | Faisal Aljofi | Version one | Canonical |
Abstract
Oral squamous cell carcinoma (OSCC) is a usually occurring caput and neck cancer. Information technology has a high prevalence in sure parts of the earth, and is associated with a high mortality rate. In this review, we describe metastasis related to OSCC, and disorders that could lead to OSCC with mutual etiological factors. In add-on, a cursory account of the diagnosis of OSCC and role of salivary biomarkers in its early detection has also been highlighted. Google Scholar and PubMed search engines were searched with keywords including "oral squamous cell carcinoma", "OSCC", "oral cancer", "potentially malignant disorders in oral fissure", "etiological factors of OSCC", "diagnosis of OSCC", and "salivary biomarkers and OSCC" to gather the literature for this review. The review concludes that OSCC has the potential for regional likewise as distant metastasis, and many potentially cancerous diseases can transform into OSCC with the help of diverse etiological factors. Diagnosis of OSCC involves traditional biopsy, only salivary biomarkers could likewise exist utilized for early on recognition.
Keywords: Oral squamous prison cell carcinoma, Metastasis, Potentially malignant disorders, Etiological factors of OSCC, Diagnosis of OSCC
Introduction
1 of the commonest forms of cancer is head and cervix cancer ane. Its prevalence is different in diverse parts of the world; in unindustrialized countries, similar India, information technology is the cancer nigh commonly diagnosed in male patients whereas in the Western world, it is responsible for 1–4% of all cancers two. Lip, oral cavity, and oropharynx combined were responsible for nearly 4,47,751 new cancer cases with an estimated two,28,389 deaths in 2018, which accounts for ii.iv% of all cancer deaths 3. Among other cancers, head and neck cancer is fourteenth in terms of incidence simply thirteenth in terms of mortality iii. The Asian continent has the highest incidence and mortality rates of oral crenel and oropharynx cancers amidst all other countries 4. More than 90% of cancer cases in head and neck region are OSCCs ( Figure 1) 5. OSCC develops in the oral cavity and oropharynx and can occur due to many etiological factors, but smoking and booze remain the most mutual hazard factors especially in the Western world half dozen. In South Asian countries, consumption of smokeless tobacco and areca nut products are the main etiological factors associated with OSCC 7. Gene mutations may also crusade cancer development in the throat and oral cavity; nonetheless, no specific gene has been identified in OSCCs 8. Activation of proto-oncogenes (ras, myc, EGFR) or inhibition of tumor suppressor genes (TB53, pRb, p16) by ecology factors such as smoking, irradiation, and viral infection may increment the take chances of oral and oropharynx OSCC 9. Most of the oral and oropharynx OSCC cases occur in elderly male patients, with tonsils and tongue beingness the most commonly affected sites ten.
Figure 1.
Photomicrograph showing well differentiated oral squamous carcinoma cells displaying nuclear pleomorphism, mitosis, and loftier number of keratin pearls.
Image is courtesy of Dr. Faraz Kasti (Oral Pathology Sectionalization, Higher of Dentistry, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia). Written informed consent was obtained from the individual for publication.
In this review we have briefly described metastasis related to OSCC, some disorders that could transform into OSCC with associated common etiological factors. In addition, a brief account of the diagnosis of OSCC and function of salivary biomarkers in its early detection has likewise been highlighted. Google Scholar and PubMed search engines were searched with keywords including "oral squamous prison cell carcinoma", "OSCC", "oral cancer", "potentially malignant disorders in oral crenel", "etiological factors of OSCC", "diagnosis of OSCC", and "salivary biomarkers and OSCC" and our search revealed 500+ results. All the articles in languages other than English language and conference abstracts/presentations were excluded. Finally, 77 articles were selected for this study and included in our review.
Metastasis
Metastasis could be of two types; regional and/or distant metastasis, as discussed below.
Regional metastasis
In terms of regional metastasis, nodal metastasis transpires when tumor cells at the primary site penetrate lymphatic channels and migrate to regional lymph nodes in the neck, forming a micrometastasis xi. Lymph node metastasis is a critical prognostic indicator for oral and oropharyngeal carcinomas 12. The most common site for OSCC metastasis is cervical lymph nodes, and it reduces the survival rate past fifty% thirteen, 14. Cancer cells usually spread to the lymph nodes on the same side of the cancer primary site. However, contralateral or bilateral lymph nodes metastasis tin rarely occur 9. In histopathology, tumor cells dissemination exterior the lymph node capsule making the prognosis worse and reducing patient survival rate xi. Therefore, a thorough caput and neck lymph node inspection and palpation for all first-time patients should be performed to help in early detection of cancer, which volition increase the chances for successful treatment and meliorate prognosis 15.
Distant metastasis
For afar metastasis, carcinomas crave certain biological events in society to spread from the main tumor site to an anatomically afar site. Several steps are required for cancer cells to spread from their original site to the metastatic 1, as shown in the invasion-metastasis cascade 16. The cascade starts at the master tumor site where the cancer cells locally breach the basement membrane to invade the surrounding extracellular matrix and connective tissue 17. Then, the tumor cells move to lymphatic or blood vessels and travel to distant metastatic sites. At this point, tumor cells start to extravasate from the vessels into the stroma of the metastatic site 18. Initially, tumor cells use the metastatic tissue microenvironment to grow and form micrometastasis. Then, tumor cells expand and colonize to offset their own proliferative plan and class macroscopic metastasis xvi. The lung is the commonest site for distant metastasis for caput and cervix OSCC 19. Nonetheless, metastasis to other organs, such every bit mediastinal nodes, liver, and bone, take been also reported 19, 20. Distant metastasis worsens the prognosis and reduces the chances of successful treatment 21. Positive regional lymph node involvement, extracapsular invasion of tumor cells, and human papilloma virus negativity are key factors that increase the risk of primary tumor cell broadcasting to distant organs xx.
Potentially malignant disorders (PMDs) transforming into OSCC
Early on detection of cancer is a key gene for improved prognosis and increased patient survival rate. Fifty-fifty though the mouth tin be easily examined and assessed past straight visual inspection, most OSCC cases are not identified early 22. This nigh likely ensues because patients do non seek dental care on a regular basis and most oral cancers in the early stages are asymptomatic 22. Moreover, dentists may non be aware of the different clinical presentations of OSCC and misdiagnose cancers every bit reactive or benign lesions 23. In order to help early discovery and increase the prognosis of cancers, patient sensation about regularly visiting dentists and education of dental practice staff to advisedly examine the patients should exist raised 24.
There are many PMDs in the mouth that take the predisposition to transform into OSCC, a few of which are discussed beneath in detail.
Leukoplakia
The World Health Organization describes "a clinical diagnosis that include any white lesion (plaque or patch) on the oral mucosa that cannot be considered clinically or pathologically equally any other disease is a leukoplakia" 25. In 1975, Waldron et al. reviewed iii,256 clinical cases defined equally "leukoplakia" and found that effectually eighty% of the cases are diagnosed microscopically every bit either hyperkeratosis or acanthosis 26. They also reported that about 17% of the cases were potentially malignant lesions (12.two% balmy to moderate dysplasia and 4.v% astringent dysplasia or carcinoma in situ) and the diagnosis of OSCC was fabricated in near 3% of the cases that were received with the diagnosis of "leukoplakia" 26. Earlier, Bewley and Farwell too reported that OSCC tin can occur from malignant transformation of leukoplakia 27. Therefore, early detection of leukoplakia is fundamental to finish their transformation into aggressive malignant OSCC, which could be hard to treat.
Proliferative verrucous leukoplakia (PVL)
PVL is a subversive course of oral leukoplakia that clinically presents equally multiple, slowly spreading white lesions with high reappearance rate and high probability of malignant transformation 28. A study of 47 patients diagnosed with PVL showed that around 40% of the patients adult malignant lesions (OSCC or verrucous carcinoma) during follow-upward (inside ii years) 29. Bagán et al. also reported in their study that there was a high occurrence of patients with PVL developing OSCC in different sites (gingiva and palate being most common) 30.
Erythroleukoplakia
Erythroleukoplakia (sometimes called speckled leukoplakia) is a mixed red and white lesion that virtually probable exhibits more advanced dysplastic changes in histopathological exam compared to leukoplakia 31. This lesion usually has irregular margins, and Candida colonization on these lesions is besides common 32. The chances of speckled leukoplakia for malignant transformation is eighteen–47% 33.
Erythroplakia
Defined equally "Any cherry-red lesion of the oral mucosa that cannot be clinically diagnosed equally any other status is called erythroplakia" 34. Truthful erythroplakia is a more alarming clinical finding compared to leukoplakia. nine A retrospective written report showed that 91% of 58 cases clinically observed as "erythroplakia" were diagnosed as OSCC (51%), carcinoma in situ or severe dysplasia (40%), or mild or moderate epithelial dysplasia (9%) 35. Erythroplakia and leukoplakia are unremarkably predecessors of OSCC 36 and sometimes besides seen side by side to an OSCC lesion 37.
Oral submucous fibrosis (OSMF)
OSMF occurs due to progressive fibrosis of the oral mucosa due to chronic use of areca nut 38. Patients diagnosed with OSMF are probable to develop malignant OSCC 39. A prospective study was carried out on 371 patients with microscopically proven diagnosis of OSCC and it was reported that around 30% of the patients (112) had a history of OSMF twoscore. Even so, a study carried out by Chourasia et al. reported an incidence of 4.2% for patients with OSMF transforming to OSCC 39.
Oral lichen planus (OLP)
An immune-mediated condition that clinically may present as reticular white areas that may or may not be associated with erosive and ulcerative lesions 41. There is however debate whether to consider OLP as a PMDs. A previous study in which the information of 20,095 patients was assessed reported 1.one% incidence of OLP patients developing OSCC 42. It should be noted however, that erosive type of OLP and patients with history of smoking and alcohol use are likely to suffer from transformation of OLP to OSCC 42, 43. It was reported in some other previous study that neoplasm recurrence charge per unit of OSCC is higher in patients who had previous OLP than the patients with main OSCC 44.
Common etiological factors of OSCC
Various etiological factors of OSCC have been reported in the literature. The near mutual are summarized below.
Cigarette smoking
Cigarette smoking helps in the spread of tumors by suppressing immunity and tumor suppressor genes, most importantly p53 and PTEN 45. In an earlier written report, al-Idrissi reviewed 65 patients with established diagnosis of caput and neck OSCC and reported that the bulk of these patients were men and 41.5% were smokers 46. In another report from China, which included 210 cases, a strong association between long term smoking and OSCC was reported 47. Llewelyn and Mitchell from Scotland reported in their report that out of 454 patients with confirmed oral cancer, threescore% were smokers and over 95% of those lesions were OSCC 48.
Alcohol consumption
A strong connection between drinking alcohol and several cancer types has been described in the literature 49. The synergetic effects of alcohol consumption and tobacco smoke increases the risk of OSCC past making the oral epithelium more permeable, dissolving tobacco, and promoting its penetration 50. However, chronic utilise of alcohol alone may pb to OSCC via several mechanisms, including DNA adduct formation, generation of ethanol-related reactive oxygen metabolites, and interference with the DNA-repair mechanism 51.
Shammah consumption
The consumption of shammah is on the rising in many countries 52. It is a combination of powdered smokeless tobacco with ingredients like lime, pepper, ash, and flavoring agents, and people use information technology by placing it in buccal cavity till the taste penetrates 53. In a previous written report from Jazan, Saudi Arabia, in which data from 132 patients were recorded, it was reported that the most common cancer detected was OSCC followed by thyroid cancer 52. Another report carried out on Yemeni shammah users ended that at that place was a potent association between daily shammah usage and formation of leukoplakia (a PMD) 54.
Chewing of khat
Khat is a establish that is mostly used for chewing and is a mixture of cathine and norephidrine 55. In a previous study, the prevalence of its consumption was establish to exist 23.ane% amongst university students of Jazan, Saudi Arabia 56. In an earlier case report of 1 patient, a strong affiliation between khat chewing and growth of OSCC was reported 57. Sawair et al. also reported a strong relationship betwixt khat chewing and evolution of OSCC in their study, which consisted of 649 Yemeni patients 58. Lukandu et al. reported from Kenya that chronic khat chewing could lead to abnormal epithelial thickening of oral mucosa and increased keratinization, and fibrosis 59.
Shisha (water pipe) smoking
Shisha is commonly available in restaurants, cafes, and other eatery shops in many countries and information technology contains a high concentration of nicotine, tar, and carbon monoxide sixty. In water piping smoking, smoke passes through h2o and there is a general idea that it is less harmful then cigarette smoking 61. In a recently published review, a strong association between h2o pipe smoking and head and neck cancers was reported 62. Zaid et al. reported in a written report from Syria and Lebanese republic that p53 gene mutations were associated water pipe smoking in OSCC 63. Al-Amad carried out a report in Jordan, which revealed that 36% of their sample who had oral cancer had a addiction of h2o pipe smoking 64.
Diagnosis of OSCC
Exfoliative cytology
Exfoliative cytology is a uncomplicated method that could prove useful in early identification of oral cancer as information technology is based on drove of exfoliated cells for microscopic examination 65. It should be noted however that cells tin suffer exfoliation normally and/or in the presence of a beneficial or malignant illness 66. Therefore, the nigh accurate diagnosis of OSCC should merely exist made by biopsy.
Biopsy
Despite the new diagnostic modalities in oral cancer detection, biopsy and histopathologic analysis remain the gold standard to diagnose OSCC 67. An adequate biopsy technique involves local anaesthesia assistants, having sufficient width and depth of the excised tissue, correct handling of the tissue, and submission without contamination to aid an accurate definitive diagnosis 68.
Role of salivary biomarkers in detection of OSCC
The typical diagnosis of OSCC is made by clinical oral examination followed by biopsy of the suspected tissue 69. Unfortunately, due to this arroyo, nigh OSCC cases either go undetected (at an early stage) or are diagnosed at advanced stages 70. In addition, due to belatedly diagnosis, metastasis for OSCC is very common, resulting in a five-year survival rate of less than 50% 71.
Human saliva could be used for the early detection of diverse diseases 72. OSCC is very common and its early detection tin meliorate the prognosis significantly 73. It has been suggested by various researchers that a specific group of protein biomarkers are increased in saliva of individuals with OSCC 74. Franzmann et al. reported CD44 every bit a probable biomarker of caput and neck cancer whereas, Nagler et al. described Cyfra-21-1 and cancer antigen-25 to exist potential biomarkers for oral cancer 74, 75. In an before study including 395 patients, Elashoff et al. stated an increment in expression of all seven transcriptomes and three proteins as possible markers for OSCC 76. They also reported an increase in the levels of IL-viii and subcutaneous adipose tissue in saliva exhibiting maximum levels of sensitivity and specificity to diagnose OSCC 77. Similarly, Arellano-Garcia et al. described that expression of IL8 and IL1β were increased in saliva of patients with OSCC as compared with command patients 78. Gleber-Netto et al. performed a report involving 180 patients and reported that among the proteomic markers, IL8 and IL1β concentration was greater in OSCC patients when compared with command and dysplasia patients 79. Awasthi performed a report that included 64 individuals with diagnosed cases of OSCC, pre-malignant conditions, and good for you controls 80. It was revealed from the results of that written report that patients with OSCC had increased salivary levels of Cyfra-21-one, lactate dehydrogenase, and total protein concentration in comparison to other groups eighty.
Conclusion
Our review concludes that OSCC has the potential for regional as well as distant metastasis. Many PMDs can transform into OSCC with the help of various etiological factors. Diagnosis of OSCC involves traditional biopsy, just salivary biomarkers could besides be utilized for its early diagnosis.
Data availability
No information is associated with this article.
Notes
[version 1; peer review: 3 approved]
Funding Argument
The writer(s) alleged that no grants were involved in supporting this piece of work.
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Reviewer response for version 1
Ali Leghari
1Department of Customs Dentistry, Baqai Dental College, Baqai Medical University, Karachi, Pakistan
The article is well written and I would like to accept it. I do accept the post-obit suggestions to improve its overall impact.
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In effigy 1: Addition of a clinical flick showing OSCC would benefit the article.
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It would be meliorate if PVL is mentioned as a distinct grade of oral leukoplakia and non as a subversive form.
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It would be amend if areca nut as a risk factor of OSCC also mentioned separately in heading "Common etiological gene of OSCC".
Is the review written in attainable language?
Yep
Are all factual statements correct and adequately supported by citations?
Yes
Are the conclusions drawn advisable in the context of the current inquiry literature?
Aye
Is the topic of the review discussed comprehensively in the context of the current literature?
Aye
Reviewer Expertise:
NA
I confirm that I have read this submission and believe that I accept an appropriate level of expertise to confirm that information technology is of an adequate scientific standard.
Reviewer response for version 1
Fatima Qadir
2Heart of clinical and diagnostic oral sciences, Establish of Dentistry, Barts & The London School of Medicine and Dentistry, Queen Mary University of London, London, Britain
Ambreen Rehman
1Queen Mary Academy of London, London, U.k.
The review on Oral squamous cell carcinoma is a well written comprehensive commodity. Information technology summarises the aetiology, metastasis and electric current diagnostic methods of OSCC. It also sheds light on possible use of salivary proteins to aid diagnosis. All the information provided is scientifically valid.
I would like the writer to review the following minor suggested changes:
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Recheck reference 1, I have not constitute any content related to the incidence of OSCC or Caput and neck cancer.
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Human Papilloma Virus (HPV) is one of the leading cause of OSCC. It should be included in the aetiology.
Is the review written in accessible language?
Yes
Are all factual statements correct and adequately supported by citations?
Yes
Are the conclusions fatigued appropriate in the context of the current research literature?
Yes
Is the topic of the review discussed comprehensively in the context of the current literature?
Yes
Reviewer Expertise:
Head and neck oral squamous cell carcinoma, micro-vesicles, Exosomes, oral cancer diagnostics.
We confirm that we accept read this submission and believe that we have an advisable level of expertise to confirm that it is of an acceptable scientific standard.
Reviewer response for version 1
Faisal Aljofi
1Section of Oncology and Diagnostic Sciences, Schoolhouse of Dentistry, University of Maryland, Baltimore, Md, USA
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In etiology section: it has been mentioned that in that location is a various etiological factors that cause OSCC, virtually of the articles that have been cited are based on epidemiological statistics. So I think it is amend to specify that these are based on epidemiological statistics.
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It has been mentioned that early detection of cancer using certain techniques like salivary bio markers will lead to successful prognosis and treatment, are there whatever studies showing that there is improved prognosis after early detection? If not so this would exist a good way to mention this as a proffer and time to come trend to plant studies to show the essential role of early diagnosis.
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Suggestions to add diagnostic criteria for early on detection of OSCC.
Is the review written in accessible language?
Yep
Are all factual statements correct and adequately supported past citations?
Aye
Are the conclusions fatigued appropriate in the context of the electric current inquiry literature?
Yes
Is the topic of the review discussed comprehensively in the context of the current literature?
Yeah
Reviewer Expertise:
NA
I ostend that I have read this submission and believe that I accept an appropriate level of expertise to confirm that it is of an adequate scientific standard.
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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194458/
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