Liquid Biopsy in Head and Neck Cancer: Its Present State and Future Role in Africa.

The rising mortality and morbidity rate of head and neck cancer (HNC) in Africa has been attributed to factors such as the poor state of health infrastructures, genetics, and late presentation resulting in the delayed diagnosis of these tumors. If well harnessed, emerging molecular and omics diagnostic technologies such as liquid biopsy can potentially play a major role in optimizing the management of HNC in Africa. However, to successfully apply liquid biopsy technology in the management of HNC in Africa, factors such as genetic, socioeconomic, environmental, and cultural acceptability of the technology must be given due consideration. This review outlines the role of circulating molecules such as tumor cells, tumor DNA, tumor RNA, proteins, and exosomes, in liquid biopsy technology for the management of HNC with a focus on studies conducted in Africa. The present state and the potential opportunities for the future use of liquid biopsy technology in the effective management of HNC in resource-limited settings such as Africa is further discussed.

Immune cells and associated molecular markers in dermal fibrosis with focus on raised cutaneous scars.

Raised dermal scars including hypertrophic, and keloid scars as well as scalp-associated fibrosing Folliculitis Keloidalis Nuchae (FKN) are a group of fibrotic raised dermal lesions that mostly occur following cutaneous injury. They are characterized by increased extracellular matrix (ECM) deposition, primarily excessive collagen type 1 production by hyperproliferative fibroblasts. The extent of ECM deposition is thought to be proportional to the severity of local skin inflammation leading to excessive fibrosis of the dermis. Due to a lack of suitable study models, therapy for raised dermal scars remains ill-defined. Immune cells and their associated markers have been strongly associated with dermal fibrosis. Therefore, modulation of the immune system and use of anti-inflammatory cytokines are of potential interest in the management of dermal fibrosis. In this review, we will discuss the importance of immune factors in the pathogenesis of raised dermal scarring. The aim here is to provide an up-to-date comprehensive review of the literature, from PubMed, Scopus, and other relevant search engines in order to describe the known immunological factors associated with raised dermal scarring. The importance of immune cells including mast cells, macrophages, lymphocytes, and relevant molecules such as cytokines, chemokines, and growth factors, antibodies, transcription factors, and other immune-associated molecules as well as tissue lymphoid aggregates identified within raised dermal scars will be presented. A growing body of evidence points to a shift from proinflammatory Th1 response to regulatory/anti-inflammatory Th2 response being associated with the development of fibrogenesis in raised dermal scarring. In summary, a better understanding of immune cells and associated molecular markers in dermal fibrosis will likely enable future development of potential immune-modulated therapeutic, diagnostic, and theranostic targets in raised dermal scarring.

The Practicality of the Use of Liquid Biopsy in Early Diagnosis and Treatment Monitoring of Oral Cancer in Resource-Limited Settings.

An important driving force for precision and individualized medicine is the provision of tailor-made care for patients on an individual basis, in accordance with best evidence practice. Liquid biopsy(LB) has emerged as a critical tool for the early diagnosis of cancer and for treatment monitoring, but its clinical utility for oral squamous cell carcinoma (OSCC) requires more research and validation. Hence, in this review, we have discussed the current applications of LB and the practicality of its routine use in Africa; the potential advantages of LB over the conventional "gold-standard" of tissue biopsy; and finally, practical considerations were discussed in three parts: pre-analytic, analytic processing, and the statistical quality and postprocessing phases. Although it is imperative to establish clinically validated and standardized working guidelines for various aspects of LB sample collection, processing, and analysis for optimal and reliable use, manpower and technological infrastructures may also be an important factor to consider for the routine clinical application of LB for OSCC. LB is poised as a non-invasive precision tool for personalized oral cancer medicine, particularly for OSCC in Africa, when fully embraced. The promising application of different LB approaches using various downstream analyses such as released circulating tumor cells (CTCs), cell free DNA (cfDNA), microRNA (miRNA), messenger RNA (mRNA), and salivary exosomes were discussed. A better understanding of the diagnostic and therapeutic biomarkers of OSCC, using LB applications, would significantly reduce the cost, provide an opportunity for prompt detection and early treatment, and a method to adequately monitor the effectiveness of the therapy for OSCC, which typically presents with ominous prognosis.

Deciphering the interaction of puerarin with cancer macromolecules: An in silico investigation.

The worldwide expanding increment in cancer pervasiveness is disturbing and this disease ranks among the main causes of mortality in both developing and developed countries. Unfortunately, available treatment options come with serious side effects and do not guarantee complete success. Although numerous models have been proposed for the development of better therapeutic agent, however the exact mechanism are still poorly understood. This then calls for continued research aimed at developing new drugs as an alternative or adjuvant anticancer agents. Here we have identified five vital proteins (CDK-2, Bcl-2, CDK-6, VEGFR, and IGF-1R) that aid tumor growth and we inhibited the activity of these proteins with Puerarin. Puerarin is an isoflavonoid C-glycosides used as a therapeutic agent against various human ailments. Our findings revealed that Puerarin fulfilled Veber's rule. Added to this, CDK-6 and Bcl-2 had better glide scores for puerarin than the control (doxorubicin) and molecular simulation showed the stability of the complexes. These findings suggest that inhibiting CDK-6 and Bcl-2 with Puerarin could prove more effective in the management of cancer than doxorubicin. Overall, this study provides a new direction that could facilitate rational drug design for cancer.Communicated by Ramaswamy H. Sarma.

The COVID-19 pandemic: the benefits and challenges it presents for medical education in Africa.

The coronavirus disease (COVID-19) has impacted many facets of everyday daily life, resulting in far-reaching consequences on social interaction, regional and global economies, and healthcare delivery systems. Numerous reports have commented on the impact of the COVID-19 pandemic on medical education in various world regions. However, we know little about the influence of the pandemic on medical education in Africa. Here, we discuss the potential impact of COVID-19 on teaching and learning in undergraduate medical education in sub-Saharan Africa, illustrating some of the unexpected benefits and challenges the pandemic presents for medical education in sub-Saharan Africa.

Targeted polymerase chain reaction-based expression of putative halitogenic bacteria and volatile sulphur compound analysis among halitosis patients at a tertiary hospital in Nigeria.

Halitosis (bad breath) can be a cause of anxiety, depression and psychosocial stress, with pathological changes in the oral microbiota playing an important role in its development. Despite its prevalence, studies on the microbiology of halitosis are rare in Nigeria. This study determines the presence of five putative periodontal pathogens viz: Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia and Treponema denticola on the tongue dorsa of halitosis and non-halitosis patients using a 16S rDNA-directed polymerase chain reaction assay. Furthermore, an association of these bacteria with oral malodour [as assessed by volatile sulphur compounds (VSC) measurements] with a portable sulphide monitor, the Halimeter (Interscan Corp, Chatsworth, California), was performed. The results showed that the prevalence of halitosis in this environment as defined by VSC level above 160 ppb is 14.9%. Halitosis is affected by gender with males having it more than the females. Males also tend to present more with self-reported complaints of halitosis than females. Age does not appear to contribute to the incidence of halitosis. Fusobacterium nucleatum, P. gingivalis, P. intermedia are responsible for increased production of VSCs in halitosis patients while A. actinomycetemcomitans and T. denticola appear to play no part in the production of VSCs. Evaluation of halitogenic bacteria and VSCs may potentially become a surrogate biomarker for monitoring halitosis. Targeted assessment of putative halitogenic bacteria may provide a rapid point-of-care diagnostic tool for halitosis.

Reliability of Histopathology for the Early Recognition of Fibrosis in Traction Alopecia: Correlation with Clinical Severity.

Traction alopecia (TA) is hair loss caused by prolonged pulling or repetitive tension on scalp hair; it belongs to the biphasic group of primary alopecia. It is non-scarring, typically with preservation of follicular stem cells and the potential for regrowth of early lesions especially if traction hairstyles are stopped. However, the alopecia may become permanent (scarring) and fail to respond to treatment if the traction is excessive and prolonged. Hence, the ability to detect fibrosis early in these lesions could predict patients who respond to treatment. Histopathological diagnosis based on scalp biopsies has been used as a gold standard to delineate various forms of non-scarring alopecia and to differentiate them from scarring ones. However, due to potential discrepant reporting as a result of the type of biopsy, method of sectioning, and site of biopsy, histopathology often tends to be unreliable for the early recognition of fibrosis in TA. In this study, 45 patients were assessed using the marginal TA severity scoring system, and their biopsies (both longitudinal and transverse sections) were systematically assessed by three dermatopathologists, the aim being to correlate histopathological findings with clinical staging. Intraclass correlation coefficients were used to determine the level of agreement between the assessors. We found poor agreement of the identification and grading of perifollicular and interfollicular fibrosis (0.55 [0.23-0.75] and 0.01 [2.20-0.41], respectively), and no correlation could be drawn with the clinical severity score. Better methods of diagnosis are needed for grading and for recognition of early fibrosis in TA.

The Prospect and Challenges to the Flow of Liquid Biopsy in Africa.

Liquid biopsy technologies have the potential to transform cancer patient management as it offers non-invasive diagnosis and real-time monitoring of disease progression and treatment responses. The use of liquid biopsy for non-invasive cancer diagnosis can have pivotal importance for the African continent where access to medical infrastructures is limited, as it eliminates the need for surgical biopsies. To apply liquid biopsy technologies in the African setting, the influence of environmental and population genetic factors must be known. In this review, we discuss the use of circulating tumor cells, cell-free nucleic acids, extracellular vesicles, protein, and other biomolecules in liquid biopsy technology for cancer management with special focus on African studies. We discussed the prospect, barriers, and other aspects that pose challenges to the use of liquid biopsy in the African continent.

A multi-centre evaluation of malignant odontogenic tumours in Nigeria.

INTRODUCTION: odontogenic tumors originate from neoplastic transformation of the remnants of tooth forming apparatus. There are varying degrees of inductive interactions between odontogenic ectomesenchyme and epithelium during odontogenesis, leading to lesions that vary from benign to malignant. Malignant odontogenic tumours (MOTs) are very rare and are classified according to embryonic tissue of origin. Recently, there has been a few changes to the classification of MOTs according to the World Health Organization's (WHO) classification in 2017. This study aims to evaluate and reclassify MOTs, using a multi-centre approach in some major tertiary dental hospitals in Nigeria. METHODS: this study reviewed the clinicopathological data on 63 cases of MOT diagnosed over 25 years in five major tertiary dental hospitals in Nigeria. All MOT cases were reclassified according to the recent revision to the 2017 WHO classification of odontogenic tumours. RESULTS: from a total of 10,446 biopsies of oral and jaw lesions seen at the 5 study centres over the 25-year study period, 2199 (21.05%) cases were found to be odontogenic tumours (OTs), of which 63 were MOT. MOTs constituted 0.60% of the total biopsy cases and 2.86% of OTs. Odontogenic carcinomas presented with a mean age higher than odontogenic sarcomas. According to our 2017 WHO reclassification of MOTs, odontogenic carcinomas, ameloblastic carcinomas and primary intraosseous carcinomas were found to be the top three lesions, respectively. Carcinosarcomas were found to be extremely rare. CONCLUSION: using a multi-centre approach is a robust way to reduce diagnostic challenges associated with rare maxillofacial lesions such as MOTs.

Applications of SNAP-tag technology in skin cancer therapy.

BACKGROUND: Cancer treatment in the 21st century has seen immense advances in optical imaging and immunotherapy. Significant progress has been made in the bioengineering and production of immunoconjugates to achieve the goal of specifically targeting tumors. DISCUSSION: In the 21st century, antibody drug conjugates (ADCs) have been the focus of immunotherapeutic strategies in cancer. ADCs combine the unique targeting of monoclonal antibodies (mAbs) with the cancer killing ability of cytotoxic drugs. However, due to random conjugation methods of drug to antibody, ADCs are associated with poor antigen specificity and low cytotoxicity, resulting in a drug to antibody ratio (DAR) >1. This means that the cytotoxic drugs in ADCs are conjugated randomly to antibodies, by cysteine or lysine residues. This generates heterogeneous ADC populations with 0 to 8 drugs per an antibody, each with distinct pharmacokinetic, efficacy, and toxicity properties. Additionally, heterogeneity is created not only by different antibody to ligand ratios but also by different sites of conjugation. Hence, much effort has been made to find and establish antibody conjugation strategies that enable us to better control stoichiometry and site-specificity. This includes utilizing protein self-labeling tags as fusion partners to the original protein. Site-specific conjugation is a significant characteristic of these engineered proteins. SNAP-tag is one such engineered self-labeling protein tag shown to have promising potential in cancer treatment. The SNAP-tag is fused to an antibody of choice and covalently reacts specifically in a 1:1 ratio with benzylguanine (BG) substrates, eg, fluorophores or photosensitizers, to target skin cancer. This makes SNAP-tag a versatile technique in optical imaging and photoimmunotherapy of skin cancer. CONCLUSION: SNAP-tag technology has the potential to contribute greatly to a broad range of molecular oncological applications because it combines efficacious tumor targeting, minimized local and systemic toxicity, and noninvasive assessment of diagnostic/prognostic molecular biomarkers of cancer.

Concordance between clinical and histopathologic diagnosis and an audit of oral histopathology service at a Nigerian tertiary hospital.

INTRODUCTION: Although histopathological diagnosis remains the gold standard; good clinical impression is potentially a key diagnostic tool in rural resource-limited settings. Thus, good concordance between clinical impression and histopathological diagnosis is thus a very crucial diagnostic oral pathology tool in low- and middle-income countries (LMICs). METHODS: This retrospective study was performed at the Oral pathology and Oral diagnoses units of Obafemi Awolowo University Teaching Hospital Complex (OAUTHC), Osun state. Clinicopathological reports of all biopsies between the period of 2008-2017 were retrieved and analyzed. Descriptive analysis of data was done using Stata 14. Frequency of oral lesions and rates of accurate clinical diagnoses were evaluated for lesional sites and clinician's qualification/specialization. RESULTS: In 592 biopsied cases, the mean age was 36.1years with higher female predilection (54.4%). Odontogenic tumors (OTs) were the most prevalent category of lesions (25.3%, n=149), followed by reactive lesions (12%, n=71). Absolute concordance was recorded for 54.6% (k=0.5) of the cases; with highest concordance observed in fibro-osseous lesions (65.6%, k=0.43), and least in pulp/periapical lesions (3.5%). Concordance was higher in females (59.5%, k=0.53) than males (48.3%, k=0.44). Oral medicine specialists had the highest concordance index (62.5%, k=0.59). CONCLUSION: The findings in this research indicate that, on a general note, the degree of concordance between clinical and histopathological diagnosis is poor. Hence, improvement in diagnostic skills (irrespective of clinical specialty) is important to improve treatment outcomes, particularly in LMICs. Continuous personnel training and utilization of advanced diagnostic techniques can potentially help bridge the diagnostic gaps.

Descriptive epidemiology of salivary gland neoplasms in Nigeria: An AOPRC multicenter tertiary hospital study.

OBJECTIVES: Accurate diagnosis of salivary gland neoplasms (SGN) in many centers in Africa is limited by poor diagnostic resources and ancillary services. Hence, we have carried out a multicenter epidemiological study to understand the true burden of SGN in Nigeria. METHOD: In this descriptive cross-sectional study, we have deployed resources available to members of the African Oral Pathology Consortium (AOPRC) to examine the burden of salivary gland lesions in Nigeria, using a multicenter approach. Data from seven major tertiary health institutions in northern, western, and southern Nigeria were generated using a standardized data extraction format and analyzed using the Epi-info software (Version 7.0, Atlanta, USA). RESULT: Of the 497 cases examined across the seven centers, we observed that SGN occurred more in females than males. Overall, pleomorphic salivary adenoma (PA) was found to be the most common. PA was found to be the commonest benign SGN while adenocystic carcinoma (ADCC) was the commonest malignant SGN. Regional variations were observed for age group, diagnosis, and gender distribution. Significant statistical differences were found between males and females for malignant SGNs (p-value=0.037). CONCLUSION: We found regional variation in the pattern of distribution of SGN in Nigeria. This is the largest multicenter study of SGN in Nigeria, and our findings are robust and representative of the epidemiology of this neoplasm in Nigeria.

The dentist-scientist career pathway in Africa: opportunities and obstacles.

The future of evidence-based dentistry in developing Africa heavily depends on a sustainable establishment of a vibrant dentist-scientist workforce. A dentist scientist is saddled with the responsibility of carrying out robust cutting edge research projects that are inspired by clinical experience. Currently, there are no pipelines in place to systematically train such dentists, neither are there programs in place to allow trained African dentists choose such a career pathway. A dentist-scientist is a person who studied oral, dental, maxillofacial (or craniofacial) diseases, prevention, and population sciences (obtaining a medical degrees such as bachelor of dental surgery [BDS] or BChD) alone; or in combination with other advanced degrees such as doctor of dental surgery (DDS)/doctor of philosophy (PhD) or BDS/PhD. This situation has resulted in overdependence of African clinical practice on research findings from technologically advanced Western countries and a decline in clinical research capacity building. The career path of a dentist-scientist should involve research along the spectrum of basic biomedical sciences, translational, clinical and public health sciences. There are several factors responsible for the ultra-low count of dentist-scientist in the heterogeneous African communities such as: poor biomedical research infrastructure; lack of funding; absence of structured dentist scientist career pathways; lack of personnel, inter alia. Hence, this review hopes to discuss the opportunities of setting up a dentist-scientist training pathway in Africa (as obtains in most developed world settings), identify opportunities and prospects of developing an African dentist-scientist workforce, and finally discuss the challenges involved.

The physician-scientists: rare species in Africa.

There is paucity of physician-scientists in Africa, resulting in overt dependence of clinical practice on research findings from advanced "first world" countries. Physician-scientists include individuals with a medical degree alone or combined with other advanced degrees (e.g. MD/MBChB and PhD) with a career path in biomedical/ translational and patient-oriented/evaluative science research. The paucity of clinically trained research scientists in Africa could result in dire consequences as exemplified in the recent Ebola virus epidemic in West Africa, where shortage of skilled clinical scientists, played a major role in disease progression and mortality. Here we contextualise the role of physician-scientist in health care management, highlight factors limiting the training of physician-scientist in Africa and proffer implementable recommendations to address these factors.

Ameloblastic carcinoma: a clinicopathologic analysis of cases seen in a Nigerian Teaching Hospital and review of literature.

INTRODUCTION: Ameloblastic carcinoma is a rare malignant odontogenic neoplasm that exhibits histological features of ameloblastoma in combination with cytological atypia. It may arise de novo or secondarily through malignant de-differentiation of pre-existing ameloblastoma or odontogenic cyst. Secondary ameloblastic carcinomas often results from repeated surgical intervention, which is a mainstay of odontogenic tumor management in resource limited settings. To date, relatively few cases of ameloblastic carcinomas have been reported and many cases have been misdiagnosed as ameloblastoma. This is due to its wide range of clinicopathological feature which range from indolent to aggressive. It may present as an aggressive ulcerated mass or as a simple cystic lesion; hence, it often challenging to delineate from its benign counterpart, ameloblastoma. METHODS: this study reviewed the clinicopathological data on 157 cases of odontogenic tumors diagnosed over a 10 years period from the pathology archive of the Oral Pathology Unit of Obafemi Awolowo University Teaching Hospital Complex (OAUTHC), Ile-Ife, Nigeria. RESULTS: of all these cases, we identified that 64.9% were Ameloblastomas, while 8.3% were ameloblastic carcinomas. Primary subtypes of ameloblastic carcinoma constituted 23.08%, while 69.23% of the cases were of the secondary subtype. We also found that the secondary subtype of ameloblastic carcinomas showed a higher mean duration value of 7.7 years. Most lesions were found in posterior mandible and presented with ulceration, perforation and ill-defined borders radiographically. CONCLUSION: this study is among the few that have documented higher frequency of secondary ameloblastic carcinoma in the scientific literature.

A multi-centre evaluation of oral cancer in Southern and Western Nigeria: an African oral pathology research consortium initiative.

INTRODUCTION: Oral cancer is a leading cause of cancer deaths among African populations. Lack of standard cancer registries and under-reporting has inaccurately depicted its magnitude in Nigeria. Development of multi-centre collaborative oral pathology networks such as the African Oral Pathology Research Consortium (AOPRC) facilitates skill and expertise exchange and fosters a robust and systematic investigation of oral diseases across Africa. METHODS: In this descriptive cross-sectional study, we have leveraged the auspices of the AOPRC to examine the burden of oral cancer in Nigeria, using a multi-centre approach. Data from 4 major tertiary health institutions in Western and Southern Nigeria was generated using a standardized data extraction format and analysed using the SPSS data analysis software (version 20.0; SPSS Inc. Chicago, IL). RESULTS: Of the 162 cases examined across the 4 centres, we observed that oral squamous cell carcinomas (OSCC) occurred mostly in the 6th and 7th decades of life and maxillary were more frequent than mandibular OSCC lesions. Regional variations were observed both for location, age group and gender distribution. Significant regional differences was found between poorly, moderately and well differentiated OSCC (p value = 0.0071). CONCLUSION: A multi-centre collaborative oral pathology research approach is an effective way to achieve better insight into the patterns and distribution of various oral diseases in men of African descent. The wider outlook for AOPRC is to employ similar approaches to drive intensive oral pathology research targeted at addressing the current morbidity and mortality of various oral diseases across Africa.