Precancerous Disorders Research Articles

Assessments of the Quality, Understandability, and Actionability of Arabic Web-Based Content on Oral Cancer and Precancerous Disorders

Plain Language SummaryPatients with mouth skin changes, that raise the risk of mouth cancer, may search the net to find information to help them care for themselves and to ask for help – if they think a doctor visit will benefit them. There are good reading sources for Arabic health information about mouth health, but they are usually short and not enough. Also, the language can be difficult to understand and remember. To solve this, health professionals must create information about mouth diseases and make it available online to supplement what they have received during the clinical visits.

Histomorphometric analysis of angiogenesis in oral submucous fibrosis and oral squamous cell carcinoma associated with oral submucous fibrosis

Background: Oral submucous fibrosis (OSMF), now worldwide acknowledged as the disease of “Southeast Asia and Indian subcontinent”, has the utmost malignant transformation prevalence amongst oral precancerous disorders. Increased vascularity that is neoangiogenesis has been observed in the superficial connective tissue region of pre-cancerous lesions showing dysplasia. This could be an initial occurrence of the carcinogenesis process. The aim of this study will be to analyse neoangiogenesis by examining immunoexpression of CD105 in OSMF, and OSCC with OSMF cases. Methods: The project will comprise 30 normal oral mucosa samples (group I), 30 clinicopathologically diagnosed cases of OSMF (group II), and on the basis of association of OSMF, 30 surgically operated and histopathologically diagnosed cases of OSCC associated with OSMF (group III). Hematoxylin and eosin stains will be used for routine staining procedures and immunohistochemistry for the expression of CD105. Oral epithelial dysplasia (OED) cases of OSMF will be categorized into two groups, low-risk epithelial dysplasia (LRED) and high-risk epithelial dysplasia (HRED). The micro vessel density (MVD), total microvessel area (TVA), and mean microvessel area (MVA) are within and surrounding the tumor tissue sections immunostained with the CD105 antibody will be determined. ANOVA will be applied for evaluation of the mean scores of MVD, TVA, and MVA of groups II and III. The obtained score will be compared with different parameters of OSCC (TNM stage, lymph node metastasis, and histopathological grades). Conclusions: We postulate the progressively increased vascularity with the disease progression from LRED to HRED and further its transformation to invasive oral squamous cell carcinoma This increased vascularity will be evident by enhanced MVD, TVA and mean MVA, which is expressed by CD105 immunoexpression. This observation will emphasize the significance of neoangiogenesis in cases of OSMF with epithelial dysplasia and its further progression to OSCC.

A Survey on Parents' Health Literacy on Childhood Human Papilloma Virus Vaccination

Abstract Objective The aim of this study is to determine parents' knowledge levels and attitudes about childhood human papillomavirus (HPV) vaccination and reveal the differences between parents who are health care workers and nonhealth care workers. The HPV vaccine can potentially prevent initial HPV infection and HPV-related genital and anal precancerous disorders and cancers. Methods Questions and attitudes toward childhood HPV vaccination were asked to 564 parents who agreed to participate in the study. Results In our study, the rate of health care worker parents considering having their children vaccinated against HPV (63.1%) was higher than that of nonhealth care worker parents (11.4%). Only 5% of parents had their children previously vaccinated against HPV; however, there was no difference between parents who were health care workers and those who were not. In addition, this rate was relatively low compared to other paid vaccines (49.8, 35.3, and 18.8%, respectively). Parents who had not previously vaccinated their children against HPV were considering getting their children vaccinated, especially if a pediatrician recommended it. Conclusion The parents' high level of health literacy may not be effective in deciding to vaccinate their children against HPV. Therefore, adequate information and awareness should be provided to all parents about HPV vaccination as early as possible for all children of appropriate age. Pediatricians should be given important roles in raising the awareness of parents about childhood HPV vaccination by health authorities.

Soft Palate Variation in Oral Submucous Fibrosis

One among the most prevalent precancerous disorders affecting oral cavity in those who consume arecanut and gutka is oral submucous fibrosis (OSMF). The anatomy of the soft palate alters as this illness proceeds and can act as a marker for disease. OSMF prevalence varies by area and ethnicity, and is closely linked to behaviours, culture, and cuisine. People in South and Southeast Asia have the greatest frequency of OSMF.OSMF has afflicted 2.5 million individuals globally, with a total of five million in the Indian individuals. The percentage of OSMF patients with dysplasia might range from 12 to 15 percent. Malignant changes occurs at a rate of 4–13 percent around world, but 7.6 percent in the Indian subcontinent. The anatomy of the soft palate in OSMF patients has been studied in a number of ways. Cephalometric analysis is highly used methods for measuring the soft palate in both healthy and OSMF patient. On lateral cephalometry, the soft palate shows a variety of radiographic appearances. Early cephalometry diagnosis of OSMF plays a vital role in treatment of disease. Soft palate becomes thick and heavy as OSMF advances, and considerable changes in soft palate dimensions occur, which may be better assessed by CBCT. This review work compared studies from several researchers, and observed that Type 1soft palate is the most prevalent, while type 6 soft palate is the least common.

Abstract LB102: Effect of mistletoe extract on growth and proliferation of prostate cancer cells

Abstract Complementary and alternative medicines are explored for their role in improving the quality of life of patients with cancer. Many anti-cancer drugs have been derived from natural sources. Mistletoe extract, composed of lectins, viscotoxins, flavonoids, and other biologically active substances, has two mechanisms of action: tumor cytotoxicity and immunomodulation. The cytotoxic effects of mistletoe extract are a result of protein synthesis interference, cell cycle inhibition, and apoptosis induction. Further, mistletoe extract has been shown to have anti-angiogenic properties. In Europe, Helixor M, mistletoe extract from Viscum album mali, is used as an anthroposophic medicine in the treatment of malignant and non-malignant tumors, malignant disorders with accompanying impairment of the hematopoietic organs, stimulation of bone marrow activity, reducing the risk of tumor recurrence, and diagnosed pre-cancerous disorders. However, only limited evaluation of mistletoe extract has been conducted in the United States. We studied the effects of Helixor M in prostate cancer. To evaluate its effect on cell proliferation and survival, we treated androgen receptor (AR) positive (LNCaP, LAPC4 and VCaP) and AR negative (PC3 and DU-145) cell lines with Helixor M. Our data indicates that LNCaP and LAPC4 cells were most sensitive to Helixor M while PC3, DU-145, and VCaP cells were relatively resistant to treatment. While AR protein levels and NF-kappaB subunits remained unaffected by treatment, there was an induction of apoptosis along with a concomitant decrease in LC3B, an autophagy marker, in all the sensitive prostate cancer cell lines. In search of pathways that may synergize with growth inhibition by Helixor M, we utilized CRISPR knockouts of TBK1, a kinase involved in autophagy induction, in LNCaP cells and tested whether TBK1 knockouts are synthetically lethal with Helixor M. Helixor M induced increased apoptosis in TBK1 knockouts as compared to parental LNCaP cells, indicating that TBK1 loss might be synthetically lethal with Helixor M. Citation Format: Kavya Boyapati, Rajendra Kumar, Lillian Wilson, Yuhan Yang, Deven Topiwala, Keerti Soundappan, Eleni Panagopoulos, Ivelisse Page, Jennifer Durham, Michael Carducci, Channing Paller, Sushant Kachhap. Effect of mistletoe extract on growth and proliferation of prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB102.

A comparative study to assess the independency of lipid profile and blood sugar levels as a diagnostic marker in oral cancer and precancerous disorders

Context: Lipids are the main cell membrane components important for different biological functions including cell growth and division of normal and malignant tissues. Low lipid values in cancer, precancer lesion, and condition may be due to of lipid peroxidation and also lipids play a key role in the higher utilization of lipids including total cholesterol (TC) and triglycerides (TG) for new membrane biogenesis. Aims: The present study was aimed to assess the independency and comparison of serum lipid profile and blood glucose level in patients with oral carcinoma and precancerous lesions and conditions. Settings and Design: The total sample sizes of 180 individuals were chosen in a 2-year duration: 60 were diagnosed with leukoplakia/oral submucous fibrosis, 60 with oral carcinoma, and 60 of the control group. Subjects and Methods: The serum triglycerides (TGs) were estimated by GPO-PAP End Point Assay method, total cholesterol (TC) by CHOD-PAP, and high-density lipoprotein (HDL) cholesterol by PEG-CHOD-PAP End Point Assay method with lipid clearing factors. The low-density lipoprotein (LDL) and very LDL (VLDL) levels were calculated using Friedewald's equation. Statistical Analysis Used: Collected data were statistically calculated by Student's t-test and by Chi-square test with SPSS version 17. All values were considered statistically significant for a value of P

Biochemical role of phytoestrogen (Chrysin) against N-methyl nitrosourea (NMU)- induced proliferative lesions in mammary glands of postmenopausal female rat

This study aimed to investigate the role of the phytoestrogen (chrysin) in the treatment or protection of NMU-induced preneoplastic lesions in mammary glands of postmenopausal female rats. Rats (n=105) were divided into seven groups (n=15/group); group1(negative control group).Groups 2&3 (positive control groups), rats were injected intraperitoneally (i.p.) with 4 doses of NMU (75 mg/kg b.w.,once/5days) before or after oral administration of glycofurol. Groups 4 &5(treatment groups),rats received 4 doses of NMU (75 mg/kg b.w., once/5days,i. p.), left for 6 weeks then followed by 3 doses, per week, of chrysin (125 or 250 mg/kg b.w., orally; p.o), respectively, for another 6 weeks. Groups 6 & 7(protective groups), rats received 3 doses, per week, of chrysin(125 or 250 mg/kg b.w.,p.o.), for 6 weeks then followed by 4 doses of NMU (75 mg/kg b.w., once/5days, i.p.) then left for another 6 weeks. The NMU injection caused significant decrease in PLT count, lymphocytes %, Hb, MCH, MCHC, E2, TAC levels as well as GST and CAT activities. The results also showed that NMU significantly elevated WBC count, granulocytes%, monocytes %, MCV, RDW%, CRP, CEA levels and arginase activity. Either treatment or protection with chrysin modulated the adverse effects of NMU and ameliorated the change in the biochemical parameters. The biochemical observations were also confirmed by histological studies. In conclusion, phytoestrogens may relieve the severity of postmenopausal pre-cancerous disorders, especially when consumed in high dose for a while before the incidence of lesions.

Addressing overdiagnosis and overtreatment in cancer: a prescription for change

A vast range of disorders--from indolent to fast-growing lesions--are labelled as cancer. Therefore, we believe that several changes should be made to the approach to cancer screening and care, such as use of new terminology for indolent and precancerous disorders. We propose the term indolent lesion of epithelial origin, or IDLE, for those lesions (currently labelled as cancers) and their precursors that are unlikely to cause harm if they are left untreated. Furthermore, precursors of cancer or high-risk disorders should not have the term cancer in them. The rationale for this change in approach is that indolent lesions with low malignant potential are common, and screening brings indolent lesions and their precursors to clinical attention, which leads to overdiagnosis and, if unrecognised, possible overtreatment. To minimise that potential, new strategies should be adopted to better define and manage IDLEs. Screening guidelines should be revised to lower the chance of detection of minimal-risk IDLEs and inconsequential cancers with the same energy traditionally used to increase the sensitivity of screening tests. Changing the terminology for some of the lesions currently referred to as cancer will allow physicians to shift medicolegal notions and perceived risk to reflect the evolving understanding of biology, be more judicious about when a biopsy should be done, and organise studies and registries that offer observation or less invasive approaches for indolent disease. Emphasis on avoidance of harm while assuring benefit will improve screening and treatment of patients and will be equally effective in the prevention of death from cancer.

PD1. Premalignant lesions

Oral cancer appears to be increasing in incidence, and mortality has scarcely improved over past decades. Better understanding of aetiopathogenesis should lead to more accurate and earlier diagnosis and more effective treatments with fewer adverse effects, providing the best chance of a cure. Cancer is the result of DNA mutations arising spontaneously and from the action of various mutagens, especially in tobacco and alcohol. Cancer is a consequence of an interaction of many factors. A sequence of genetic changes leads eventually to loss of growth control and autonomy, but countering these changes are mechanisms to metabolise carcinogens, repair DNA damage, control growth, and defend against cancer. Potentially malignant (premalignant or precancerous) disorders which precede some neoplasms include erythroplasia (erythroplakia) – the most likely lesion to progress to severe dysplasia or carcinoma, leukoplakia, lichen planus and submucous fibrosis. Risk factors include tobacco, betel and alcohol use. Clinical features which suggest a potentially malignant lesion is likely to transform, or has transformed, to carcinoma include: the presence of red lesions (erythroplasia); a verrucous, speckled or granular appearance or an ulcer with fissuring or raised exophytic margins; induration; fixation of the lesion to deeper tissues or to overlying skin or mucosa; cervical lymph node enlargement. Single ulcers, lumps, red patches, or white patches – particularly if any of these are persisting for more than three weeks, may be manifestations of frank malignancy. There should be a high index of suspicion, especially of a solitary lesion present for over 3 weeks: biopsy is invariably indicated. The whole oral mucosa should be examined as there may be widespread dysplastic mucosa (‘‘field change’’) or even a second neoplasm and the cervical lymph nodes must always be examined. Laboratory diagnostic aids increasingly look to detect cellular and now molecular changes. Molecular techniques are being introduced for prognostication.

Correlation of Trace Elemental Profiles in Blood Samples of Indian Patients with Leukoplakia and Oral Submucous Fibrosis

In order to ascertain possible correlation between alterations in trace elemental profile and the progression or regression of two most common potentially malignant disorders affecting oral cavity, namely oral submucous fibrosis and leukoplakia, blood from 60 patients from each group of patients as well from 30 healthy individuals was analyzed for elemental profiling employing EDXRF technique. Out of the 16 detected elements (K, Si, Ca, V, Cr, Ni, Mn, Fe, Cu, Zn, Se, Br, Rb, Sr, Co, and Pb), Mn, Fe, Zn, Br, and Co showed remarkable alteration in their profile in both leukoplakia and oral submucous fibrosis patients with respect to the normal healthy individuals. While Zn, Br, and Fe reflected similar changes--showing gross depletion in both the diseased groups, Mn and Co depicted inverse pattern of alterations in their concentrations in the two types of precancerous disorders when compared to the control subjects.

3.03] Optical coherence tomography as a non-invasive imaging technique for examination of cervical tissue

Objective Optical coherence tomography (OCT) is a non-invasive high-resolution real-time imaging technique that permits delineation of features up to 2 mm in depth. The purpose of this study was to examine the capabilities of OCT in characterizing cancerous and precancerous lesions of the uterine cervix. Patients and methods We conducted a single-institution, review board-approved, prospective study on the use of OCT as an adjunct to standard colposcopy and biopsy in 25 women with suspected cervical intraepithelial neoplasia (CIN). OCT images of suspicious areas were obtained before biopsy, interpreted in real time and subsequently compared with the corresponding histology. Results We obtained 47 images with corresponding histology in 25 women undergoing colposcopy for suspected CIN. In total 35 of the 37 histologically proven CIN lesions were diagnosed correctly by OCT with a sensitivity of 95%. Five of ten biopsy sites with histologically no dysplasia were misinterpreted by OCT thereby suggesting CIN. However, there were inflammatory changes in 3 of these specimens which were possibly the cause of the misinterpretations and the low specificity of 50%. Conclusion OCT is a rapid, easy-to-use modality that provides real-time microarchitectural information. With further experience we expect to overcome the present difficulties in distinguishing between early precancerous lesions and inflammatory disorders. On the basis of the above findings, we believe that this technology has the potential to improve the management of cervical dysplasia.

P158 Consequences of Chewing Habits in Gujarat, India

Objective: To investigate the effect of chewing areca and/or betel quid with pan masala (tobacco) on oral hard tissue, oral submucous fibrosis (OSMF), and associated molecular impairment underlying the causation of oral precancerous disorders.

Neopterin as an indicator of immune activation and prognosis in patients with gynecological malignancies

Malignant tumors may contribute to host response that involves both the adaptive and innate immune systems. Among other biochemical indicators of systemic immune and inflammatory activity, activation of macrophages by interferon-gamma induces a marked increase in the production of neopterin. Neopterin production by activated macrophages is also associated with tryptophan degradation. In addition to tumors of other primary locations, increased urinary and serum neopterin concentrations have been reported in patients with gynecological cancers, including epithelial ovarian carcinoma, cervical carcinoma, endometrial carcinoma, uterine sarcomas, and vulvar carcinoma, but not in women with benign neoplasms or precancerous disorders. Increased neopterin concentrations have been associated with poor prognosis. Elevated levels of neopterin have also been observed in the tumor microenvironment. Systemic (urinary or serum) or local (ascitic fluid) neopterin concentrations increased after therapeutic administration of cytokines. Elevated neopterin concentrations have been associated with anemia of chronic disease and increased urinary zinc loss in patients with gynecological malignancy. Elevated neopterin has also been connected with depressed function of peripheral blood lymphocytes and a decrease in CD4+ T-cell numbers.

Neopterin as an indicator of immune activation and prognosis in patients with gynecological malignancies

Malignant tumors may contribute to host response that involves both the adaptive and innate immune systems. Among other biochemical indicators of systemic immune and inflammatory activity, activation of macrophages by interferon-γ induces a marked increase in the production of neopterin. Neopterin production by activated macrophages is also associated with tryptophan degradation. In addition to tumors of other primary locations, increased urinary and serum neopterin concentrations have been reported in patients with gynecological cancers, including epithelial ovarian carcinoma, cervical carcinoma, endometrial carcinoma, uterine sarcomas, and vulvar carcinoma, but not in women with benign neoplasms or precancerous disorders. Increased neopterin concentrations have been associated with poor prognosis. Elevated levels of neopterin have also been observed in the tumor microenvironment. Systemic (urinary or serum) or local (ascitic fluid) neopterin concentrations increased after therapeutic administration of cytokines. Elevated neopterin concentrations have been associated with anemia of chronic disease and increased urinary zinc loss in patients with gynecological malignancy. Elevated neopterin has also been connected with depressed function of peripheral blood lymphocytes and a decrease in CD4+T-cell numbers.

Oral precancerous disorders associated with areca quid chewing, smoking, and alcohol drinking in southern Taiwan

To investigate the prevalence and the associated risk factors of oral precancerous disorders in southern Taiwan. We conducted a cross-sectional community survey interviewing 1075 adult subjects, 15 years of age and over, gathered from randomly selected 591 households, and spanning five villages in southern Taiwan. The study protocol included a visual oral soft tissue examination and a questionnaire-based interview. The chi-square test was used to test the differences in prevalence of oral precancerous lesions and conditions by different "life styles" relating to current risk habits of current areca quid chewing, smoking, and alcohol drinking. To control for possible confounding, a logistic regression model was used to estimate the Odds Ratios (OR) for leukoplakia and oral submucous fibrosis (OSF). 136 precancerous lesions and conditions were detected among 1075 subjects (12.7%). The analysis of the spectrum of oral precancerous disorders detected, leukoplakia (n = 80), OSF (n = 17) and verrucous lesions (n = 9), demonstrated an association with gender (P < 0.001). There were statistically significant associations among leukoplakia (P < 0.01), OSF (P < 0.0001), and verrucous lesions (P < 0.0001) and the life style of current areca quid chewing, smoking, and alcohol drinking. The synergistic effect of smoking and areca quid chewing habit on leukoplakia and OSF was demonstrated. This study reinforces the association of current areca quid chewing without tobacco, cigarette smoking, and alcohol drinking to leukoplakia, OSF, and verrucous lesions in Taiwan.

Topical intralesional treatment with ʼIntron Aʼ|Sr in basal cell carcinoma precancerous skin disorders and early skin cancer

Topical intralesional treatment with ʼIntron Aʼ|Sr in basal cell carcinoma precancerous skin disorders and early skin cancer

Cholesterol oxides and carcinogenesis

Experimental evidence indicates a relationship between cholesterol alpha-epoxide and skin cancer, and exposure of skin fibroblasts to ultraviolet radiation enduces formation of significant levels of this oxide. Colon cancer is also etiologically linked to cholesterol oxidation products. Higher than normal levels of cholestanetriol have been found in patients with colon cancer and also in those with precancerous disorders such as adenomatous polyps and ulcerative colitis. Higher than normal levels of cholesterol alpha-epoxide have been found in breast fluid aspirates of women with benign breast disease, with or without atypical hyperplasia of the epithelium, and this may be a factor in the increased incidence of breast cancer associated with hyperplasia. Similarly, the observed increased levels of cholesterol alpha and beta-epoxides in prostatic fluid of men with benign prostatic hypertrophy may be associated with subsequent development of prostate cancer. Cholesterol alpha-epoxide has been found to be mutagenic to fibroblasts in culture and to induce morphological transformation in hamster embryo cells and in mouse C3H cells. 25-Hydroxycholesterol and 20 alpha-hydroxycholesterol are potent suppressors of generation and proliferation of tumor-specific cytotoxic T lymphocytes. Although investigations into the role of cholesterol oxidation products in cancer are still in the early stages, evidence to date indicates a potentially significant role in the induction of some types of cancer.

Familial cancer syndromes: A survey

Several pre-malignant diseases are known to have a genetic etiology. This study focuses attention upon precancerous disorders wherein the mode of inheritance is either well established or wherein it remains unclear even though familial aggregation of the particular diseases have been amply documented. These conditions will be discussed as useful models for systematic investigations of the host etiologic component in carcinogenesis. Our survey of hereditary precancerous syndromes includes multiple polyposis of the coli, the multiple mucosal neuroma syndrome, the Cancer Family Syndrome, Sipple's syndrome, Von Recklinghausen's neurofibromatosus, the multiple nevoid basal cell carcinoma syndrome, tuberous sclerosis, familial cutaneous malignant melanoma, and carcinoma of the breast. We have emphasized the heterogeneous character of many forms of familial cancer. Familial breast cancer associations clearly show such heterogeneity, as do colon cancer syndromes. Certain of these precancerous states are characterized by phenotypes which are clinically apparent, polyposis coli being the classic example. Others, such as Sipple's syndrome are amenable to routine screening for biochemical markers. The bulk of putative genetic cancer-predisposing problems require further basic investigation of modes of inheritance. Cancer control may be enhanced through communication of useful genetic and diagnostic information to primary care physicians. Referral of cancer clusters of possible genetic etiology from clinicians to human geneticists facilitates the necessary basic research.