Dysplasia Clinic Research Articles

​​The Butt of the Joke​: Humour and Queer Care at an Anal Dysplasia Clinic

Based on 12 months of ethnographic fieldwork I conducted at an anal cancer prevention clinic in Chicago, USA, this article considers queer camp humour as a care practice to better understand how providers and patients navigate clinical interactions centred around a stigmatised disease in a taboo body part. Humorous moments infused daily life at the clinic, and I came to see them as a critical feature of the clinic’s uniquely queer environment and a central aspect of the staff’s queer care practices. I argue the campy queer style of humour in the clinic was a vital tool for providing culturally appropriate care, and describe how humour mediated patient-provider interactions, had palliative effects, and managed dirt and bodily excess. The article concludes with a brief discussion of the importance of anthropological attention to humour and joking as forms of care.

Scattering-Based Light-Sheet Microscopy Imaging of Human Papillomavirus–Associated Squamous Lesions of the Anal Canal: A Proof-of-Principle Study

Demand for anal cancer screening is expected to rise following the recent publication of the Anal Cancer–HSIL Outcomes Research trial, which showed that treatment of high-grade squamous intraepithelial lesions significantly reduces the rate of progression to anal cancer. While screening for human papillomavirus–associated squamous lesions in the cervix is well established and effective, this is less true for other sites in the lower anogenital tract. Current anal cancer screening and prevention rely on high-resolution anoscopy with biopsies. This procedure has a steep learning curve for providers and may cause patient discomfort. Scattering-based light-sheet microscopy (sLSM) is a novel imaging modality with the potential to mitigate these challenges through real-time, microscopic visualization of disease-susceptible tissue. Here, we report a proof-of-principle study that establishes feasibility of dysplasia detection using an sLSM device. We imaged 110 anal biopsy specimens collected prospectively at our institution’s dysplasia clinic (including 30 nondysplastic, 40 low-grade squamous intraepithelial lesion, and 40 high-grade squamous intraepithelial lesion specimens) and found that these optical images are highly interpretable and accurately recapitulate histopathologic features traditionally used for the diagnosis of human papillomavirus–associated squamous dysplasia. A reader study to assess diagnostic accuracy suggests that sLSM images are noninferior to hematoxylin and eosin images for the detection of anal dysplasia (sLSM accuracy = 0.87; hematoxylin and eosin accuracy = 0.80; P = .066). Given these results, we believe that sLSM technology holds great potential to enhance the efficacy of anal cancer screening by allowing accurate sampling of diagnostic tissue at the time of anoscopy. While the current imaging study was performed on ex vivo biopsy specimens, we are currently developing a handheld device for in vivo imaging that will provide immediate microscopic guidance to high-resolution anoscopy providers.

Colposcopic and Histopathologic Comparative Interpretations Among Patients Undergoing Evaluation for Cervical Dysplasia in Western Kenya

Objective: To determine the correlation between colposcopic and final histopathologic results amongst patients undergoing a colposcopic evaluation in cervical dysplasia clinics in Western Kenya. Methods: This was a cross-sectional study, conducted among 164 females undergoing colposcopic evaluation across several cervical dysplasia clinics in Western Kenya. Colposcopy and histopathology were performed. Colposcopy findings were graded using modified Reid’s Colposcopic Index (RCI). Bayes’ theorem model was used to determine the sensitivity, specificity, positive predictive value, and negative predictive value. An overall ĸ value was calculated as an estimate of the strength of correlation between colposcopy and histopathology. Results: Mean age of the study participants was 40.6 years. Modified RCI classified 20.7%, 40.2%, and 39.1% between a score of 0–2, 3–5, and 6–8, respectively. Colposcopy classified 0.6%, 38.4%, and 60.1% as normal, cervical intraepithelial neoplasia (CIN) 1 (low risk), and CIN 2–3 (medium–high risk), respectively. Histopathology classified 16.5%, 26.2%, 53.3%, and 3.0% as having normal, CIN 1, CIN 2–3, or carcinoma in situ, respectively. Sensitivity, specificity, positive predictive value, and negative predictive value were 85.3%, 69.7%, 80.3%, and 69.7%, respectively. The estimated strength of correlation between colposcopy and biopsy was relatively strong (ĸ=0.55). Conclusion: There is an association between the discriminatory powers of colposcopy and histology, but colposcopy had a lower specificity when compared to histopathology.

Patient Preferences With Regard to Care Structures for Cervical or Vulvar Dysplasia in Certified Dysplasia Clinics in Germany.

The aim of this study was to evaluate patient preferences regarding cervical dysplasia clinics. Specifically, preferences in terms of diagnostic and therapeutic pathways as well as logistical and structural aspects were addressed to recognize unmet needs and improve existing structures of cervical dysplasia care. This questionnaire-based study was conducted between June and December 2022 at an academic medical center in Southwestern Germany. A total of 226 patients who had an appointment at the certified dysplasia clinic were included. The vast majority of patients (74.8%) preferred counseling at the certified dysplasia clinic in the case of an abnormal finding of the cervix or labia. A prompt appointment (within a maximum of 4 weeks), a timely notification about test results (within a maximum of 2 weeks), a travel time <60 minutes and seeing the same doctor during follow-up appointments were recognized as important aspects. While about half of the patients (53.5%) were indifferent to the sex of the gynecologist, almost all of the remaining patients stated they would prefer to be seen by a female doctor (44.3% female doctor vs. 2.2% male doctor). Most women expect very timely appointments and result notifications. Moreover, they favor short travel times and continuity of care. The identified patient preferences should be considered to increase patient satisfaction and quality of care when developing and optimizing management at specialized dysplasia clinics.

Increasing HPV vaccine interest via standardized multimodal education in an underserved patient population (363)

Increasing HPV vaccine interest via standardized multimodal education in an underserved patient population (363)

Medical complications in children with achondroplasia.

AimTo determine the rates of medical investigations, complications, interventions, and outcomes in children with achondroplasia.MethodChildren and adolescents with achondroplasia born between 2000 and 2019, aged between 0 and 18 years of age, and seen at The Children’s Hospital at Westmead skeletal dysplasia clinic were included. Data were collected retrospectively from clinical records. Standard descriptive statistics were used for analysis.ResultsThe study included 108 participants, 58 males and 50 females. Ninety‐nine participants (91.7%) entered the study at birth. The other nine (8.3%) participants entered the study after birth (mean age = 2 years 4 months, SD = 1 year 8 months). The median age of exit from the study was 8 years 8 months (IQR = 8 years 9 months) with a median follow‐up of 8 years 8 months (IQR = 8 years 9 months). Fifty‐two (48%) participants presented with craniocervical stenosis, 15 (13.9%) with hydrocephalus, 66 (61.1%) with hearing impairment, 44 (40.7%) with sleep‐disordered breathing, 46 (42.6%) with lower‐limb malalignment, 24 (22.2%) with thoracolumbar kyphosis, 10 (9.3%) with symptomatic spinal stenosis, 12 (11.1%) with obesity, and 16 (14.8%) who had at least one admission for respiratory illness. Two children died during the study period.InterpretationWe report contemporary rates of medical complications in an Australian population of children with achondroplasia. Recommendations for surveillance in clinical practice are discussed. This information will help guide clinicians with their expectant management of achondroplasia and provide prognostic information to the families of children with achondroplasia.

Factors That Impact the Timing and Removal of Gastrostomy Placement/Nissen Fundoplication in Children with Bronchopulmonary Dysplasia.

The study aimed to identify factors that impact timing of gastrostomy placement/removal and Nissen fundoplication (NF) in infants with bronchopulmonary dysplasia (BPD). Clinical data were reviewed retrospectively from patients recruited from the Johns Hopkins Bronchopulmonary Dysplasia Clinic (January 1, 2014-December 31, 2018). Patients with gastrostomy tubes (GTs) placed in the neonatal intensive care unit (NICU) were older at discharge (p < 0.001) and less likely to have abnormal upper gastrointestinal series findings (p = 0.005) than those with GTs placed after NICU discharge. Patients with NF had lower mean gestational ages (p = 0.011), longer NICU stays (p = 0.019), more frequent home ventilation requirements (p = 0.005), and greater likelihood of pulmonary hypertension (p = 0.032) compared with those without. Median age of GT removal was 61.6 months. Patients with GTs were weaned from supplemental oxygen and/or home ventilation before GT removal (p < 0.001). Patients with GT/NF were more medically complex than those with GT alone. Patients were more likely to be weaned from home respiratory support before GT removal. · Patients with GT/NF were more medically complex than those with GT alone.. · Patients were more likely to be weaned from home respiratory support before GT removal.. · Patients with GTs placed in NICU were older at discharge and less likely to have abnormal upper gastrointestinal series result..

Characteristics of infants or children presenting to outpatient bronchopulmonary dysplasia clinics in the United States.

Bronchopulmonary dysplasia (BPD) is a common respiratory sequelae of preterm birth, for which longitudinal outpatient data are limited. Our objective was to describe a geographically diverse outpatient cohort of former preterm infants followed in BPD-disease specific clinics. Seven BPD specialty clinics contributed data using standardized instruments to this retrospective cohort study. Inclusion criteria included preterm birth (<37 weeks) and respiratory symptoms or needs requiring outpatient follow-up. A total of 413 preterm infants and children were recruited (mean age: 2.4 ± 2.7 years) with a mean gestational age of 27.0 ± 2.8 weeks and a mean birthweight of 951 ± 429 grams of whom 63.7% had severe BPD. Total, 51.1% of subjects were nonwhite. Severe BPD was not associated with greater utilization of acute care/therapies compared to non-severe counterparts. Of children with severe BPD, differences in percentage of those on any home respiratory support (p = .001), home positive pressure ventilation (p = .003), diuretics (p < .001), inhaled corticosteroids (p < .001), and pulmonary vasodilators (p < .001) were found between centers, however no differences in acute care use were observed. This examination of a multicenter collaborative registry of children born prematurely with respiratory disease demonstrates a diversity of management strategies among geographically distinct tertiary care BPD centers in the United States. This study reveals that the majority of children followed in these clinics were nonwhite and that neither variation in management nor severity of BPD at 36 weeks influenced outpatient acute care utilization. These findings suggest that post-neonatal intensive care unit factors and follow-up may modify respiratory outcomes in BPD, possibly independently of severity.

Impact of heritable disorders of connective tissue on daily life of children: Parent perspectives.

The aim of this study was to investigate parent perspectives on how heritable disorders of connective tissue (HDCT) affect a child's everyday life. In addition, this study aimed to determine if parents seeking health professional services perceive their children with HDCT to have difficulties with activities reliant on hand function. This cross-sectional study used a questionnaire for parents to explore the impact of an HDCT on a child's ability to carry out everyday activities. Parents of children (8-18 years) attending a tertiary connective tissue dysplasia clinic, over a 12-month period, were invited to participate. We analysed 100 surveys completed by parents. Children with Ehlers-Danlos syndrome-hypermobile type, joint hypermobility syndrome (48%) and osteogenesis imperfecta (42%) were the largest diagnostic groups represented. Pain (73%) and fatigue (68%) were the most common symptoms parents perceived to affect day-to-day activities. More parents were satisfied with their child's self-care (61%) than school participation (33%). Keeping up with handwriting (71%) and gross motor activities (70%) were the most frequently reported difficulties at school. Most parents (65%) reported leisure activity difficulties, with pain (64%) and fatigue (60%) as the main contributing factors. This study has provided new knowledge about the concerns of parents with their child's engagement in everyday life including the impact of HDCT on hand function. Further research is needed on effective management strategies to reduce symptoms and improve hand function for these children.

The Cervical Dysplasia Worksheet: A Longitudinal Map of Cervical Dysplasia Cytology and Histology Tests and Procedures

Our objectives were to describe the Cervical Dysplasia Worksheet (CDW), provide evidence of its feasibility to view patient cervical dysplasia results over time, and evaluate patient attitudes toward the tool in the setting of abnormal result follow-up. The CDW augments the ASCCP guidelines for managing abnormal cervical cancer screenings by visually depicting cervical cytological and histological history along a color gradient showing severity. We evaluated tool feasibility by graphing a retrospectively reviewed convenience sample of patient data. A cross-sectional evaluation of the tool was then performed to assess patient attitudes in the setting of either dysplasia or colposcopy clinic. Patients had their data graphed on the CDW and explained to them before their clinical encounter. They then gave general comments about the tool and filled out a short evaluation survey. The large majority of retrospective patient data (N = 167) fit well within the CDW with roughly 20% requiring space for additional comments. Among the 30 patients who participated in our evaluation, almost all agreed (n = 29, 96.7%) that the tool helped them understand their history and results and that they would use the tool in the future. The CDW is a novel tool to display a patient's cervical dysplasia history to visualize treatment and future care while enhancing patient-provider communication. Patient evaluation of the tool was largely positive, and suggestions will be taken into consideration for future modification. Further evaluation of the CDW among healthcare providers is needed to analyze its efficacy in the clinical setting.

A pilot study for early detection of oral premalignant diseases using oral cytology and Raman micro-spectroscopy: Assessment of confounding factors.

This study demonstrates the efficacy of Raman micro-spectroscopy of oral cytological samples for differentiating dysplastic, potentially malignant lesions from those of normal, healthy donors. Cells were collected using brush biopsy from healthy donors (n = 20) and patients attending a Dysplasia Clinic (n = 20). Donors were sampled at four different sites (buccal mucosa, tongue, alveolus, gingiva), to ensure matched normal sites for all lesions, while patient samples were taken from clinically evident, histologically verified dysplastic lesions. Spectra were acquired from the nucleus and cytoplasm of individual cells of all samples and subjected to partial least squares-discriminant analysis. Discriminative sensitivities of 94% and 86% and specificity of 85% were achieved for the cytoplasm and nucleus, respectively, largely based on lipidic contributions of dysplastic cells. Alveolar/gingival samples were differentiated from tongue/buccal samples, indicating that anatomical site is potentially a confounding factor, while age, gender, smoking and alcohol consumption were confirmed not to be.

Raman microspectroscopic study for the detection of oral field cancerisation using brush biopsy samples.

Field cancerisation (FC) is potentially an underlying cause of poor treatment outcomes of oral squamous cell carcinoma (OSCC). To explore the phenomenon using Raman microspectroscopy, brush biopsies from the buccal mucosa, tongue, gingiva and alveolus of healthy donors (n = 40) and from potentially malignant lesions (PML) of Dysplasia Clinic patients (n = 40) were examined. Contralateral normal samples (n = 38) were also collected from the patients. Raman spectra were acquired from the nucleus and cytoplasm of each cell, and subjected to partial least squares-discriminant analysis (PLS-DA). High discriminatory accuracy for donor and PML samples was achieved for both cytopalmic and nuclear data sets. Notably, contralateral normal (patient) samples were also accurately discriminated from donor samples and contralateral normal samples from patients with multiple lesions showed a similar spectral profile to PML samples, strongly indicating a FC effect. These findings support the potential of Raman microspectroscopy as a screening tool for PML using oral exfoliated cells.

Blood pressure in adults with short stature skeletal dysplasias.

Hypertension, compounded by obesity, contributes to cardiovascular disease and mortality. Data describing hypertension prevalence in adults with short stature skeletal dysplasias are lacking, perhaps due to poor fit of typical adult blood pressure cuffs on rhizomelic or contracted upper extremities. Through health screening research, blood pressure was measured in short stature adults attending support group meetings and skeletal dysplasia clinics. Blood pressure was measured with a commercially available, narrower adult cuff on the upper and/or lower segment of the arm. Height, weight, age, gender, diagnosis, exercise, and medications were collected. Subjects were classified as normotensive, prehypertensive, or hypertensive for group analysis; no individual clinical diagnoses were made. In 403 short stature adults, 42% were hypertensive (systolic >140, diastolic >90 OR taking antihypertensive medications). For every BMI unit and 1 kg weight increase in males, there was a 9% and an 8% increase, respectively, in the odds of hypertension versus normotension. In females, the increase was 10% and 6%, respectively. In those with achondroplasia, the most common short stature dysplasia, males (n = 106) had 10% greater odds of hypertension versus normotension for every BMI unit and kilogram increase. In females with achondroplasia (n = 128), the odds of hypertension versus normotension was 8% greater for each BMI unit and 7% for each additional kilogram. These data suggest a high population prevalence of hypertension among short stature adults. Blood pressure must be monitored as part of routine medical care, and measuring at the forearm may be the only viable clinical option in rhizomelic short stature adults with elbow contractures.

Weight gain velocity in infants with achondroplasia.

There are virtually no data regarding appropriate oral intake in infants with dwarfing disorders such as achondroplasia, nor is there clear information regarding appropriate weight gain velocity in this population. Yet, these individuals are at increased risk for both early failure to thrive and, later in life, for obesity. Having appropriate expectations regarding weight gain and reasonable goals in management is imperative. We sought to clarify the rate of weight gain in infants with achondroplasia during the first year of life through analysis of data from 60 infants with achondroplasia seen at least twice during the first year of life in the Midwest Regional Bone Dysplasia Clinic, University of Wisconsin-Madison between 1998 and 2018. The mean weight gain velocity during the first 3 months was 23 g/day which contrasts with 30 g/day in average statured infants. Mean weight gain from 0 to 12 months of age was 13 g/day. The 3% of weight gain velocity during the first year of life was 8 g/day, and this rate did not differ between 0-3 months and 0-12 months of age. Infants with achondroplasia slightly more than doubled their birth weights by 1 year of age in contrast to averaged statured infants who typically triple birth weights by 1 year. Infants with achondroplasia can be thriving but erroneously assessed as failing to thrive if the incorrect reference values are used. This article describes infant weight gain velocity reference data for this population.

Diagnosing uncertainty: The challenges of implementing medical screening programs for minority sub-populations in Canada

The social science literature on medical screening has documented a notable disjuncture between the promises of population-based screening programs and the complex realities of their rollout in everyday practice. We contribute to this scholarship by examining how healthcare providers confront numerous uncertainties associated with the implementation of anal cancer screening programs in Canada given the absence of standardized national evidence-based guidelines. The data was derived from in-depth interviews conducted with 13 physicians and 2 clinical researchers about anal cancer screening for gay, bisexual and other men who have sex with men living with HIV, the minority sub-population at the highest risk for HPV-associated anal cancer. Despite having unknown utility and low specificity, an initial anal Pap test was used to triage patients into anal dysplasia clinics for high-resolution anoscopy. This process led to technological scepticism toward the Pap's accuracy, diagnostic ambiguity related to the interpretation of the cytology results and increased patient anxiety regarding abnormal results. Physicians navigated a tension between wanting to avoid exposing their patients to additional uncertainties caused by screening and pre-cancer treatment and wanting to ensure that their patients did not develop anal cancer under their care. A high number of abnormal anal Pap results paradoxically reintroduced some of the capacity issues that the Pap was meant to resolve, as the existing dysplasia clinics were incapable of seeing all patients with abnormal results. We define this sequence as the epistemic-capacity paradox, a dynamic whereby seeking evidence to improve healthcare capacity simultaneously produces evidence that introduces capacity challenges and generates additional uncertainty. The epistemic-capacity paradox demonstrates the limitations of evidence-based medicine frameworks at determining best practices in the context of rarer health conditions affecting minority sub-populations, where smaller population numbers and limited institutional support pose systemic challenges to the acquisition of sufficient evidence.

Abstract 4219: Mitochondrial DNA damage: A promising tool to screen cervical cancer risk

Abstract Background: Cervical cancer is the 4th most common female cancer, accounting for 500,000 new cases and 200,000 deaths across the world. 99% of cervical cancer is due to infection by human papillomavirus (HPV). The factors leading to HPV integration and induced carcinogenesis are not entirely clear, but high DNA damage levels have been proposed to play a role in HPV integration. Chronic HPV infection increases DNA damage and reduces DNA repair, leading to even higher DNA damage levels. Recently, we showed that the levels of nuclear DNA (nDNA) damage are a potential biomarker predictive of cancer risk. Mitochondrial DNA (mtDNA) damage has been reported to be more persistent than nDNA damage. We have previously demonstrated a good correlation between mtDNA and nDNA damage. Herein, we performed a pilot study to assess whether the levels of mtDNA damage can be used as a potential tool to screen cancer risk. Aims: (1) To measure determine whether the amount of mtDNA damage differs between cervical samples with distinct pathologies. (2) To determine whether the number of mtDNA lesions correlates with the grade of cervical dysplasia. Methods: Ethics Committee approval and written informed consent was obtained from all participants. Samples from 25 patients were collected from the endocervix during a pelvic exam in the Dysplasia Clinic. Samples for DNA damage studies were collected by cytobrush and DNA extracted as previously reported. Demographic and risk factor data were collected through detailed questionnaires. Clinicopathologic data was abstracted from the medical chart. The amount of mtDNA damage was quantified by a long-run real-time PCR-based DNA-damage quantification (LORDQ) assay. Data were analyzed by Student's t-tests. Logistic regression analysis was done modeling the probability of having present pathology risk. Results: Histopathological reports indicated that 9 cervical samples were normal (C0) and 16 had cervical dysplasia. Dysplasia samples were as follows: 9 low-grade squamous intraepithelial lesions (LSILs or C1) and 7 high-grade squamous intraepithelial lesions (HSILs or C2/3). The amount of mtDNA lesions per 10,000 bases were increased two-fold in LSILs or C1 cases and three-fold in HSILs or C2/3 cases when compared to C0. Regression analysis showed no significant correlation between age, race, smoking and drinking status compare with pathology risk. Conclusion: Our data show that mtDNA damage is the lowest in patients without cervical dysplasia and increases progressively with higher grades of dysplasia and correspondent cancer risk. This pilot study shows the feasibility of the approach and stresses the potential of using mtDNA damage to predict cervical cancer risk. Measuring mtDNA damage detection by LORDQ is less time consuming and more cost-effective than the measurement of nDNA damage. Larger population studies are urgently needed to fully assess the potential of this approach for cervical cancer risk. Citation Format: Balaji Sadhasivam, Camille C. Gunderson, Elizabeth H. Hahn, Sarah E. Johnston, Yan D. Zhao, Vengatesh Ganapathy, Lurdes Queimado. Mitochondrial DNA damage: A promising tool to screen cervical cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4219.

Abstract 4223: Conducting community oral cancer screening among South Asians in British Columbia

Abstract Introduction: Globally, more than 300,000 cases of oral cancer are diagnosed annually. South Asian countries, such as India, bear the brunt of this disease due to rampant use of chewing tobacco, betel quid and areca nut. BC has a high proportion of South Asian immigrants. Oral cancer has a high mortality rate (~50% 5-year survival) due to the advanced stage at which it is often diagnosed. It is purported that the majority of oral cancers develop from oral potentially malignant lesions (OPML). While lesions can be easily detected by oral health care providers, it can be challenging to differentiate benign lesions from OPML. DNA aneuploidy has been shown to be an effective marker to predict malignant transformation in OPML. Quantitative cytology (QC) studies DNA content (ploidy) and nuclear morphometric changes within the cell. The aim of this project is to assess the need for oral cancer screening in South Asians in BC and to validate QC as an adjunct screening device in a predominantly South Asian community screening setting to assess its effectiveness in identifying high-risk lesions among visually suspicious lesions. Methods: Demographic information (gender, age, country of birth, ethnicity, risk habit information and dental usage) were collected at the time of screening. Extraoral, intraoral and fluorescence visualization (FV) examinations were conducted. Buccal mucosal brushings were collected from each participant. Brushings were also collected from lesions or areas that had a loss of fluorescence. Thin-layer cytology slides were prepared and stained using Feulgen Eosin. Slides were scanned using the Cancer Imaging Scanner at BC Cancer using machine learning classification algorithms to identify single, in-focus epithelial nucleus. Cells are classified based on DNA ploidy and malignant associated changes. Results: 307 participants were screened of which 303 were eligible. More than 99% of the participants were South Asian or Asian. 104 (34%) lesions were documented: 45 (15%) were high risk (white or red lesions, lichen planus (LP)) and 59 (19%) were low risk (trauma, candidiasis, aphthous ulcers). Twenty participants (7%) were suspected to have high-risk OPMLs (not LP): 12 were referred directly to our Next Gen Oral Dysplasia clinic for biopsy, while 8 were reassessed at 3 weeks. Chewing tobacco was found to be strongly associated with lesion presence (p&amp;lt;0.01). QC analysis is ongoing for 320 samples. To date, 5 biopsies have been performed resulting in 1 mild dysplasia, 1 severe dysplasia and 3 hyperplasia. Conclusion: South Asians in BC were found to be at high risk for OPMLs. QC may help to improve the sensitivity and specificity of oral cancer screening by distinguishing false FV positive inflammatory lesions from high-risk lesions. Citation Format: Leigha D. Rock, Madhurima Datta, Denise M. Laronde, Anita Carraro, Jagoda Korbelik, Alan Harrison, Martial Guillaud. Conducting community oral cancer screening among South Asians in British Columbia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4223.

MINIMALLY-INVASIVE ORAL EXFOLIATED CELLS STUDY FOR PREMALIGNANT LESIONS USING RAMAN MICROSPECTROSCOPY

Squamous cell carcinoma of the oral cavity ranks as the 15th most common cancer in the world and the 10th most frequent cancer in males. The present study was undertaken for the development of new methods for early oral cancer detection based on Raman microspectroscopy of exfoliated cells. Exfoliated oral cells were collected by brush biopsy from patients attending Dublin Dental Hospital Dysplasia Clinic (25) and from healthy volunteers (25). Samples of exfoliated cells from normal mucosa and from pre-malignant lesions were collected using an endocervical cytobrush and placed in ThinPrep vials. Slides were prepared using the Thinprep2000 processor with the aim of forming a monolayer of cells for analysis. Raman spectra were acquired from the nucleus and cytoplasm of each cell using an XploRA confocal Raman instrument (HORIBA JobinYvon). As source, a 532 nm laser was focused by a 100X objective onto the sample and the resultant Raman signals were acquired in the 400 to 1800 cm−1 region. Glass spectral contamination was removed using extended multiplicative signal correction Following pre-processing, spectra were subjected to principal component analysis (PCA) and principal component-linear discriminant analysis (PC-LDA). The results show that Raman spectroscopy coupled with PCA could differentiate the nucleus and cytoplasm of the cell, the PC loadings showing that the cytoplasmic regions are dominated by protein bands while thenuclear regions are dominated by DNA bands. Furthermore, patient samples were discriminated from healthy volunteers based on DNA and lipids bands inthe PC loadings. Sensitivities of 91% and 97% and specificites of 98% and 89% were achieved for the cytoplasm and nucleus respectively, using PC-LDA. Thus, the findings of the study support the potential of Raman microspectroscopy for providing molecular level information from oral exfoliated cells and the future potential for screening of minimally invasive brush biopsy samples for oral pre-cancer and cancer.

Does Undetectable = Untransmissable?

Does Undetectable = Untransmissable?

Multicenter study of mortality in achondroplasia.

Sudden death and higher mortality are recognized in achondroplasia, with acute brainstem compression, a common cause of mortality in children <4 years and cardiovascular deaths being more prevalent in adults. Although, changes in clinical management have improved survival, mortality is still higher than in the general population. The aim of this multicenter clinic-based study was to assess the rate and causes of mortality in patients seen in clinic since 1986. Information was ascertained for achondroplasia patients clinically assessed in four skeletal dysplasia clinics. Data was sent to the National Death Index to identify vital status and cause of death. Standardized mortality rates (SMR) were calculated based on U.S. populations from 1975, 1995, and 2000. Eight hundred fifty-five patients were identified, contributing 12,117 person-years and a total of 12 deaths. One case died in infancy. In the 1-4 year age group, which had the highest age-adjusted SMR, three out of five deaths were because of cerebrovascular/cardiovascular events. Half the deaths in ages 5 through 24 were because of accidental events, including motor vehicle accidents. Decreased mortality in children with achondroplasia was noted, particularly in younger age groups. This improvement in childhood survival is outpaced by improved survival in the general population. Causes of death in these patients have shifted over the last 30 years, with fewer sudden death and deaths because of pneumonia or hydrocephalus countered by more cardiovascular or cerebrovascular and accidental deaths. Clinicians should be aware of the apparent increased risk of vehicular accidents and counsel patients accordingly.