key: cord-0776199-pwspidcp
authors: Elizabeth McCarthy, Caroline; Fedele, Stefano; Ho, Michael; Shaw, Richard
title: UK Consensus Recommendations on the Management of Oral Epithelial Dysplasia during COVID-19 pandemic outbreaks
date: 2020-11-19
journal: Oral Oncol
DOI: 10.1016/j.oraloncology.2020.105110
sha: 98221e96b1abd8790b11068adf2e022b6c53d256
doc_id: 776199
cord_uid: pwspidcp

Objectives Oral Epithelial Dysplasia (OED) is associated with an increased risk of oral cancer development. The SARS-CoV-2 pandemic is necessitating the suspension or dramatic reduction of face-to-face non-urgent elective services, including OED clinics. Little is known regarding the potential impact of elective services suspension upon the risk of OED progression, and whether alternative strategies (e.g. remote consultations) may be introduced to ensure OED surveillance. The aim of this paper is to provide expert-opinion consensus recommendations for the management of OED during the current and future pandemic outbreaks. Materials and Methods A working group of nine UK-based senior clinicians and academics in Oral and Maxillofacial Surgery and Oral Medicine was created and twelve consensus statements were developed using a modified-Delphi process. Greater than 80% agreement was considered a consensus. Results Consensus was achieved for all twelve statements (89-100% agreement). The group agreed that, during the temporary suspension of elective services associated with COVID-19 pandemic outbreaks, patients with OED can be risk stratified to determine the length of accepted delay in face-to-face consultation. Remote consultations with patient-provided clinical photographs may be a useful way of maintaining a level of surveillance in this group of patients. Conclusions Using an expert working group methodology, we have developed consensus recommendations for the monitoring of individuals with OED during pandemic outbreaks associated with temporary suspension of elective services. This has identified areas of future research and highlighted the need for a stronger evidence base to inform the set-up and delivery of surveillance regimens for patients with OED.

to provide expert-opinion consensus recommendations for the management of OED during the current and future pandemic outbreaks.

A working group of nine UK-based senior clinicians and academics in Oral and Maxillofacial Surgery and Oral Medicine was created and twelve consensus statements were developed using a modified-Delphi process. Greater than 80% agreement was considered a consensus.

Consensus was achieved for all twelve statements (89-100% agreement). The group agreed that, during the temporary suspension of elective services associated with COVID-19 pandemic outbreaks, patients with OED can be risk stratified to determine the length of accepted delay in face-to-face consultation. Remote consultations with patient-provided clinical photographs may be a useful way of maintaining a level of surveillance in this group of patients.

Using an expert working group methodology, we have developed consensus recommendations for the monitoring of individuals with OED during pandemic outbreaks associated with temporary suspension of elective services. This has identified areas of future research and highlighted the need for a stronger evidence base to inform the set-up and delivery of surveillance regimens for patients with OED.

Oral epithelial dysplasia; consensus guidelines; SARS-CoV-2; COVID-19; potentially-malignant oral disorder; oral cancer prevention. There are concerns that this decrease may result in diagnostic delay and a consequent increase in head and neck cancers diagnosed at a more advanced stage in the medium-and long-term 3 , with the need for more complex and costly treatment and poorer outcomes for the affected individuals.

Oral epithelial dysplasia (OED) is a disorder of the oral mucosa associated with an increased risk of oral cancer development: approximately 10% of all OED patients experience disease progression and develop oral cancer with an average time-to-event of approximately 4 years from diagnosis 4 . The likelihood of disease progression increases with higher grades of dysplasia 5 and patients with OED on the lateral tongue 6, 7 and non-smokers may be at higher risk 6, 8 . Loss of heterozygosity, the superficial extension of the affected dysplastic mucosa (e.g. a large dysplastic lesion as opposed to a small one) and a previous history of oral cancer are also established risk factors [8] [9] [10] . There remains little robust evidence supporting any intervention in patients with OED that may reduce the risk of disease progression and ultimately the development of oral cancer. Individuals with OED regarded to be at lower risk of progression are often offered a surveillance programme of regular visual inspections with the option of re-biopsy where clinical manifestations suggest potential disease progression 11 .

Surveillance intervals of 3, 6 or 12 months are commonly considered depending on the grade of dysplasia, clinical assessment of the lesion and previous medical history 11 . Although evidence remains weak due to the lack of well-designed clinical trials, some single-centre observational studies report notably positive outcomes when patients with OED are carefully monitored and surgical intervention offered at an appropriate stage in the disease process 12 .

This is however difficult to achieve with the temporary suspension of elective services during pandemic outbreaks. Little is known regarding the potential impact of deferring regular monitoring upon the risk of OED progression, and whether alternative strategies (e.g. remote consultations) may be introduced so to ensure OED surveillance. Prevention and early detection of oral cancer is of paramount importance to avoid adding to the excess cancer mortality that is already expected as a result of the disruption to services caused by the SARS-CoV-2 pandemic 13, 14 . The aim of this paper is to provide expert-opinon consensus recommendations for the management of OED during current and future pandemic outbreaks. 

Responses from all nine members of the group were received and consensus was achieved in the first round. The twelve statements are presented below together with the level of consensus achieved and the rationale supporting the recommendations.

The group agreed that, during the suspension of elective clinical services associated with a pandemic outbreak, replacing a clinical surveillance face-to-face consultation with a remote consultation is acceptable. The group suggested that the remote consultation should be arranged within 1 -2 weeks of the cancelled face-to-face appointment, in order to ensure consistency, where possible, with the monitoring schedule previously set for that individual patient. Self-examination should be encouraged 15 and information provided on the potential signs and symptoms of OED progression and oral cancer development ("red flag signs and symptoms" -see Table 1 ). Very brief advice (VBA)

should also be provided regarding smoking cessation 16 , limiting alcohol consumption, 17 and cessation of smokeless tobacco and betel & areca nut/paan/gutka chewing in line with national recommendations 18 .

There was strong consensus to support The UK National Health Service (NHS) Cancer Waiting Times

Standards that require patients with suspected cancer are seen within 2-weeks of referral 19 .

Therefore the group suggested that a patient with a known diagnosis of OED and reporting signs and symptoms consistent with development of oral cancer (Table 1) The group agreed that, following the report of "red flag symptoms and signs", any patient seen for an urgent face-to-face consultation should be also offered a biopsy at the same appointment, where deemded necessary and appropriate. The aim is to ensure that the relevant diagnosis is made available within 28 days at the very latest. This timeline is in accordance with the NHS long term plan to improve performance in the early diagnosis of cancer 21 , with a new 28-day faster diagnosis target expected to be introduced in 2020 22 . This approach also reduces the number of hospital appointments, thereby limiting exposure to SARS-CoV-2 23 .

Clinical photographs are important in the long-term monitoring of potentially malignant lesions of the oral mucosa 11 . The group agreed that photographs provided by patients, typically taken with a smartphone, can be a helpful adjunct to the remote consultation and can be stored in the patient records for future reference. The group discussed that not all patients may be be able to take or send photographs for clinical review, or that the quality of the photographs may be poor and not informative (see below). Patients must be made aware that data security cannot be guaranteed when images are sent from their personal email account, as images are not subject to information governance and NHS data protection regulation until they have been received by the healthcare professional 24 .

Verbal or written guidance should be provided to patients for the purpose of achieving goodquality images suitable for surveillance (Consensus achieved: 89%)

There was consensus that verbal or electronic guidance should be provided for patients who are able and willing to take their own clinical images. The group suggested that the the available UK guidance on the use of mobile photographic devices in dermatology 25 

Considering the higher risk of progression to cancer of moderate OED (15% prevalence of oral squamous ceall carcinoma development), 7, 27 the group agreed that an individual risk stratified approach is required for all patients and the use of patient-generated clinical images is instrumental in stratifying patients with moderate OED into two groups. For those individuals with moderate OED that appears clinically stable and unchanged on patient-generated clinical photographs, it would be reasonable to defer their consultation by 6 months. However, should the patient be unable to provide clinical photographs, a face-to-face consultation within 3-4 months is recommended. As per consensus statements 2 and 4, any evidence of disease progression on patient-generated clinical photgraphs should trigger the offer of a a face-to-face urgent appointment within 2 weeks.

There was strong consensus that any delay in face-to-face surveillance examination in cases of severe OED should be minimised, where possible, to within 4-6 weeks of the original, scheduled review. This reflects the annual incidence and prevalence of cancer development in individuals with severe OED being 3.6% 26 and 25% respectively, 7 with some authors suggesting an overall prevalence as high as 50% 27 . Photographs provided by the patient may guide the clinicians' decision and, as per consensus statements 2 and 4, any evidence of disease progression on patient-generated clinical photographs should trigger the offer of a face-to-face urgent appointment within 2 weeks.

The group recognised that, during a pandemic outbreak, individual risk perception may vary and some patients may decline the offer of a face-to-face consultation and ask for a remote consultation instead. Examples include individuals at higher risk of severe COVID-19 clincal syndrome due to medical history, ethnic background or age 28, 29 . Therefore, the group agreed that patients with severe OED declining to attend a face-to-face consultation within 4-6 weeks from their original appointment should be reviewed remotely, with the benefit of clinical images if possible, and offered a new face-to-face consultation within an additional 4-6 weeks. As per consensus statements 2 and 4, any evidence of disease progression on patient-generated clinical photographs should trigger the offer of a face-to-face urgent appointment within 2 weeks.

There was strong consensus from the group that the provision of surgical intervention for high risk OED should be resumed as soon as reasonably possible. The group agreed that, after prioritising time-urgent trauma and cancer cases 23 , where capacity allows, consideration should be given to the resumption of elective surgery for patients with newly diagnosed severe OED, especially during the phase of declining prevelance of the pandemic. The rationale for this recommendation is based on the reasonable intention to reduce the risk of disease progression and future oral cancer development, but also on the observation that in up to 10% of patients with biopsy-confirmed noninvasive lesion the definitive histological diagnosis is upgraded to squamous cell carcinoma following surgical excision 30 .

NHS England recommends that individuals at risk of severe COVID-19 clinical syndrome should be offered remote consultation as first option, and required to attend face-to-face hospital consultations only for urgent reasons 31 . The group agreed that "clinically vulnerable" and "clinically extremely vulnerable" individuals with OED reporting red-flag signs or symptoms or providing clinical photographs suspicious for disease progression should be considered in need of an urgent consultation and offered a face-to-face appointment as per consensus statement 2.

The group recognised that some patients with OED may decline remote consultations and request to attend a face-to-face clinical review. The Royal College of Surgeons (RCS) guidelines state that remote consultations should only be used for patients who are able and willing to communicate via telephone or video 23 . Accordingly, the group agreed that, where capacity allows, the request for a face-to-face consultation may be accomodated. Patients should be counselled on the potential risk of COVID-19 associated with hospital attendance and commuting 23 .

We have developed brief expert-opinon consensus recommendations for the management of patients with OED during pandemic outbreaks associated with temporary suspension of non-urgent elective hospital services. Figure 1 shows a flow chart to summarise these recommendations.

Patients with OED are at increased risk of developing oral cancer compared to the general population 32, 33 and require close clinical monitoring and appropriately-timed surgical interventions 11 .

As there will be a significant backlog of untreated cancer to be managed due to the disruption to cancer services caused by the current pandemic 34 , it would be reasonable to suggest that careful management of OED may prevent disease progession and reduce the burden on already overstretched cancer services.

Evidence on the management of OED, follow-up periods and time intervals between monitoring reviews remains scarce, which prompted the use of a consensus approach in the development of these recommendations. Similar methodology has been successfully used to develop consensus recommendations for head and neck surgical oncology practice during the SARS-CoV-2 pandemic 35 .

These consensus guidelines cannot cover every clinical situation and it is recognised that practice will need to respond to changing infection rates in the community.

Remote consultations have become routine practice within the NHS in the UK in recent months, in order to rationalise the need for travel to hospital and to limit the spread of SARS-CoV-2. Remote telephone triage should be arranged, within 1-2 weeks of the scheduled appointment, to identify patients reporting red flag symtpoms and signs of oral cancer. Such patients should be offered an appointment for physical examination within two weeks, with provision for biopsy on the same day.

The use of photographs provided by patients may aid decision-making about the need for a face-toface consultation. However, the use of patient-provided photographs in the diagnostic and management pathway of OED is novel, requires evaluation, and further work will need to be done to establish the safety and efficacy of this approach. Patient-provided images have been successfully used to triage dental emergencies 36 47 . These recommendations concur with our own that patients with symptoms suspicious for cancer should be evaluated within two weeks. They also suggest a risk stratified approach and suggest patient's with high grade (dysplastic) lesions should be offered proper surgical treatment within three months or a review appointment within six months if a conservative approach is warranted. Patient appointments for review of low-grade lesions can be postponed for 12 months.

The authors accept the evident limitations to the external validity of this Delphi process, as it lacks the context of real-world data. One parallel to illustrate this limitation would be the similarly constructed recommendations in the management of head and neck cancers 35 

COVIDsurg data has demonstrated that some of the conclusions from the earlier consensus process have not been validated by real-world clinical outcome data 48 . The authors of the current manuscript would welcome the clinical validation of this consensus developed for OED.

We should strive to achieve the balance of minimising the risk of additional, preventable oral cancers whilst ensuring the risk of SARS-CoV-2 to staff and patients is sufficiently low to justify a physical examination. It is recognised that remote consultations have limitations when compared to clinical examination of patients with OED, therefore any delay in physical examination due to SARS-CoV-2 must be modest and risk-stratified.

Increasing size of lesion Bleeding on contact with the lesion Increased thickness of lesion New area of persistent redness New onset of paraesthesia New area of persistent ulceration New and persistent neck lump New onset of pain or swelling Table 1 . "Red flag signs and symptoms" of disease progression and/or oral cancer development in patients with OED 20

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The authors would like to thank all members of the working group: Dr Richard Cook, Mr. Jagtar 

None declared Appendix A: Scenarios Discussed by the Expert Panel to inform the development of

Interviews were completed in June 2020

A 60-year-old male patient, smoker with a background of ischaemic heart disease. He has a diagnosis of mild OED on the buccal mucosa from 4 years ago. Has been under 6-month review with OMFS; the most recent clinical photographs from 12 months ago show a homogenous leukoplakia which has reduced in thickness in comparison to initial photographs. He was scheduled for his 6-month review in April 2020 but this was cancelled due to the COVID-19 pandemic and you have been asked to reappoint him. Would you plan to see this patient face-to-face, if so, when? If not, how would you manage his review?

A 50-year-old female with severe dysplasia on the left lateral tongue; non-smoker; 2.5cmx1.5cm lesion; mixed leukoplaka/erythroleukoplakia; diagnosed Feb 2020. She is under the care of oral medicine. She wasn't sure about having surgery at the time so you agreed to arrange a review in 3 months (May 2020). This was cancelled due to the COVID-19 pandemic but you have been asked to review the notes and re-arrange her appointment. Would you plan to see this patient face-to-face? If yes, where and when? If not, how would you manage this situation?

An 80-year-old male smoker, with hypertension, with a diagnosis of moderate OED on the lower left alveolar ridge, around 1.5cm diameter, homogenous leukoplakia. The original diagnosis was made 2 years ago and the lesion has been stable on 6-monthly reviews in the Oral Medicine clinic. What will you do? Will you see this patient face-to-face?

A 58-year old male, non-smoker with a large area of moderate-severe dysplasia on the lateral tongue has been under review for 2 years on the Oral Dysplasia clinic (Oral Medicine dept with OMFS input). Surgery has been discussed but would require free-flap reconstruction and the patient has elected for a 'watchful wait' approach. He was scheduled for his 4-month appointment in May 2020 but this was cancelled due to COVID- 19 and you have been asked to reschedule his appointment. You send a generic letter asking patients to report red flag symptoms and he reports that the lesion has become sore. You ask him to provide clinical photographs of the lesion in question, which appear to show more significant erythroplakia at the anterior edge of the lesion. Will you see this patient face-to-face? How will you manage this situation?

A 75-year-old female who completed treatment for breast ca (surgery, RT and chemotherapy) six months ago.She has a background of lichen planus and a diagnosis of severe OED in the lower left buccal sulcus from 3 years ago (excisional biopsy). She is under the care of OMFS. Mild dysplasia was evident at the margins and there is an area of mild erythema <8mm maximum diameter at the site of surgery. There are multiple other lesions of lichen planus around the mouth. She was reviewed in December 2019 and there were no concerning features. Her review was scheduled for May 2020 but has been cancelled due to the COVID-19 pandemic.Would you plan to review this patient face-to-face? If yes, when, and how would you manage this? If not, how would you manage this case? An 80-year-old male smoker, with hypertension, with a diagnosis of moderate OED on the lower left alveolar ridge, around 1.5cm diameter, homogenous leukoplakia. The original diagnosis was made 2 years ago and the lesion has been stable on 6-monthly reviews in the Oral Medicine clinic. What will you do? Will you see this patient face-to-face?

A 58-year old male, non-smoker with a large area of moderate-severe dysplasia on the lateral tongue has been under review for 2 years on the Oral Dysplasia clinic (Oral Medicine dept with OMFS input). Surgery has been discussed but would require free-flap reconstruction and the patient has elected for a 'watchful wait' approach. He was scheduled for his 4-month appointment in May 2020 but this was cancelled due to COVID- 19 and you have been asked to reschedule his appointment. You send a generic letter asking patients to report red flag symptoms and he reports that the lesion has become sore. You ask him to provide clinical photographs of the lesion in question, which appear to show more significant erythroplakia at the anterior edge of the lesion. Will you see this patient face-to-face? How will you manage this situation?  Risk stratification is suggested so that high-risk cases are prioritised for face-to-face review  Remote consultations may be a useful method for ensuring continuity of review for lower risk cases