Cancer and COVID-19: the two killers of the era. Ever since COVID-19 was declared a pandemic by the WHO earlier this year, life was going to be different. Cancer was known as the killer of the generation, wiping away 9.6 million lives globally every year, with 70 per cent of deaths originating from low- to middle-income countries. [1]
COVID-19 and cancer are also intertwined, though not in a disease-specific manner. COVID-19, like any other viral infection, thrives on the weakness of the immune system of the patient. Cancer cells are no different - an array of mechanisms are employed to evade immune detection and promote inhibition of the efficacy of immunogenic pathways. One major aspect is the massive recruitment or infiltration of T-regulatory cells, also affectionately known as Treg cells. Treg cells suppress immunity by the direct killing of T effector cells, secretion of cytokines, inhibition of dendritic cells (CD80 and CD86) through CTLA-4 binding, and IL-2 consumption (bearing in mind that IL-2 is secreted to promote differentiation of naive T cells into T-Helper Cells 1 and 2 [TH1 and TH2]). [2] The interactions of COVID-19 and cancer eventually lead to poor patient outcomes. Partners in crime, as we call them.
However, it appears that the interactions between COVID-19 and cancer do not stop here. Indeed, COVID-19 has become the major health crisis of the century. The misinformation and deception surrounding this crisis have deprived cancer patients of the care they require. This, in part, boils down to one big thing: the government. In this article, I aim to address the alarming issue of government scaremongering and misinformation, before moving on to my reflections towards a very nicely written Comment published on Lancet Gastroenterology and Hepatology (Rees et al, 2020) regarding the use of endoscopy in the COVID-19 era. [3] The Comment particularly addresses the use of endoscopy in the diagnosis and therapeutic strategies of cancer amidst patient fears of coming to the hospital with COVID-19 raging in healthcare battlegrounds. It also addresses the measures in place to protect patients from exposure to the virus.
The government has acted in various ways: promoting household confinement and the massive curtailment of personal liberties, buttressed by advice against going to healthcare facilities. Throughout the pandemic so far, it (I am not referencing this, for I have been in the UK from the start and I'm speaking from personal experience) has used their press briefings to spread so-called 'health' messages promoting fear and suspicion. Horror stories are propagated through different media channels. I don't have to look far. Published on the day of writing on Yahoo! Finance, Matt Hancock, the Health Secretary of the United Kingdom, is ardent and desperate in his attempts at being the grinch of Christmas. Not by spreading lockdown to different parts of the UK, but by spreading half-baked theories about the new strains of COVID-19. He said cases were rising at a 'dangerous rate' and there was another 'highly concerning' mutant strain spreading from South Africa, in which two cases were identified in the UK. [4] With all due respect, not being a COVID-idiot here, I do trust scientists when they say they are still 'investigating about it'. Indeed, in the same news article, deputy chief medical officer Dr Jenny Harries, said, 'We expect viruses to mutate so this should not come as a surprise.' There is no reason why the government should resort to scare tactics like these. The use of highly emotional wording stokes fires of anxiety that are simply not necessary. After all, there is absolutely no scientific evidence that suggests anything other than that the current strain spreads more quickly. No evidence shows that it is more deadly - i.e. carries a higher mortality rate, or even hospitalisation rate. There is no evidence it leads to higher risk of ventilation use, or organ failure. In fact, there are two examples of genetic changes accrued in microbes through time. They are respectively, genetic drift and genetic shift. Genetic drift occurs due to small, incremental changes in the viral (in the case of COVID-19) genetic material. It happens all the time. That's also the reason why we have different vaccines for the seasonal flu, since the vaccine 5 years ago might not work forever. Genetic shift is the more serious situation, where major genetic changes such as recombination and translocation are effectuated. The resulting viral strain is entirely different and can lead to higher transmission rates since it is less likely that the population has ever encountered the strain before. The Home Secretary's comments are also extremely problematic:
'It's a stronger strain of the virus in the sense that it's more transmittable, it's a bouncy virus.' [5]
I might be young, but never in my lifetime have I encountered the use of such naive language by a person of high office in the government when addressing such a serious issue. We are dealing with a major health crisis and the word 'bouncy' is used. The description that it is a 'stronger' strain is also problematic. 'Stronger' and 'transmissible' (I don't think transmittable is the correct spelling [6]) are also not correlated. A 'stronger' virus can be translated automatically to a virus that leads to higher mortality, lower responsiveness to treatment (or higher rate of resistance to treatment), longer hospitalisation and higher strain-related ICU admissions rate. To sprinkle this with more technical glitter, a 'stronger' virus can mean a strain-induced pneumonia leading to greater severity of disease as adjudicated by CURB-65. [7] The use of such emotionally fuelled words by the Home Secretary, a person of high government office, only serves to stoke fear and apprehension. This causes people with chronic diseases to refuse hospital appointments, even when COVID-19 is not as serious as some of the most deadliest diseases in the world - terminal cancer due to delayed diagnosis.
Shifting to the Lancet Comment, due to the COVID-19 health crisis, endoscopic procedures performed peri-COVID are only 12 per cent as compared to pre-COVID figures. Provision of services is severely curtailed due to lockdown restrictions and government measures. YouGov figures back in June 2020 showed that 42 per cent of respondents felt uncomfortable about attending a routine hospital appointment. The Comment explained that prior to COVID-19, anxiety was the major factor whether the patient was going to attend any of the appointments. This stemmed from fears as to whether the endoscopy would return with worrying results, and whether family support was given. These factors are exacerbated by the government's lack of transparency in decision-making and needless propaganda, as well as the issues faced during the COVID-19 pandemic. The government's press briefings every night created a cumulative toll on patients' mental health and aggravated the concerns of heading off to the hospital for routine testing. Patients might be convinced that routine testing is not as important as avoiding COVID-19. Moreover, during the pandemic, as mentioned by the Comment, carer responsibilities (going back to logistic pressures) and adherence to social distancing are also significant factors affecting whether the patient is going to attend a check-up.
The result of this avoidance is the reduction in cancer diagnoses. This is not a good thing since the reduction is not mapped onto overall incidence. A roughly equal number of cancer cases still occur, but subjected to lower detection rates. This leads to two notable consequences: (1) greater mortality due to the lack of detection, or (2) greater mortality and lower treatment responsiveness due to later detection of the cancer. For instance, hepatocellular carcinoma (the most common type of liver cancer) can be treated with surgical resection, radiofrequency ablation or liver transplantation during the early stage. These modalities lead to high recurrence-free survival and overall survival. However, once a certain period of time has passed and the cancer progresses, notably having metastasised to neighbouring structures and de novo structures within the liver arose, systemic therapy, such as sorafenib, is the only way out. [8] The Comment stated that 2700 fewer patients were diagnosed with cancer in the UK each week, with an excess of cancer deaths potentially reaching 7000 in England and more than 30,000 in the USA. It was also projected that such reduced endoscopy service provision could lead to an increase of 15.3-16.6 per cent of colorectal cancer deaths and 5.8-6.0 per cent of oesophageal cancer deaths. [3]
A balancing exercise has to be done. The Comment stated that only 1 case of endoscopy-contracted COVID-19 was recorded up to the time of publication. This is not to show that the risk of catching COVID-19 is totally negligible. An endoscopy entails close clinical contact. As illustrated in the diagram below, the proximity between the patient and healthcare professionals is likely to pose higher risk of COVID-19 transmission. Healthcare settings have striven to control the nosocomial spread of infectious diseases in general. Measures include the use of symptom checklists, temperature-checking, self-isolation and swab-testing. Strict social-distancing rules are also in place.
This diagram is extracted from: https://www.ibdrelief.com/uploads/files/endoscopy_procedure_small_og_image_301.jpg.
With healthcare facilities rolling out such measures to protect patients, we also have to focus on whether patients value COVID-19 over cancer. The future research direction in this area is not to talk with a paternalistic tone, chastising patients for their inability to weigh and prioritise. We have to understand the reasons behind their decisions. COVID-19 is a totally legitimate concern since it is highly contagious and is likely to cause a greater impact on those with diagnosed cancer and other chronic conditions. Being inflicted by these chronic conditions, at the same time, increases the risk of cancer. For instance, having COPD increases the risk of lung cancer by 11 times if the diagnosis of COPD is made within 6 months of the latter (odds ratio 11.47, 95% confidence interval 9.38-14.02). The risk is 2 times higher when the COPD diagnosis is made 10 years beyond the cancer one (odds ratio: 2.18, 95% confidence interval: 1.87-2.54). [9] One possible direction is to understand the impact of the government on individual decisions to go to routine health checks and screening.
This Comment uses endoscopy as a conversation starter, not one to give the last word on the subject. Endoscopy and other imaging techniques in gastroenterology are similar in this respect. Modalities such as barium studies (using barium sulphate to visualise bowel health through fluoroscopic technology) also require close proximity between the assessor (healthcare professional) and the patient. These imaging techniques are invaluable in making diagnoses. The issue can be answered as well by giving an impeccable response to the question: what if methods other than those requiring close proximity are used to make diagnoses and initiate treatment?
It is true that modern medicine has other techniques to do so. It is true that instead of endoscopy, it is possible to use CT Colonography to detect colon cancer. A study published on the American Journal of Roentgenology showed that the sensitivities of CT Colonography and initial colonoscopy in cancer detection were 100 per cent. Their sensitivities for polyp detection were respectively 90 and 78 per cent. CT Colonography is therefore deemed more superior in this aspect than colonoscopy. [10] However, the accuracy of detection is, sadly, not the only factor to be taken into account in clinical practice. Endoscopic techniques are so entrenched in clinical practice that it is not as easy as it may seem to get rid of them. Moreover, greater costs are incurred as we hike up the ladder and use fancy stuff like CT and MRI. There is also smaller capacity of service. CT and MRI machines are limited, or even not available in all hospitals. Endoscopy, on the other hand, can be performed in many settings and is more widely available. The use of CT and MRI may also entail the addition of contrast, something that is not required of endoscopy (barium studies are another story). Contrast media can lead to side effects, sometimes grave in severity, such as anaphylactic shock and acute kidney injury. It can also be argued that endoscopy can be used for therapeutic indications, exemplified by the resection of masses such as polyps and reduction of bleeding (e.g. argon plasma coagulation), a function unable to be performed with solely CT/MRI techniques.
Taking a broader view of affairs, the problem does not, as well, magically disappear, as we go for alternative modalities. Although not requiring as much physical contact as endoscopy, there is still the issue of walking through the doors of the hospital and attending the appointment. Patients are unlikely to ponder about the precise amount of physical contact incurred in one hospital appointment. They are likely to associate the entire concept of hospital with danger. As we can see, the main problem is the phobia attached to hospitals leading to the failure of making timely detection of budding cancers, not the high infectious rate of endoscopies and related techniques.
I love this Comment for having sent out a strong message in the era of COVID-19. It is the fear of contracting an infectious disease blighting the fear of contracting a more dangerous malady - cancer. The combination of the human fear condition as well as apocalyptic comments made by the government and the press, with no regard to complete scientific accuracy, have contributed to patient withdrawal from ordinary healthcare services, including screening and diagnosis. More studies have to be performed regarding the priorities considered by patients when contemplating whether to attend health appointments or not. It is also crucial, as emphasised by the Comment, to provide as much information as possible in the era of misinformation. Healthcare professionals can disseminate more information about the measures in place, as well as the risks attached to not detecting a cancer earlier. At Bart's Cancer Centre, they have a diagnostic hub for cancer patients. Such patients are separated from the COVID-19 and are subjected to multiple protective measures to ensure maximum safety. [11] In the era of confusion, we as healthcare professionals serve to clarify, not confound. This is how modern healthcare provision should move forward in such troubling times.
*The cover image is extracted from: https://multimedia.scmp.com/infographics/news/china/article/3075382/decoding-coronavirus-covid-19/img/cover.jpg. All credits go to the artist.
References and Further Reading:
[1] Cancer. World Health Organisation. https://www.who.int/news-room/fact-sheets/detail/cancer. Published 2018. Accessed December 23, 2020.
[2] Ohue Y, Nishikawa H. Regulatory T (Treg) cells in cancer: Can Treg cells be a new therapeutic target?. Cancer Sci. 2019;110(7):2080-2089. doi:10.1111/cas.14069.
[3] Rees C, Rutter M, Sharp L et al. COVID-19 as a barrier to attending for gastrointestinal endoscopy: weighing up the risks. The Lancet Gastroenterology & Hepatology. 2020;5(11):960-962. doi:10.1016/s2468-1253(20)30268-5.
[4] Williams-Grut O. More of UK to enter lockdown as second new COVID-19 strain discovered. Yahoo! Finance. https://uk.finance.yahoo.com/news/coronavirus-covid-19-uk-press-conference-23-december-matt-hancock-152008717.html. Published 2020. Accessed December 23, 2020.
[5] Craig J. COVID-19: England set for New Year lockdown as coronavirus variant spreads across UK. Sky News. https://news.sky.com/story/covid-19-england-set-for-new-year-lockdown-as-coronavirus-variant-spreads-across-uk-12169829. Published 2020. Accessed December 23, 2020.
[6] 'Transmissible' or 'Transmittable'?. Merriam Webster. https://www.merriam-webster.com/words-at-play/transmissible-vs-transmittable#:~:text=Transmissible%20and%20transmittable%20are%20both,sound%2C%20light%2C%20or%20data. Published 2020. Accessed December 23, 2020.
[7] Lim WS, van der Eerden MM, Laing R, et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax 2003;58:377-382.
[8] Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391(10127):1301-1314. doi:10.1016/S0140-6736(18)30010-2.
[9] Powell HA, Iyen-Omofoman B, Baldwin DR, Hubbard RB, Tata LJ. Chronic obstructive pulmonary disease and risk of lung cancer: the importance of smoking and timing of diagnosis. J Thorac Oncol. 2013;8(1):6-11. doi:10.1097/JTO.0b013e318274a7dc.
[10] Chung D, Huh K, Choi W, Kim J. CT Colonography Using 16-MDCT in the Evaluation of Colorectal Cancer. American Journal of Roentgenology. 2005;184(1):98-103. doi:10.2214/ajr.184.1.01840098.
[11] Cancer - Barts Health NHS Trust. Bartshealth.nhs.uk. https://www.bartshealth.nhs.uk/cancer. Published 2020. Accessed December 24, 2020.