Virus-Induced Cancers of the Skin and Mucosa: Are We Dealing with “Smoking Guns” or “Smoke and Mirrors” in the Operating Theatre?

Virus-induced cancers of the skin and mucosa are important causes of total cancer in the world. For instance, human papillomavirus (HPV) is thought to account for ~4.8% of total world cancers each year, and these cancers include ano-genital cancers, and head and neck cancers [5]. In 2006, the WHO classified HPV as a Class I carcinogen. This was in recognition of the worldwide importance of HPV in causing several different types of cancers in different anatomical locations and systems. Alpha group HPV (which tend to infect the genital skin and mucosae) are the dominant group of HPV involved in the ano-genital cancers, and head and neck cancer epidemics currently seen worldwide.

Mutations in skin cell DNA due to ionising UV radiation is by far the most important risk factor for development of skin cancers. Other important risk factors for squamous cell carcinoma (SCC) of skin are white skin, increased age, male sex, and decreased immune status [14]. The link between HPV and SCC skin was initially noted in a specific cohort of patients with epidermodysplasia verruciformis (EV). EV is a rare genetic disorder, most commonly autosomal recessive in its Mendelian inheritance, characterised by decreased cell-mediated immunity and infection by beta group HPV which leads to widespread plaques and papillomas/wart-like lesions, and a high risk of SCC of skin. Beta group HPV 5 and 8 are the types most commonly associated with SCC of skin in these patients [8]. The lifetime risk of developing skin SCC in the USA is thought to range from 7% to 11%, and is estimated to be even higher in Australia [3]. Accurate data on the incidence of skin SCC in the UK is not readily available due to inefficiencies in data collection and the cancer registry system, but is thought to also be increasing [10].

Merkel cell carcinoma (MCC) is a rare neuroendocrine tumour of the skin with highly aggressive behaviour and increasing incidence, and its viral causation has recently been elucidated. MCC has high metastatic potential regardless of the size of the primary tumour and a 5 year disease associated mortality of 46% [12]. MCV was first described in causal association with Merkel cell carcinoma in 2008 by the group led by Patrick Moore at the University of Pittsburgh [4]. Since then, others have confirmed their findings, that infection of susceptible cells in the skin (possibly Merkel cells or dermal stem cells) can lead to viral DNA integration with subsequent clonal replication of infected cells, and this leads to tumour formation.

The annual estimated age standardised incidence rate of MCC in the UK is between 0.1 and 0.2 per 100,000 (1999–2008) and is thought to be increasing [9] (http://​www.​ncin.​org.​uk/​publications/​data_​briefings/​rareskincancer).

In the East of England, the age standardised incidence rates for MCC in males and females are 0.19 and 0.24 per 100 000 person-years, respectively. The total age standardised incidence rate was 0.21 per 100 000 person-years and represents a threefold increase in this region from 2004 to 2013 [9]. The main risk factors for MCC development are high UV exposure, white race (the significance of melanin protection appears important), elderly age (median age at diagnosis is 76.2 years for women, and 73.6 years for men), and immunosuppression.

The prevalence of MCV in the community is extremely common, with 80% of healthy North American adult (blood donors) found to be seropositive for past MCV exposure [16]. Also consistent with this, MCV was detected in 80% of skin swabs from healthy volunteers, and this suggests that it may be a common inhabitant of human skin microflora [6]. The pathogenesis of MCC is clearly not a simple one. Infection with MCV is clearly not sufficient to cause MCC, as demonstrated by the markedly differing incidence with prevalence rates in the population. Therefore, additional cellular and molecular events must occur, probably with viral integration into the cellular genome and loss of immunosurveillance before tumour pathogenesis finally occurs. In this regard, MCV encodes a large T tumour antigen (LT) and a small tumour antigen (sT) which play a role in pathogenesis by targeting several tumour suppressor genes [2].

In this article, we have sought to understand if laser or diathermy smoke is able to transmit virus from skin or mucosa to attending medical personnel, and whether virus transmitted in this way is able to infect and cause cancer in the longer term. We directly review the morphological structure of HPV and MCV, and searched for published evidence whether these viruses are able to persist in smoke and remain viable. We then looked for reports of benign and malignant tumours associated with chronic infection with these viruses.

We undertook a literature search through PubMed Central using different combinations of the words “HPV, human papillomavirus, Merkel cell polyomavirus, MCV, lasers, laser smoke, diathermy, diathermy smoke, plume(s)”. We have preferentially included publications since 2000 to ensure more up-to-date data unless the article found was highly relevant for smoke or diathermy. Exclusion criteria included non-English and non-German articles. Further cross-referencing from the reference lists of these papers and the end results of the search for laser and diathermy smoke publications involving HPV and MCV are discussed below. This article does not contain any new studies with human or animal subjects performed by any of the authors.

The available evidence appears to suggest that there is a possibility that transmission of viruses such as HPV or MCV from patient to surgeon or other theatre staff is a real risk, particularly for repeated laser operations on high-risk sites such as the anogenital area; therefore, it remains prudent to recommend that all available options, such as efficient smoke extraction systems, respirator filtration masks, surgical face masks with particulate filtration, etc., to minimise or prevent surgeon exposure to laser or diathermy smoke should be utilised. Evidence of the development of subsequent malignancies in these gynaecological surgeons is now available. The multifactorial oncogenesis process which leads to malignancy must be fulfilled for cancer to develop, and this is a reason for positivity, because it ensures that the actual risk of developing cancer is low.