Squamous cell carcinoma and dental implants: A systematic review of case reports.

Cancer is one of the leading causes of death world-wide. Apart from the most common etiopathological factors related to cancer, at times very rare causes such as irritant or foreign body induced carcinogenesis is not to be overlooked. To systematically review case reports concerned with the association between dental implants and oral squamous cell carcinoma. A Medline (PubMed), Cochrane database, and Google Scholar search was conducted of dental article published in English related to case reports concerned with oral squamous cell carcinoma occurring around dental implants from 2000 to 2014. Twenty articles were retrieved, which included 20 rare case reports which were systematically reviewed and the results were obtained pertaining to age, clinical symptoms, habits, previous history of cancer, potentially malignant disorders, systemic illness, and local factors. It is imperative to identify promptly persisting inflammation associated with implants. Since malignancy may disguise as periimplantitis, especially in patients who are at risk with contributing prominent predisposing factors.

The history of prosthodontic care in replacing missing teeth dates back to 100–1500 AD (Mayan Indian period) and that of implants dates back to 1965.[1] Among the various oral rehabilitation measures adapted by prosthodontists, dental implants play a very prominent and promising role.[2] Beyond the potential benefits and success of dental implants distressingly at occasions it is a debated scientific fact that periimplantitis, which is a complication of implant therapy could very rarely result in inflammation-induced carcinogenesis (oral squamous cell carcinoma). However, there is a dearth in the literature regarding this concept. Hence, we have carried out a systematic review of the rarest available case reports related to it, to explore this challenging concept in the existing literature.[34]

Study Design

Data sources

A systematic review of case reports was conducted using Medline (PubMed), Cochrane Database and Google Scholar using the terms: Medical Subject Heading “dental implants” and “squamous cell carcinoma,” “periimplantitis” and “squamous cell carcinoma,” “inflammation and cancer” and using the Boolean operator “AND” in an attempt to explore literature related to the association between dental implants and oral squamous cell carcinoma.

The data search was restricted to English-language case reports.

Data selection

The data were selected by excluding orthopedic and biomaterial articles and including only dental related articles. A total of 20 exclusive dental related articles published between 2000 and 2014 with 20 rarest case reports concerned with dental implants and oral squamous cell carcinoma was retrieved.

Data extraction

The data pertaining to all the articles were extracted according to patient's age, clinical symptoms, smoking and alcohol habits, previous history of oral cancer and cancer of other regions, existing or prior history of potentially malignant disorders, systemic illness and local factors such as trauma.

Results

Data synthesis

The data synthesis revealed that all the patients were in the age group of 60–80 years except one case, wherein the patient was 42 years. With respect to clinical symptoms, it was found that all the patients presented with periimplantitis. Habit history related to smoking and alcohol was positive in all except 2 patients. In 6 patients, there was a previous treatment history of oral cancer who had taken up implants as part of the rehabilitation process and in 2 patients there was preexisting potentially malignant disorder such as oral lichen planus. In 2 patients there was previous treatment history of other parts of body such as colon cancer and cancer of spine, in 1 patient there was metastasis around dental implants, wherein the primary was from the lung, systemic illness was present in 3 cases, which included diabetes; arterial hypertension, hyperuricemia, ventricular arrhythmias and hypothyroidism respectively. Interestingly in one case report there was no habits, systemic illness, previous history of cancer or any existing potentially malignant disorder, but the history of trauma. All the cases were diagnosed with biopsy and treated and followed up.

Discussion

The systematic review of literature on the association between dental implants, periimplantitis and oral squamous cell carcinoma reveals the fact that the concept of inflammation-induced cancer dates back to 1863, when Virchow first noted that cancer occurs at regions of chronic inflammation,[5] which was further supported by several epidemiological studies.[6] This concept was further explored with respect to reactive oxygen and nitrogen species generated by inflammatory cells, which were suspected to play a pivotal role in causing mutation and leading to cancer formation.[7]

A developing malignancy is populated with diverse inflammatory components such as polymorphs, dendritic cells, macrophages, allergy cells, mast cells, and lymphocytes. These cells produce a variety of cytokines and cytotoxic mediators such as reactive oxygen species, matrix metalloproteinases (MMPs), tumor necrosis factor-alpha (TNF-alpha), interleukins (ILs), and interferons.[89]

The key component in the inflammatory microenvironment in carcinogenesisis the macrophage. Tumor-associated macrophages (TAM) interestingly both inhibit anti-tumor mechanism as well as promote tumorigenesis mechanism. Inhibition of anti-cancer mechanism is achieved with the aid of IL-10 and prostoglandin E2,[10] whereas vascular endothelial growth factor (VEGF), endothelin-2 and urokinase-type plasminogen activator (angiogenic factors) facilitate cancer formation.[11] TAM also liberates IL-1, which is connected with upregulation of VEGF transcription.[12] They also generate MMP-2 and -9, which are responsible for the destruction of extracellular matrix and basement membrane.[13] Apart from the key component other significant components of the inflammatory microenvironment include activated mast cells, neutrophils, cytokines such as IL, TNF-alpha, growth factors and differentiation factors, chemokines, nuclear factor kB, inducible nitric oxide synthase and hypoxia-inducible factor 1 alpha.[14151617181920]

Conclusion

It has been inconclusive if dental implants per se are associated with carcinogenesis. However, significant emphasis has been laid on primed mucosa wherein habits and also other potential contributing factors play a pivotal role in the causation of cancer synergistically with the complication of implant therapy such as periimplantitis. Hence instead of just considering implants as an incidental factor it would be more appropriate to be careful regarding malignancies disguised as periimplantitis and to assess patient risk profiles before considering them for implant therapy. Furthermore, it would be a timely decision to consider such group of patients under the low threshold for biopsy when signs of implant complication such as per implantitis are present. Ultimately though implants occupy a highest form of oral rehabilitation measure in the current era, yet careful patient selection criteria and lifelong systematic follow-up is mandatory to prevent surprising complications such as cancer.