Oral cancers (cancer of the mouth and cancer of the throat) are the sixth most common cancer worldwide, accounting for an estimated 4% of all cancers. There is a higher frequency of these cancers in men. Smoking, alcohol consumption and betel quid chewing are the main risk factors. Cancer of the throat is associated with infection from the human papilloma virus (HPV), which can be transmitted through sexual contact. Low socioeconomic status (a measure of a person’s income, education and occupation in relation to other people’s) is associated with a higher frequency of oral cancers and poorer survival rates. Survival following a diagnosis of mouth or throat cancer remains poor, with around 50% of people still alive at five years (five-year survival rate).
New therapies targeted at the cells that give rise to oral cancers are being developed. The advantage these may have over conventional chemotherapy is that rather than affecting both healthy and cancerous cells they just target cancer cells. Immunotherapy (also known as biological therapy, biotherapy or biological response modifier therapy) may improve the functioning of the immune system so it is more effective at destroying cancer cells. Local immunotherapy delivers treatment directly into the tumour and systemic immunotherapy targets the whole body, and may be useful for stopping the cancer spreading or the return of primary tumours in more advanced cancer.
What was the research?
A systematic review of the evidence to find out whether using new kinds of therapies for treating cancer of the mouth (oral cavity cancer) and cancer of the throat (oropharyngeal cancer) are effective when used together with standard treatments. One of these new therapies is the targeting of cancer cells directly, while the other aims to boost the body’s own immune system to combat the cancer more effectively. Do these treatments result in differences in overall survival and cancer-free survival?
Who conducted the research?
The research was conducted by a team led by Kelvin K. W. Chan, on behalf of the Cochrane Oral Health Group. Anne-Marie Glenny, Jo C. Weldon, Susan Furness, Helen V. Worthington and Helen Wakeford were also on the team.
What evidence was included in the review?
Data was extracted from 12 randomised controlled trials. A total of 2,488 people with tumours in the mouth or throat participated in the trials. Three comparisons were considered:
- People were randomly assigned to either standard treatment for oral cancer, or to receive standard treatment plus the targeted therapy epidermal growth factor receptor monoclonal antibody (EGFR mAb)
- People were randomly assigned to either standard treatment for oral cancer or to receive standard treatment plus the targeted therapy tyrosine kinase inhibitors (TKIs)
- People were randomly assigned to either standard treatment for oral cancer or to receive standard treatment plus immunotherapy
What did the evidence say?
We found that adding EGFR mAb, a targeted therapy, to standard therapy may increase overall survival, cancer-free survival, keeping the cancer limited to that area of the body and may decrease recurrence of the cancer. However, it may result in an increase in skin problems for some.
There is not enough evidence to know whether TKIs added to standard therapies results in a change in overall survival, cancer-free survival, keeping the cancer limited to that area of the body or recurrence of the cancer.
One study suggested that a type of immunotherapy, rIL-2, combined with surgery, may increase overall survival.
How good was the evidence?
Overall, the evidence available ranges from moderate quality (for EGFR mAb) to very low quality (for TKIs and rIL-2), which limits our confidence in the reliability of our findings.
What are the implications for dentists and the general public?
There is some evidence from this review that administering monoclonal antibodies (mAb) against the epidermal growth factor receptor (EGFR) in combination with standard therapies can improve the outcomes in people with oral cavity and oropharyngeal cancers. Moderate quality evidence indicates that EGFR mAb concomitant with standard therapies increase overall survival and locoregional control when compared with standard therapy alone. It is promising that there is no evidence that side effects are significantly increased, with the exception of evidence of an increase in skin toxicity and rash in the case of cetuximab.
While there is some suggestion from the progression-free survival and overall survival data that adding mAb to radiotherapy may improve these outcomes whilst mAb to chemoradiotherapy may not, as yet we cannot be confident in this conclusion and much more evidence is required before any changes to clinical practice are made on this basis.
What should researchers look at in the future?
Further research into the efficacy of targeted therapies is needed. Several outcomes for different interventions have only been evaluated through single trials, and independent replication of these studies is needed. None of the included studies was at low risk of bias, so standards of conduct in randomized controlled trials in this area need to be improved.
Chan KKW, Glenny A-M, Weldon JC, Furness S, Worthington HV, Wakeford H. Interventions for the treatment of oral and oropharyngeal cancers: targeted therapy and immunotherapy. Cochrane Database of Systematic Reviews 2015 , Issue 11 . Art. No.: CD010341. DOI: 10.1002/14651858.CD010341.pub2 .