> What is INTERPHONE?
> What is the INTERPHONE research aim?
> Does INTERPHONE include children?
> How many people and what age group was studied?
> What cancers did INTERPHONE look at?
> INTERPHONE results
> Will the INTERPHONE study continue?
> INTERPHONE funding
> Will INTERPHONE tell us once and for all if mobile phones cause cancer or not?
> Long term research beyond INTERPHONE
> Summary on health

Additional Resources
> INTERPHONE - What the health experts say
> INTERPHONE - Scientific summary and key points

What is INTERPHONE?

INTERPHONE is a World Health Organization (WHO) research project coordinated by a WHO agency to assess whether mobile telephone use is associated with an increase in cancer risk.

INTERPHONE consists of national case-control studies in 13 countries and is co-ordinated by the International Agency for Research on Cancer (IARC). 

The INTERPHONE International Study Group, made up of 21 scientists was responsible for the progress of the study, the choice of analyses to be conducted, and the interpretation and publication of results. All the decisions about the study were made exclusively and collectively by the INTERPHONE International Study Group.

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What is the INTERPHONE research aim?

The aim was to assess whether radio frequency exposure from mobile telephones for 5 to 10 years is associated with brain and nervous system cancer risk in adults.

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Does INTERPHONE include children?

No - There were not enough children using mobile phones when INTERPHONE was set up (late 1990s). The numbers would have been too small to find associations with disease.

In March 2009, the start of a new research project specifically focused on young people called MOBI-KIDS was announced.  MOBI-KIDS involves research groups in 13 countries and plans to study about 4000 young people between 10 to 24 years over a 5 year period.

Click here for more information on MOBI-KIDS

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How many people and what age group was studied?

The researchers compared past mobile phone usage of over 6000 people who have particular types of head and neck tumours (called cases) with a similar number of healthy people (called controls) to look for a possible association between mobile phone use and tumour development.

The estimation of past mobile phone use mainly relied on people’s ability to remember how often and for how long they have been using a mobile phone.

INTERPHONE focused on relatively young people 30-59 who had the highest mobile phone use 5 to 10 years before the start of the study.

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What cancers did INTERPHONE look at?

INTERPHONE included people with certain tumours of the head and neck.

These tumours are closest to the location of where a mobile phone is typically used and are in the part of the head receiving some of the highest exposures from a mobile phone.

The tumours studied were:

• Brain Tumours – Glioma and Menigioma 
• Neck Tumours – Parotid Gland
• Inner Ear Tumours - Acoustic Neuroma 

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INTERPHONE results

Brain Tumours - Glioma and Menigioma (Published 18 May 2010)

In May 2010, the INTERPHONE researchers published the results of the combined analysis for glioma and meningioma and found overall no increased risk of brain cancer from mobile phone use.

In announcing the results for glioma and meningioma, Dr Christopher Wild, Director of the International Agency for Research on Cancer (IARC) said:

"An increased risk of brain cancer is not established from the data from INTERPHONE. However, observations at the highest level of cumulative call time and the changing patterns of mobile phone use since the period studied by INTERPHONE, particularly in young people, mean that further investigation of mobile phone use and brain cancer risk is merited.'"

The INTERPHONE researchers conclude:

“Overall, no increase in risk of glioma or meningioma was observed with use of mobile phones. There were suggestions of an increased risk of glioma at the highest exposure levels, but biases and error prevent a causal interpretation. The possible effects of long-term heavy use of mobile phones require further investigation.” 

So what are the biases and error, and what does this actually mean?

With respect to the ‘biases’, some of the studies testing the accuracy of participants' recall of past mobile phone use show that cases (people with brain tumours) tend to overestimate mobile phone use more than the controls (people without tumours). This is termed differential recall bias and can effect the overall research conclusions.

With respect to ‘error’, the INTERPHONE researchers concluded that there were implausible call durations reported by some participants in the highest use group (of up to 12 hours per day), and this can effect the overall research conclusions. This is why the researchers conclude that possible effects of long-term heavy use of mobile phones requires further investigation. 

Click here for the INTERPHONE paper (May 2010)

Click here for the IARC press release (May 2010)

Neck Tumour - Parotid Gland (to date)

In October 2008, IARC published an update that included the results to date for parotid gland tumours and said no increased risk was observed overall for any measure of exposure investigated. It is expected the final analysis will be published before May 2011.

Inner Ear Tumour - Acoustic neurinoma (to date)

In October 2008, IARC published an update that included the results to date for acoustic neurinoma. The 2008 INTERPHONE update said most national studies provided little evidence of an increased risk and that the numbers of long-term heavy users in the individual studies were small and prevent any definitive conclusion about possible association between mobile phone use and risk of these tumours. It is expected the final analysis will be published before May 2011.

Click here for the October 2008 INTERPHONE Update from IARC

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Will the INTERPHONE study continue? 

Yes, the INTERPHONE study will continue with publication of additional analyses of mobile phone use and tumours of the acoustic nerve and parotid gland.

In addition, IARC has scheduled a comprehensive review of the potential for mobile phone use to cause cancer for 24-31 May 2011.  At that time IARC will consider all published epidemiological and experimental evidence, including the new data from the INTERPHONE study.

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INTERPHONE funding 

INTERPHONE received funding from the European Commission, the mobile industry and national authorities in several of the participating countries. Industry funds are administered via a firewall and the sponsors do not have access to any results of the studies before their acceptance for publication. Industry funding was about 25% of the total budget.

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Will INTERPHONE tell us once and for all if mobile phones cause cancer or not?

No.  INTERPHONE’s aim was to assess whether radio signals from mobile phones for 5 to 10 years of use is associated with increased brain and nervous system cancer risk in adults.

Previously published INTERPHONE results have not shown evidence of increased risk for brain and nervous system tumours for up to 10 years of mobile phone use.

INTERPHONE now reports results up to 12 years of mobile phone use, and continues to find no evidence of increased risk.  However, results for more than 10 years of use need to be interpreted with caution as these represent only about 10% of the study subjects. There is also some evidence of recall bias by cases and controls, whereby cases are more likely to overestimate their past phone usage.

The position of the WHO and the conclusion of more than 30 independent authoritative reviews of the whole body of science published during the past eight years is that present safety guidelines are protective of all persons.

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Long term research beyond INTERPHONE

Following on from INTERPHONE, a new long term research project called COSMOS (Cohort Study of Mobile Phone Use and Health) has commenced which aims to follow the health of 250,000 European mobile phone users over 25-30 years.

Click here for information on COSMOS

In March 2009, the start of a new research project specifically focused on young people called MOBI-KIDS was announced.  MOBI-KIDS involves research groups in 13 countries and plans to study about 4000 young people between 10 to 24 years over a 5 year period.

Click here for information on MOBI-KIDS
 

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Summary on Health

We can be reassured by the results that the INTERPHONE scientists have found no increased risk of brain cancer from mobile phone use.

INTERPHONE cannot provide us with a clear answer for the risk of cancer for mobile phone use beyond 12 years because of the small numbers of long term users in the study, so further studies looking at long term risk are ongoing

Overall, the World Health Organization monitors scientific research on mobile phone safety and concludes:

"A large number of studies have been performed over the last two decades to assess whether mobile phones pose a potential health risk. To date, no adverse health effects have been established as being caused by mobile phone use."

WHO Fact Sheet 193 June 2011 - Electromagnetic fields and public health: mobile phones http://www.who.int/mediacentre/factsheets/fs193/en/index.html
 

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INTERPHONE - What the health experts say
INTERPHONE - Scientific summary and key points

Additional resources...

 

 

 

 

 

 

 

 

 

 

 

 

 

 

> What is a case-control study?
> Problems with case-control studies
> Analysis of results
> Diseases included in INTERPHONE
> Information on head and neck tumour desease rates
> INTERPHONE funding
> IARC INTERPHONE press release (May 2010)
> IARC INTERPHONE paper (May 2010)
> ICNIRP INTERPHONE statement (May 2010)
> WHO fact sheet 193 - Electromagnetic fields and public health : mobile phones
> ICNIRP Paper July 2011 - Mobile Phones, Brain Tumours, and the Interphone Study: Where are we now?

What is a case-control study?

The purpose of a case-control study is to determine whether past exposure to one or more risk factors in people who have a disease of interest is the same as that in people without the disease. By comparing exposures in people with and without diseases it could be possible to find out whether exposure to the particular risk factors caused the disease.

Case control studies are cheaper, easier and quicker to carry out than cohort studies.

A case control study involves the collections of cases, people who already have the disease of interest. Cases included in a study will typically be those who were diagnosed within a defined time period. In addition, controls are collected who are people who do not have the disease in question but are as similar in possible to the cases in all other ways.

Both cases and controls are then investigated to assess the amount of exposure they have had to the proposed risk factor. If more cases have been exposed to the risk factor, it could be possible that exposure to the risk factor caused the disease.

For the INTERPHONE study, cases of acoustic neuroma, glioma, meningioma and parotid gland tumours [links to disease explanations for all these] were collected by the researchers in each of the 13 participating countries. The researchers identified cases by liaising with relevant clinics and hospitals in order to ask people who were diagnosed within the chosen time period if they would take part in the study. The period for inclusion in the INTERPHONE study was roughly diagnosis between 2000 and 2002, although the exact 2 year period varies from country to country.

The national research teams of INTERPHONE used slightly different ways of selecting controls. A common method they used was random selection of controls from the national population registries.

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Problems with Case Control Studies

Case-control studies are subject to a number of biases, which could lead to false or invalid results. In the better case-control studies, researchers will carefully assess the impact of potential biases on their findings.

Recall Bias

Recall bias is a particular problem in case-control studies. Without reliable records, the exposure assessment is based on the participants’ recollection. Patients who have a disease are more likely to report exposure to an alleged risk factor than people without disease.

This is potential problem with the INTEPRHONE study. People who have the diseases being investigated could be more likely to report that they have used a mobile phone and report higher usage than people without the diseases. Problems with recall bias could result in differential misclassification.

Participation Bias

Case-control studies are also subject to participation bias. There are a number of different forms or participation bias, for example cases (people with disease) could be more likely to take part than controls (people without disease). Also, in the INTERPHONE study perhaps cases who are heavy mobile phone users are more likely to agree to take part than cases who are low users or do not use a mobile phone at all, for example. The same could be true for controls.

Confounders

A confounder is a factor (or factors) which influence the risk of developing a disease and is not the risk factor being studied. For example if a study was examining the association between alcohol and heart disease, cigarette smoking is a confounder because smoking is known to cause heart disease.

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Analysis of Results

Odds Ratio

The odds ratio is a commonly used measure of association in epidemiology.  The odds are the chances in favour of one side in relation to another and the measure is called an odds ratio because it is simply one set of odds divided by another.

The odds, in epidemiological context, are the chances of being exposed (or diseased) as opposed to not being exposed (or diseased).

If a disease is associated with an exposure, then the odds (or chance) of being exposed in the diseased group will be higher than the odds (or chance) of being exposed in the control group.

Odds ratios are calculated by constructing a 2 x 2 table as shown in the example below. 

Risk factor/exposure	Disease Group
	Case	Control
Exposure	25(a)	10(b)
No Exposure	75(c)	90(d)

The odds of exposure in:

Case group a÷c = 25÷75 = 1/3

Control group b÷d = 10÷90 = 1/9

The odds ratio

OR = a÷c = 25÷75 = 1/3 = 3.0
         b÷d = 10÷90 = 1/9

Confidence Intervals

Confidence limits are used to express the degree of certainty in the mean value given (in case control studies usually the odds ratio). Conventionally, 95% confidence intervals are used, although they can be calculated for 99% or any other value.

A 95% confidence interval is the interval in which will include the true population value in 95% of cases.

Eg. The mean diastolic blood pressure is 82.696 mmHg (95% CI = 80.509 – 84.883).

In this example, although the sample mean is 82.696 mmHg, there is a 95% probability that the true population mean lies between 80.509 and 84.883. In this example, the range of the confidence intervals is quite narrow, indicating that the true population mean is not far away from that given, ie there is a high degree of certainty in the figure 82.696 mmHg. Conversely, if the confidence intervals were wide then this could indicate that the true population mean is far away from that estimated.

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Diseases included in INTERPHONE

> Parotid Gland
> Glioma
> Meningioma
> Acoustic Neuroma

Parotid Gland (Salivary Gland) Tumor

What are the salivary glands?

Salivary glands make spit (saliva) and keep your mouth and throat moist. Saliva provides minerals that help keep your teeth healthy. It also helps make swallowing and digestion of food easier.

There are salivary glands, 

• Just under the lobes of your ears (parotid glands)
• Under each side of your jaw (submandibular glands)
• Under your tongue (sublingual glands)

There are also minor salivary glands. These are small collections of salivary gland tissue, scattered throughout the throat and mouth.

What is salivary gland cancer?

Salivary gland cancer comes under a group of cancers called head and neck cancer. It is a rare type of cancer. It is much more common to find a non cancerous lump (benign tumour) in these glands. The parotid gland is the most common place to find a cancerous tumour. But only about 1 out of every 5 tumours (20%) found in the parotid gland are cancerous. A small number are found in the submandibular gland and even less in the other glands. Benign tumours usually grow slowly over months or years and are usually hard and painless. Cancerous tumours tend to grow more quickly and cause pain and tenderness.

Treatment

Treatment for less aggressive tumours that grow slowly is surgery. Removing a parotid gland tumour usually means having an operation called a parotidectomy. Because an important nerve runs through this gland, surgery can be tricky. This is the facial nerve, which controls the movement of muscles in your face, including your eyes and mouth. Damage to this nerve can cause drooping of the eyebrow or corner of the mouth, lips that cannot be held together tightly or an eye that doesn't close properly. Your surgeon will take every care to make sure this doesn't happen, but it may be unavoidable. You may want to ask your surgeon about this if you are concerned.

With faster growing, more aggressive tumours you may need a combination of surgery and radiotherapy. These tumours are more likely to spread to nearby tissue and to the lymph nodes in your neck. If this happens you will need an operation to remove the lymph nodes on the same side of the neck. This is called a neck dissection. 

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Glioma

There are nearly 100 different types of brain tumours. They are generally named after the type of cell from which they developed from. Most brain tumours develop from the cells that support the nerve cells of the brain. These are called glial cells. A tumour of glial cells is called a glioma.

GRADE - BENIGN OR MALIGNANT?

Brain tumours are put into groups according to how fast they are likely to grow. There are 4 groups called grades 1 – 4. The cells are examined under a microscope. The more normal they look, the more slowly the brain tumour is likely to develop and the lower the grade. The more abnormal the cells look, the more quickly the brain tumour is likely to grow and the higher the grade. Low grade gliomas (grade 1 and grade 2) are the slowest growing brain tumours.

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Meningioma

About 1 in 4 brain tumours in adults (25%) is a meningioma. They are more common in older people and in women. These are tumours growing in the tissues covering the brain. They are most often found in the forebrain or hindbrain. They are usually benign (not cancerous).

Some meningiomas are 'atypical'. This means that they behave more aggressively than normally expected for meningiomas. They can grow into surrounding brain tissue and may come back after they have been removed.

Meningioma symptoms vary a lot, depending on where in the brain they are growing.

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ACOUSTIC NEUROMA

What is Acoustic Neuroma?

An acoustic neuroma (also called neurinoma or vestibular schwannoma) is a benign, usually slow growing tumour of the ‘schwann’ cells that make up the lining of the eighth cranial nerve as it passes through a tiny canal that connects the inner ear to the brain. The eighth cranial nerve is responsible for balance and hearing. 

As the tumour expands, it extends into the brain, assuming a pear shape and putting pressure on the nerves and the brain. Sometimes acoustic neuromas can grow on both sides in a genetic condition called neurofibromatosis type 2.

How is it diagnosed?

Acoustic neuroma is usually discovered after the patient complains of symptoms such as hearing loss, balance difficulty or tinnitus. In a few cases the acoustic neuroma has been detected during the investigation of another, possibly unrelated problem, such as may occur if the patient has been involved in an accident.

In rare instances acoustic neuroma may show none of the above symptoms and the patient may only notice some minor symptoms such as facial numbness.

The presence of an acoustic neuroma can be confirmed by the use of sophisticated scanning and imaging techniques.

How is it treated?

Treatment will vary on a number of factors such as size and position of the tumour. Sometimes if the tumour is small or if it is not causing any symptoms, no treatment may be needed. For most people, surgery is the best form of treatment for acoustic neuroma. In many cases the tumour can be completely removed and no further treatment is necessary but hearing loss in the affected ear cannot be avoided for many people.

what is the incidence of Acoustic Neuroma?

The commonly reported incidence of acoustic neuroma is roughly 1 per 100,000 adults per year[1], in industrialised countries although there wide estimates above and below this figure from 1 per 3,500 to 1 per million per year[2]. 

How does this compare with incidences of other types of tumor?

Cancer Type	UK Incidence (per 100,000 per year)
Acoustic Neuroma	1
Lung Cancer	63 [3]
Breast Cancer (females)	134 [4]
Brain & Central Nervous System	8 [5]
Malignant Melanoma	12 [6]

[1] Hardell et al. Vestibular Schwannoma, Tinnitus and Cellular Telephones. Neuroepidemiology 2003; 22: 124-129
[2] Christensen et al. Cellular Telephone Use and Risk of Acoustic Neuroma. American Journal of Epidemiology 2004; 159:277-283
[3] http://info.cancerresearchuk.org/cancerstats/lung/incidence/
[4] http://info.cancerresearchuk.org/cancerstats/breast/incidence/
[5] http://info.cancerresearchuk.org/cancerstats/brain/incidence/
[6] http://info.cancerresearchuk.org/cancerstats/melanoma/incidence/

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Information on Head and Neck Tumour Disease Rates  

Data on rates for diseases included in INTERPHONE has been taken from the WHO World Cancer Report 2008

General

• Overall, tumours of the nervous system account for less than 2% of all malignancies (about 175 000 cases per year worldwide).
   
• The incidence of these tumours tended to increase in most cancer registration areas over the last few decades, most probably because of better reporting by cancer registries and improvement in medical imaging technologies.
   
• The causes of these diseases are largely unknown; the only proven risk factor is exposure to ionizing radiation, such as x-rays.

Gliomas
A type of brain tumour arising in cells of the brain, are relatively rare and classified as astrocytomas (low-grade) and glioblastomas (high-grade). Each year, between 6-8 brain tumours are diagnosed for every 100,000 people in the west while the incidence is lower (about 2-3 per 100,000) in Africa and Asia. Part of the difference may be explained by access to diagnostic imaging.

Meningioma
A type of brain tumour arising in cells that make up the covering around the brain. Meningiomas, make up about 1 in 5 of all brain tumours diagnosed, which equates to less than 2 per 100,000 people.

Acoustic Neuroma (or acoustic neurinoma)
A rare, benign and often slow-growing tumour of the nerve that connects the ear to the brain and it may be detected due to effects on hearing. It has a natural incidence of about 1 per 100,000 of the population.

Parotid (salivary) Gland Tumours
A type of head and neck tumour, are rare and arise in the salivary glands of the jaw. Tumours of salivary glands affect about 1 to 2 per 100,000 of population.
 

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INTERPHONE Funding

Information on funding of INTERPHONE has been taken from the International Agency for Research on Cancer (IARC) May 2010 INTERPHONE Press release:

“The INTERPHONE study was undertaken as a collaborative effort between a number of partner institutions, co-ordinated by IARC. To date, the overall funding assigned to the INTERPHONE study amounts to approx. 19.2 million euro (€). Of this amount 5.5 million € were contributed by industry sources.

Of these 5.5 million €, 3.5 million € were contributed by the Mobile Manufacturers’ Forum (MMF) and the GSM Association (GSMA), each contributing half of that amount, through a firewall mechanism provided by the UICC (International Union against Cancer) to guarantee the independence of the scientists.

Most of the rest of the 5.5 million € came to individual centres from mobile phone operators and manufacturers, for example, through taxes and fees collected by government agencies. Only 0.5 million € (2.5%) of the overall study costs were provided directly by the industry, in Canada and France, under contracts which preserved the independence of the study.

Other funding was provided by the European Commission (3.74 million €) and national and local funding sources (9.9 million € in total) in participating countries.

Additional funding for the extension of the research to younger and older age groups was received directly from mobile phone operators in the UK under contracts which preserved the independence of the study.”

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