Cervical cancer - On the horizon

A number of exciting developments are being evaluated for the screening, imaging and treatment of cervical cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body.. The following are covered on this page:

p16 testing

Despite the recent introduction of human papilloma virusA sexually transmitted virus that can cause genital warts and may also have a role in the development of various cancers. immunisation (HPV vaccine) for the prevention of cervical cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. in several countries, screening for this condition is still important.

What is it?

p16 is a protein that has been shown to accumulate in abnormal cells infected with high-risk strains of human papilloma virusA sexually transmitted virus that can cause genital warts and may also have a role in the development of various cancers., the virusA microbe that is only able to multiply within living cells. that increases the risk of cervical cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body..1

How does it work?

Samples from both cervical screening tests and biopsies can be tested for p16. Testing for this protein could improve current methods of cervical cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. screening in both high and low income countries.1,2

Who is it for?

Testing for p16 may help to identify women with low-grade cervical lesions (CIN1) who would benefit from closer follow-up than they might otherwise have been given.2

What stage of development has it reached?

Studies so far show that high levels of p16 are associated with abnormal cervical cells. Larger studies are needed, however, to evaluate the role of p16 testing in practice.1,2

Positron emission tomography

What is it?

Positron emission tomography (PET) is an imaging technique that gives information on how the body is functioning, rather than simply showing an anatomical image.8

How does it work?

PET scanning involves the intravenous injection of a radioactive substance, after which a scan can reveal how this substance has been distributed in the body.3

PET scanning has already been found to be useful in assessing several different types of cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body.. Recently it has been suggested that this technique may also be valuable in cervical cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body..4

While computed tomography (CTA scan that generates a series of cross-sectional X-ray images.) and magnetic resonance imagingA technique for imaging the body that uses electromagnetic waves and a strong magnetic field. (MRIAn abbreviation for magnetic resonance imaging, a technique for imaging the body that uses electromagnetic waves and a strong magnetic field.) give information on tumour size and the stage of disease, they are not as accurate in assessing any spread of the tumour to lymph nodesSmall swellings along the lymphatic system that filter lymph, a fluid derived from the blood, and produce antibodies and a type of white blood cells, lymphocytes.. PET scanning gives extra information by assessing the metabolic activity of the tumour.4

Who is it for?

PET scanning may be more useful in people with later-stage disease.4

What stage of development has it reached?

PET is already a widely accepted imaging technique, and it seems to have an expanding role in cervical cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body.. Early reports suggest that PET scanning can help with the staging of cervical cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. and assessing the response to treatment.4

Image-guided adaptive brachytherapy

Internal radiotherapy, also known as brachytherapyA type of radiotherapy where radioactive pellets or wires are inserted into the tumour., is a way of delivering radiation directly into the site of a tumour. A source of radioactivity is placed close to the tumour, so that a high dose of radiotherapy can be delivered to the tumour while surrounding normal tissues are exposed only to a lower dose. A newer type of brachytherapyA type of radiotherapy where radioactive pellets or wires are inserted into the tumour. is being assessed for cervical cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body.: image-guided adaptive brachytherapyA type of radiotherapy where radioactive pellets or wires are inserted into the tumour..

What is it?

Brachytherapy is usually based on two-dimensional X-rayA type of electromagnetic radiation used to produce images of the body. images. Image-guided adaptive brachytherapyA type of radiotherapy where radioactive pellets or wires are inserted into the tumour. is a newer type of brachytherapyA type of radiotherapy where radioactive pellets or wires are inserted into the tumour. that uses cross-sectional imaging, mainly magnetic resonance imagingA technique for imaging the body that uses electromagnetic waves and a strong magnetic field. (MRIAn abbreviation for magnetic resonance imaging, a technique for imaging the body that uses electromagnetic waves and a strong magnetic field.). This allows a three-dimensional view.5

How does it work?

It is thought that looking at the tumour in relation to the source of radioactivity and surrounding organs at the time of brachytherapyA type of radiotherapy where radioactive pellets or wires are inserted into the tumour. will allow the radiation dose to be adapted and help to spare the healthy surrounding tissues from radiation.6

This more precise way of delivering brachytherapyA type of radiotherapy where radioactive pellets or wires are inserted into the tumour. can improve outcomes while lowering side-effects from treatment.5

Who is it for?

This technique is mainly used for cervical cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. that has spread locally.6

What stage of development has it reached?

A large clinical trial is under way to test positive early findings. The International study on MRIAn abbreviation for magnetic resonance imaging, a technique for imaging the body that uses electromagnetic waves and a strong magnetic field.-guided brachytherapyA type of radiotherapy where radioactive pellets or wires are inserted into the tumour. in locally advanced cervical cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body., or EMBRACE study, started in 2008.5

At the moment, very few treatment centres use this therapy routinely.5

Targeted therapy

Pharmaceutical treatments for people with advanced cervical cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. are limited at present. However, researchers are looking at new, targeted therapies.7

What is it?

Two promising targets for therapy being evaluated are the epidermal growth factorA chemical that stimulates new cell growth and maintenance in the body. receptor (EGFR) and the vascular endothelial growth factorA chemical that stimulates new cell growth and maintenance in the body. (VEGF) signalling pathways. These pathways have important roles in the growth of the tumour and the formation of the bloodA fluid that transports oxygen and other substances through the body, made up of blood cells suspended in a liquid. vessels that supply it.7

Researchers are looking at several medications that target these pathways. Two potential new treatments are cetuximab, which targets EGFR, and bevacizumab, which targets the VEGF signalling pathway.7

How does it work?

Studies have shown that people who have cervical cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. have higher levels of EGFR. Blocking EGFR has been shown to improve the response of tumours to chemotherapyThe use of chemical substances to treat disease, particularly cancer. and radiotherapy treatment.7

VEGF is one of the major pathways involved in bloodA fluid that transports oxygen and other substances through the body, made up of blood cells suspended in a liquid. vessel formation in cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body., and its activity is associated with tumour progression and worse outcomes in cervical cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body..7

Who is it for?

A number of studies are looking at the use of these therapies alone or in combination with chemotherapyThe use of chemical substances to treat disease, particularly cancer. or radiotherapy in people with early, advanced or recurrent cervical cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body..7

What stage of development has it reached?

Several phase I and II clinical trials of these, and other, targeted therapies are in progress at the moment.7

Robotic surgery

Surgical techniques are continually being updated and evaluated. Open abdominal surgery is the method most often used for radical hysterectomyThe surgical removal of the uterus (womb).. Laparoscopic surgery is a newer approach, which is less invasive. However, this approach has limitations, which robotic surgery may help to alleviate.

What is it?

Robotic surgery is a new technology that is designed to address many of the problems of laparoscopic hysterectomyThe surgical removal of the uterus (womb).. Recently, robotic surgery has started to become more accepted in treating gynaecological cancers, and a few small studies have been published, though findings from larger studies are still awaited.8

How does it work?

During robotic surgery, the surgeon sits at a monitor and uses a viewer, hand controls and foot pedals to control surgical instruments. The benefits of robotic surgery compared with laparoscopyKeyhole surgery that uses an instrument called a laparoscope to examine the abdominal organs. include a three-dimensional view, greater freedom of movement and greater precision.8,9

Early findings suggest that this approach may reduce bloodA fluid that transports oxygen and other substances through the body, made up of blood cells suspended in a liquid. loss, and lessen the need for pain-medication after the procedure.8

Who is it for?

Radical hysterectomy is a treatment for people with early-stage cervical cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. (stages I and II) - whether it is done by a traditional, abdominal approach or by a newer approach such as robotic surgery.9

What stage of development has it reached?

Robotic technology is developing quickly, but can be expensive. Like any new approach, it is important that it is properly reviewed and evaluated before becoming standard. So far, this procedure has been evaluated only in small groups of patients.8,9

Total mesometrial resection

What is it?

Total mesometrial resection The surgical removal of part of the body.(TMMR) is a new approach to performing radical hysterectomyThe surgical removal of the uterus (womb).. It is hoped that this technique will reduce the risk of complications and of the cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. coming back.10

How does it work?

TMMR is a modified version of traditional radical hysterectomyThe surgical removal of the uterus (womb).. It removes tissue based on improved knowledge of where the cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. is most likely to spread. It aims to prevent damage to the nerveBundle of fibres that carries information in the form of electrical impulses. supply to the bowel, bladderThe organ that stores urine. and vagina.

Who is it for?

The new technique is for women with early-stage cervical cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body..

What stage of development has it reached?

The technique has been tested in women with early stage cervical cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. and the researchers have called for further evaluation of TMMR in multi-centre controlled trials.

Dietary supplement

What is it?

It is an approach that uses a dietary supplement called diindolylmethane (DIM) to treat abnormal cervical cells.

How does it work?

DIM is found in cruciferous vegetables like broccoli, Brussels sprouts, cauliflower, cabbage, and kale. It is a type of plant chemical called an indole. UK researchers are investigating whether a supplement of DIM can reduce the incidenceThe number of new episodes of a condition arising in a certain group of people over a specified period of time. of cervical abnormalities. Cervical screening can pick up abnormal cells on the cervixAny neck-like structure; most commonly refers to the neck of the uterus.. DIM may help the cells of the cervixAny neck-like structure; most commonly refers to the neck of the uterus. return to normal in women who show borderline or mild cellThe basic unit of all living organisms. changes.

Who is it for?

Women who show borderline or mild cellThe basic unit of all living organisms. changes in cervical screening.

What stage of development has it reached?

The dietary supplement is currently being assessed in clinical trials.11

References: 
  1. Gravitt PE, Coutlée F, Iftner T, et al. 'New technologies in cervical cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. screening.' Vaccine. 2008; 26S(2): K42-K5.
  2. p16INK4a immunostaining in cytological and histological specimens from the uterine cervixAny neck-like structure; most commonly refers to the neck of the uterus.: A systematic review and meta-analysis. Tsoumpou I, Arbyn M, Kyrgiou M, et al. Cancer Treatment Reviews. 2009;35:210-20.
  3. Banerjee AK. 'Radiology made easy.' 2006; 2nd edition: 5-6.
  4. Magne&acuteHas a sudden onset.; N, Chargari C, Vicenzi L, et al. 'New trends in the evaluation and treatment of cervixAny neck-like structure; most commonly refers to the neck of the uterus. cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body.: The role of FDG-PET.' Cancer Treatment Reviews. 2008; 34: 671-81.
  5. Pötter R, Kirisits C, Fidarova EF, et al. 'Present status and future of high-precision image guided adaptive brachytherapyA type of radiotherapy where radioactive pellets or wires are inserted into the tumour. for cervixAny neck-like structure; most commonly refers to the neck of the uterus. carcinomaA malignant tumour (cancer) that is formed from the epithelium, the tissue that covers the open surfaces of the body..' Acta Oncologica. 2008; 47: 1325-36.
  6. Potter R, Fidarova E, Kirisits C, et al. 'Image-guided adaptive brachytherapyA type of radiotherapy where radioactive pellets or wires are inserted into the tumour. for cervixAny neck-like structure; most commonly refers to the neck of the uterus. carcinomaA malignant tumour (cancer) that is formed from the epithelium, the tissue that covers the open surfaces of the body..' Clinical Oncology. 2008; 20: 426-32.
  7. Campo JM, Prat A, Gil-Moreno A, et al. 'Update on novel therapeutic agents for cervical cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body..' Gynecologic Oncology. 2008; 110: S72-6.
  8. Zakashansky K, Bradley WH and Nezhat FR. 'New techniques in radical hysterectomyThe surgical removal of the uterus (womb)..' Curr Opin Obstet Gynecol. 2008; 20: 14-9.
  9. Ramirez PT, Soliman PT, Schmeler KM, et al. 'Laparoscopic and robotic techniques for radical hysterectomyThe surgical removal of the uterus (womb). in patients with early-stage cervical cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body..' Gynecologic Oncology. 2008; 110: S21-4.
  10. Höckel M, Horn LC, Manthey N, et al. 'Resection of the embryologically defined uterovaginal (Müllerian) compartment and pelvicRelating to the pelvis. control in patients with cervical cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body.: a prospective analysis.' The Lancet Oncology. 2009; 10(7): 683-92.
  11. 'Diindolylmethane in treating patients with abnormal cervical cells'.  Clinical Trials.gov. HYPERLINK "http://clinicaltrials.gov/ct2/show/NCT00462813" accessed 22 October 2009.