May 2006 Features - Obstetrics & Gynaecology - HPV test recommended for cervical cancer

Obstetrics & Gynaecology
HPV test recommended for cervical cancer

The current technique for screening for cervical cancer involves collecting cells by way of a pap smear and examining them under a microscope. Although this method has reduced cervical cancer in countries where it is regularly used, it has several weaknesses.

A new study found that the test for human papillomavirus (HPV), which is present in almost all cervical cancers, is more sensitive than cytology (cell examination) in detecting cervical cancer. The study is published online in the International Journal of Cancer (Overview of the European and North American Studies on HPV Testing in Primary Cervical Cancer Screening – Jack Cuzick, Christine Clavel, Karl-Ulrich Petry, Chris JLM Meijer, Heike Hoyer, Samuel Ratnam, Anne Szarewski, Philippe Birembaut, Shalini Kulasingam, Peter Sasieni, Thomas Iftner, International Journal of Cancer; Published Online: April 3, 2006 [DOI: 10.1002/ijc.21955].
http://www.interscience.wiley.com/journal/ijc

Cytology is currently the gold standard for cervical cancer detection, but it has several limitations: highquality samples must be collected; identifying the cell changes that may lead to cancer is highly subjective; and the method itself is very repetitive, which can further lead to interpretive errors.

Several studies have shown that HPV testing is more sensitive than cytology at detecting cervical intraepithelial neoplasia (CIN), the changes in cervical cells that can lead to cancer.

The current study was an analysis of data from several countries comparing the two methods. Led by Jack Cuzick, PhD, of the Cancer Research UK Department of Epidemiology, Mathematics and Statistics at Queen Mary School of Medicine in London, researchers performed an overview on patient data for more than 60,000 women in the United Kingdom, France, Germany, the Netherlands, the United States and Canada.

They analysed the comparison of HPV testing to cytology both overall and for different age groups. The results showed that HPV testing was very sensitive (96% overall) in all the studies and that this sensitivity was not affected by age of patient. Cytology was substantially less sensitive than HPV testing (53% overall, although results varied widely) but it was more effective in women over 50 than in younger women. HPV testing was less specific for women under 35, but for older women the differences in specificity between the two methods were quite small. Specificity refers to the percentage of people who are disease-free and who test negative. There will always be some people who do not have the disease, but who are positive for the screening test (HPV or cytology).

“While well-conducted screening programmes based on cytology have undoubtedly led to a large reduction of cervical cancer in some countries, the high variability in sensitivity reported here indicates the need for strict quality control,” the authors note.

“HPV testing is highly reproducible, more easily monitored, provides an objective test outcome and can easily be automated.” Since only persistent HPV infections are thought to be associated with precancerous lesions, they suggest that procedures need to be developed for repeat testing to detect infections that may be transient, especially in younger women. They also suggest performing the HPV test as the sole primary test, since it is the more sensitive of the two methods, and follow it with cytology, the more specific test, in those who test positive initially.

A recent statement from the International Agency for Research on Cancer (IARC) concluded that HPV testing could reduce the incidence and mortality from cervical cancer and that it is likely to be at least as effective as cytology.

The English Cervical Screening Advisory Committee has recently accepted the IARC statement and agreed that the HPV test could be used by the national screening programme.

“These statements should be influential in establishing streamlined large-scale demonstration projects employing HPV testing as part of primary screening,” the authors conclude.

“Such projects are needed to determine how best to implement this new test, and to see if it can reduce invasive cancer rates below those now achieved with cytology-based programmes.”

HPV vaccinations expected soon

A report from the 4th International Conference on Teenage and Young Adult Cancer Medicine in London on 30 March says parents of young girls may soon be offered the opportunity to have their daughters immunised against a sexually transmitted virus that is the major cause of cervical cancer.

Professor Henry Kitchener told the conference that progress in developing vaccines against the human papillomavirus (HPV) had reached a stage where they were soon to be submitted for licensing. But he warned that it was important there were programmes of education for women and men, particularly parents, about HPV and cervical cancer. Professor Kitchener, of the Academic Unit of Obstetrics and Gynaecology at the University of Manchester, UK, said: "It is vital that people understand the context in which HPV vaccination is being proposed and that they realise that it is not a treatment for the virus once it has been contracted, or for cervical cancer if the disease has started to develop. Vaccination should not be misconstrued as a green light for sexually permissive behaviour – rather, it is an effective means of preventing HPV infection when young women are most susceptible in their teenage and young adult years.

“The origins of cervical cancer lie in HPV infection of the cervix, a sexually transmitted infection most frequently acquired by women shortly after they start sexual activity. In a minority of women, the HPV infection persists and may result in pre-cancerous changes; these can develop into cancerous changes in these women, particularly if they are unscreened. Testing for HPV infection is becoming talked about more, as is the potential of vaccination. In particular, there are two types of HPV, types 16 and 18, at which vaccine research is being directed. HPV 16 and 18 are thought to be responsible for 70% of cervical cancers worldwide.

“If the current vaccinations that are being developed are approved for use, then they could be used to vaccinate girls at puberty in order to prevent HPV infection. By preventing HPV infection, this could have the effect of preventing the pre-cancerous and cancerous changes that HPV infection can trigger. Women and men need to be more aware of HPV infection and what it may mean. Parents who may be asked to consent to their children being vaccinated need to be aware of these important issues.” There are nearly 500,000 new cases of cervical cancer diagnosed each year worldwide, and every year nearly 274,000 women die from the disease, with about 80% of these deaths occurring in developing countries where there is little or no access to cervical screening programmes.

“HPV vaccination has the potential to make a huge difference to women's lives, particularly in developing countries,” said Professor Kitchener. “Cervical cancer is a major killer of women worldwide. It is not only one of the largest causes of death due to cancer, but is also responsible for a great deal of suffering. Tragically, its regions of highest incidence are those in which preventative screening cannot be provided due to lack of resources, and those least well equipped to treat the condition for the same reason.

“In more affluent well developed countries, cervical screening by means of cytology has become an established strategy for identifying women at risk of developing cervical cancer and has been responsible for a dramatic fall in incidence and death rates. Vaccination programmes will still require some form of screening to be in place either for unvaccinated women or for women who develop an HPV infection despite the vaccination. Falling death rates have also been due to improved forms of treatment for advanced disease, principally in the form of concomitant chemotherapy and radiotherapy.”

Professor Kitchener concluded: “HPV vaccines provide hope for major international programmes of primary prevention.”

Database to facilitate treatment of infertility

Infertility is a growing problem in society. The number of embryo transfers performed in Europe (the last human-controlled step of the in-vitro fertilisation technique) increased by 8% between 1999 and 2003. Recent studies confirm this rising trend.

Despite the advances in IVF and other assisted reproduction technologies (ART), only 25% of embryo transfer attempts will lead to a successful pregnancy. In the remaining 75% of cases, the embryo fails to implant into the mother’s uterus. In many cases this may be due to the embryo being ‘rejected’ by the mother’s immune system. The way in which “rejection” is avoided when an embryo implants successfully and what goes wrong when it fails to implant are poorly understood.

“The answers to these questions are crucial for the treatment of infertility” says Professor Ian Sargent, of the University of Oxford and member of EMBIC, a network of excellence comprising more than 200 researchers and clinicians across Europe. The organisation, supported by the European Commission, aims to understand the molecular mechanisms involved in the control of embryo implantation.

To try to resolve this problem, EMBIC has launched a database on human infertility. Member laboratories will analyse the results of both basic research and clinical data.

“By combining these observations (basic and clinical), we will be able to develop better treatment protocols in the future” declared Dr Nathalie Lédée of the Université de Versailles Saint Quentin en Yvelines and the person responsible for the EMBIC Database on Human Infertility. The studies that are being carried out require access to large numbers of clinical samples that could never be collected in one IVF unit or hospital working in isolation. Only by a joint international effort will we be able to produce the results that we need.”

The EMBIC database will be located in France and will bring together, anonymously and coded, the clinical information of fertile and infertile volunteers from eight IVF centres from seven European countries. EMBIC scientists will complete this information by entering into the database the results of the tests carried out on these samples, using the latest technologies for molecular and cell biology.

“The strength of EMBIC is that by working together, large numbers of samples can be collected in a short space of time. It also allows direct comparisons between different treatments carried out in different countries across Europe,” says Prof Sargent. The EMBIC scientists are convinced that this shared effort “will provide new insights into the causes of infertility and will lead to novel, targeted treatments for this very distressing condition”.

For more information visit: www.embic.org