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HPV vaccines: weapons against cervical cancer

Nicola O'Connell
BA(Hons)
Freelance Healthcare and Medical Writer
London

Surrounding the excitement there are nevertheless a number of questions that remain to be answered, such as who exactly will receive the vaccine, who will still need to have cervical smears and how long will the protection last? And how will the vaccines alter cancer rates compared with the National Cervical Screening Programme?
In many cases, only time will tell. "Screening still needs to continue for a while yet, because we don't know how long the immunity lasts. But girls born today may not need to have smears," says Dr Anne Szarewski, clinical consultant at Cancer Research UK.
Both vaccines protect against human papillomavirus (HPV) types 16 and 18, which together account for 70-80% of cervical cancers.(1) It has now been shown that 99.7% of cervical cancers contain HPV DNA.(2)
HPV is a very common infection, infecting approximately 75% of sexually active women at some point in their lives.(3) "By their early twenties, 20-25% of men and women have HPV in their genital tract, and this figure increases by middle age," says Dr Ian Duncan, research and honorary consultant gynaecological oncologist at the University of Dundee. "Within six to 18 months of exposure, 90% of people develop immunity to that HPV. But of those 10% who do not, a further 10-20% are seriously at risk."
Cancer Research UK suggests that there are a number of risk factors that increase a woman's likelihood of developing cervical cancer. These include: smoking, poor diet, a weakened immune system, "the Pill", numerous sex partners and having sex at a young age.

Promising trial results
Experts have been impressed with the trial results of both HPV vaccines (Cervarix from GlaxoSmithKline and Gardasil from Sanofi Pasteur MSD's/Merck & Co). "Both companies have pushed forward their applications for the vaccines because they look so promising," says Dr Tito Lopes, consultant gynaecological oncologist at Queen Elizabeth Hospital, Tyne and Wear. "Both vaccines appear to have prevented persistent infection in certain HPV types and to have reduced the risk of premalignant condition cervical intraepithelial neoplasia (CIN)."
In clinical trials, Cervarix demonstrated 100% protection against persistent infection with HPV 16 and HPV 18, and protection from related precancerous lesions.(4) Preliminary evidence of broader protection against some other cancer-causing strains of HPV, in addition to HPV 16 and 18, was also shown. The vaccine is formulated with the proprietary innovative AS04 adjuvant, which has been demonstrated in clinical trials to induce a stronger antibody response against HPV types 16 and 18, compared with the same vaccine formulated with aluminium alone.
Gardasil is designed to protect against HPV types 16 and 18 as well as genital warts (types 6 and 11). Data show that the vaccine prevents 100% of high-grade cervical precancerous and noninvasive cervical cancers, as well as significantly reduces the combined incidence of persistent HPV 6, 11, 16 and 18 infections and related disease.
Dr Szarewski says: "It is thought that the vaccines will be most effective if given to girls who have not yet been infected with HPV, so young girls will probably be the first to receive them. But further trials will show how effective the vaccines are in older women, too.
"I think that it is also helpful that the two vaccines differ, because there will be some women, in some cultures, who will not want to be associated with genital warts, whereas they may accept a vaccine that solely protects against cervical cancer."

Screening: a victim of its own success?
Questions will undoubtedly be raised about whether the vaccines can match the success of the screening programme. Before the introduction of the National Cervical Screening Programme in 1988, the incidence of cervical cancer in England and Wales had been rising steadily among women under the age of 35. But the incidence fell by 42% between 1988 and 1997, which is directly related to the screening programme.(5)
Liquid-based cytology (LBC), the newer method of preparing cervical samples for cytological examination, represents an important advancement in screening. LBC involves using a thin brush-like device, rather than a spatula, to collect cells. The head of the brush is rinsed or broken off into a vial of preservative fluid so that the cells are better preserved, leading to more reliable results.
The three pilot hospitals that tested LBC (Southmead Hospital in Bristol, Royal Victoria Infirmary in Newcastle and Norfolk and Norwich Hospital) had repeat smear rates of 1-2%, compared with 9% when smears are put straight onto slides.(6) These hospitals are now continuing to use LBC and the NHS plans to roll out LBC nationally, but this is likely to take about five years.
Yet encouraging women to have smears still remains a challenge, particularly as uptake of the screening programme is starting to fall. Recent figures from the Office for National Statistics reveal that coverage of the screening programme is decreasing, with a 5% drop among 25-29-year-olds - the group most at risk - during the last five years. Overall, one in five eligible women do not participate in the screening programme.
"In a way the screening programme is a victim of its own success. As the incidence of cervical cancer has dropped, so has the fear. We just don't tend to hear about the disease very much anymore," says Norma Evans, specialist nurse in vaccines and immunisations, based in Cheshire.

Anxiety and distress associated with smears
Complacency may be one reason why women are not coming forward for screening, but there is also evidence to suggest that they are anxious about the overall procedure. When 400 women throughout Northern Ireland completed a questionnaire designed to measure their cancer-screening behaviour, it was found that the most important predictor of attendance for cervical smears was lack of fear of the consequence of the investigation.(7)
Another survey, undertaken in New York City, demonstrated women's concerns over receiving an "abnormal" smear result. One of the most consistent findings of the study was a high degree of distress. Women who associated abnormal results with cancer and believed themselves to be at personal risk were frightened.(8) Women were also dissatisfied with communication methods, as many said that after receiving a letter they were unsure of what they were supposed to do.
Women's different experiences associated with cervical smears are the focus of "The Cervical Monologues", a Women & Theatre production that received funding from the Women's Nationwide Cancer Control Campaign. The production has been performed at different locations throughout the UK and was also held at the RCN Congress and Exhibition 2006 in April. The script is based on in-depth interviews with women and health professionals living and working in Birmingham.
The series of monologues reflects people's own experiences, and demonstrates the anxiety suffered by some women. A number of women did not understand the purpose of the smear, and others did not perceive it was necessary. These views contrasted with those of healthcare professionals, who sometimes appeared not to fully appreciate the women's need for clear communication, or to understand the emotions associated with the process.

Need for education
Without attempting to scare women, there appears to be a definite need to remind women about the risks of cervical cancer and the role of screening as a preventive measure. Cervical cancer remains the second most common cancer in women under the age of 35, according to Cancer Research UK, and 2,800 women in the UK are diagnosed with cervical cancer each year. In 2003, 1,098 deaths from cervical cancer were registered in the UK.
Norma Evans says: "We need to find ways to get messages across about cervical cancer. The launch of the vaccines will be excellent and exciting news - and it will also enable us to once again highlight cervical cancer. Most practice nurses are very good at communicating with patients, so we all need to work together about how best to educate the patients. The vaccine launch should help to get cervical cancer back on the map."

Conclusion
The forthcoming launch of the two new HPV vaccines signifies a new era in the fight against cervical cancer. Further trials on women of different age groups are now being conducted - and if successful, use of the vaccines could be very widespread. Nevertheless, it is too early to speculate on how long cervical cancer screening will need to continue, even if ultimately - perhaps in 20 years time - it may no longer be necessary. Screening has played a monumental role in reducing the incidence of cervical cancer, and for the time being,the new vaccines are likely to complement the screening programme.
As awareness of cervical cancer and the benefits of screening are not particularly high among the general population, women need to be educated about the disease and the role of screening. The launch of the vaccines provides the ideal opportunity to do this, and nurses could be key communicators.

References

  1. Szarewski A. Prophylactic vaccines for human papillomavirus: a bright future for cervical cancer prevention. J Med Screen 2005;12(4):163-5.
  2. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999;189(1):12-19.
  3. Choma KK. ASC-US and HPV testing. Am J Nurs 2003;103(2):42-50.
  4. Harper DM, Franco EL, Wheeler C, Ferris DG, Jenkins D, Schuind A, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women:a randomised controlled trial. Lancet 2004;364:1757-65.
  5. National Statistics. Health quarterly statistics 7. Autumn 2000. Available from: http://www.statistics.gov.uk/downloads/theme_health/HSQ7Book.pdf
  6. NHS. Liquid based cytology (LBC): NHS cervical screening programme. Available from: http://www.cancerscreening.nhs.uk/cervical/lbc.html
  7. Murray M, McMillan C. Health beliefs, locus of control, emotional control and women's cancer screening behaviour. Br J Clin Psychol1993;32(Pt 1):87-100.
  8. Karasz A, McKee MD, Roybal K. Women's experiences of abnormal cervical cytology: illness representations, care processes, and outcomes. Ann Fam Med 2003;1(4):196-202.

Resources
European Cervical Cancer Association
W:www.ecca.fr/en/
NHS Cancer Screening Programme
W:www.cancerscreening.nhs.uk/cervical/index.html
Cancer Research UK
W:www.cancerresearchuk.org/aboutcancer/specificcancers/cervicalcancer?vers...