HPV vaccination: An opportunity for good and the potential for harm

On 20 June 2007, The Department of Health announced that following expert advice from the Joint Committee on Vaccination and Immunisation (JCVI), there was agreement in principle to the introduction of a vaccine against human papillomavirus (HPV) (Salisbury 2007). Details of the programme will be finalised over the next few months following further advice from the JCVI, including a cost benefit analysis. The precise nature of the final programme will be important because it is at once an opportunity for health gain but also a potential threat to the existing successful National Health Service cervical screening programme (NHSCSP). Cancer of the cervix is the second most common female cancer worldwide. Each year just under half a million women are diagnosed with the condition and just over a quarter of a million die from it (Ferlay et al. 2004). Most of the deaths occur in developing countries. In countries which have introduced population based screening programmes there has been a significant reduction in the incidence of and mortality from the disease. In the UK, there has been a 7% year-on-year reduction in the incidence of cervical cancer since the introduction of the formal call and recall programme in 1988 (www.cancerscreening.nhs.uk; Peto et al. 2004). It is now recognised that squamous cancer of the cervix is caused by certain high risk types of the human papillomavirus (Walboomers et al. 1999). Recently, prophylactic vaccines have been produced against some of the HPV types associated with lower genital tract disease (Inglis et al. 2006). The ability to vaccinate large population groups against a virus that causes a significant number of cancer cases and deaths is an exciting possibility. However, within a developed country with an established, successful cervical screening programme, there is somewhat surprisingly, the potential for harm if the introduction of the vaccination programme is not carefully planned. In England, it is currently accepted that 75% of deaths from cervical cancer are avoided as a result of the successful National Health Service cervical screening programme (www.cancerscreening.nhs.uk). Women aged 25 – 50 years are invited 3-yearly and women aged 50 – 65 years are invited every 5 years to undergo a cervical smear. Traditionally, this was using conventional cytology but increasingly, liquid based cytology (LBC) is being employed. The estimated cost of the programme is £150 million per annum. About 9% of smears require some form of further investigation, about 120,000 women are referred for colposcopy and about 90,000 undergo treatment for cervical intraepithelial neoplasia, with 95% first time treatment success rates and 2 – 3% side-effects from treatment (www.cancerscreening.nhs.uk; Luesley and Leeson 2004). The success of the programme has been achieved by high coverage rates of the target population with 73% of women having undergone a smear test in the last 5 years (www.cancerscreening.nhs.uk). Programmes with poor coverage rates often have little effect on significant disease prevalence. There are over 130 different HPV types, of which about 20 affect the lower genital tract. HPV 6 and HPV 11 are associated with the development of condylomata acuminata (genital warts), and HPV 16 and HPV 18 are the two types responsible for about 70% of cases of invasive cervical cancer worldwide (De Villiers et al. 2004; Munoz et al. 2003) HPV 16 is also associated with some cases of vulval, penile, and anal cancer (Madeleine et al. 1997). Two companies have produced HPV vaccines. Merck have produced a quadrivalent HPV 6/11/16/18 virus-like particle vaccine with amorphous aluminium hydroxyphosphate sulphate (Gardasil, Merck), and GlaxoSmithKline, a bivalent HPV 16/18 virus-like particle vaccine adjuvanted with AS04 (Cervarix, GSK; Inglis et al. 2006). Initial placebo-based studies have confirmed several important facts. First, the serocoversion rate for the development of neutralising antibodies against the relevant HPV types is high, with antibody levels reaching significantly higher levels than those achieved following natural exposure to HPV (Giannini et al. 2006). Second, sideeffects are uncommon with no serious events and local site reactions the commonest minor complaints. The level of protection against the subsequent development of HPV carriage and in particular the development of CIN due to the specific vaccinated HPV types is very high (FUTURE II Study Group 2007). This suggests a great potential health gain for a programme involving vaccination of pre-sexually active adolescent females. The FUTURE II