Team:WITS-South Africa/The Problem

       http://home.ncifcrf.gov/ccr/flowcore/cervical_cancer_ribbon4.GIF

[http://www.cansa.org.za/cgi-bin/giga.cgi?cat=1313&limit=10&page=0&sort=D&cause_id=1056&cmd=cause_dir_news To find out more about HPV and cervical cancer click here!]

Public enemy: Human Papillomavirus-induced disease

Cervical cancer is the second most prevalent cancer in women worldwide and the cause of 250 000 deaths every year Human Papillomavirus (HPV) has been established as the etiological agent of cervical cancer (100% of cases = HPV DNA) HPV is a sexually transmitted infection – the most common STI in the world! Its ubiquity is due to the fact that it is mainly asymptomatic in men and its effects are only seen long after initial infection in women

What is HPV? And how does it cause disease?

HPV is a ds DNA virus which is highly host and tissue specific It infects non-keratinised, stratified squamous epithelium (mucosal skin cells with a high rate of cellular turnover) Over 100 strains of the virus exist, some of which have been implicated in 100% cervical cancer (high-risk strains such as type 16 and 18) or cancers of the vulva, vagina, penis, anus, and head and neck (tongue, tonsils and throat) Other strains cause infectious but benign genital warts

In most cases the body’s immune system recognises the infection and is able to clear it effectively Most women who have been infected with HPV will never even realise it However, HPV has developed methods of evading the immune system, including decreased antigen presentation and blunting of the interferon response In some individuals, this results in the progression of cancer Immunocompromised individuals are much more likely to be susceptible. Risk factors such as smoking and fertility rate also contribute

Let’s talk about South Africa… HPV is especially problematic in the developing world where access to regular health care is limited, such as South Africa In South Africa current estimates indicate that every year 5743 women are diagnosed with cervical cancer and 3027 die from the disease. About 21% of women in the general population are estimated to harbour cervical HPV infection at a given time Early detection and careful monitoring of disease progression is vital and this is often not possible for women living in rural or under resourced areas WHO guidelines recommend that all women aged 18 – 69 have a pap smear every three years. Only 13.6% of women in South Africa are being screened for cervical cancer according to these guidelines

Detection and diagnosis There is no antiviral or cure for HPV infection The only diagnostic for HPV does not detect the virus itself and will only detect an infection if it has actually progressed to cancer! This is the PAP smear - a histological investigation which looks for abnormal cell morphology which arise long after the initial HPV infection as a result of virally-induced oncogenic events A smear can detect the pathology very (too) late PCR can also be used to detect viral DNA – this is the current gold standard for HPV diagnosis but is strain specific and impractical to implement on a wide scale at this point

Our Machine

The development of a whole-cell biosensor for the immediate, in vivo detection of Human Papillomavirus (HPV), in the form of an engineered commensal vaginal bacterium. This mechanism would be safe, low-cost and easily administrable; and is intended primarily for women in resource-poor settings.

The link between HPV and cervical cancer is well-established. Although much progress has been made in developing a vaccine, the vaccines that are currently available have some limitations (mainly due to high cost and inadequate accessibility) in their ability to prevent disease burden in developing countries, where 80% of cervical cancer deaths occur annually.

This inspired the search for a method of detecting the virus that will alert the infected individual in a discreet yet persistent manner. The machine would also have the potential to be further adapted to have the ability to neutralise the virus and prevent the infection from spreading. Basically, the machine that we wish to design will be able to detect an infectious agent and inform neighbouring bacteria - as well as the host - as to the presence of that pathogen.