Trials update in wales
Authors: Fiander A. 
Published: September 2007

Three ongoing studies will be presented and discussed.

Prevalence of Human Papillomavirus Infection in a South Wales Screening population

Methods: A total of 10 000 consecutive, anonymous liquid based cytology screening samples were collected over a five month period in 2004. Age, cytology result and social deprivation score was provided for each specimen. The methodology was chosen to ensure inclusion of all women attending routine cervical screening, avoiding potential constraints associated with obtaining individual informed consent.

The liquid based cytology samples were processed and reported by the receiving cytology laboratory and the residual specimens sent to the HPV Research Laboratory, Wales College of Medicine, where they were processed and stored at ‐80°C until analysis. High risk and low risk HPV Typing was undertaken using PCR – EIA (Jacobs et al 1997). Full high risk typing was performed on HPV positive specimens.

Results: The study population had a mean age of 38 years with 92% negative, 5% borderline and 3% dyskaryotic cytology. The average social deprivation score was 17.4 (based upon the Welsh Index of multiple deprivation).

The following results will be presented:

 HPV prevalence by age.

 HPV prevalence by cytology result.

 Type specific HPV prevalence in single and multiple infection.

Conclusion: This study represents the largest type specific HPV Prevalence Study in the UK to date. As such it will form a useful base line against which to access performance of marketed HPV tests and evaluating the impact following implementation of HPV vaccination.

[Funded by Welsh Office for Research and Development]

CRISP – 1 Study (Cervical Randomized Intervention Study Protocol ‐1)

Background: Indole‐3‐carbinol (I3C) and Diindolylmethane (DIM) are found in cruciferous vegetables and have been identified as compounds that could potentially prevent or halt carcinogenesis. I3C spontaneously forms DIM in vivo during acid digestion. I3C has been shown to prevent the development of cervical cancer in HPV 16 transgenic mice and both I3C and DIM have been shown to promote cell death in cervical cancer cell models. DIM is the major active bi‐product of I3C and preliminary data indicate that DIM is active in cervical dysplasia and may be better tolerated than I3C.

Aim: To investigate chemoprevention of high grade cervical neoplasia using Diindolylmethane (DIM) supplementation in women with low grade cytological abnormalities on cervical cytology.

Objectives: To observe any reduction in the prevalence of histological proven high‐grade cervical intraepithelial neoplasia (CIN) after 6 months of supplementation.

• To observe any reduction in the prevalence of cytological abnormalities.

• To observe any changes in the clinical appearance of the cervix.

To assess acceptability and monitor any side effects of DIM supplementation.

• To assess whether any benefit is seen in relation to Human Papillomavirus (HPV) status including HPV Type, Viral load and integration.

Methods: This is a double blind randomized placebo‐controlled trial involving 600–700 women with low grade cytological abnormalities on a cervical smear. Randomization is in the ratio of 2 : 1 in favour of active medication. Women with first mildly dyskaryotic smear or second borderline smear are eligible. They are asked to take two capsules daily for 6 months. At the end of 6 months they undergo repeat cervical cytology, HPV testing and colposcopy.

Results: A progress report will be given for this ongoing study.

[Funded: ‐ Cancer Research UK]

Type Specific HPV Infection in Welsh Cervical Cancers

Background: Whilst there have been numerous studies of HPV infection associated with cervical cancer and on prevalence of Human Papillomavirus in diverse populations there have been no studies of these variables in the same population. Against a background of prophylactic HPV vaccination it is important to assess potential protection against cervical cancer within a given population.

The most comprehensive analysis of HPV type specific cervical cancer is a meta‐analysis published by the IARC in 2003. This however included only three UK based studies, totalling 118 cases, 75 of which were only investigated by HPV type PCR for four high risk types. None of this data was presented with associated population based prevalence data. Therefore, the research objectives for this study in combination with the first study above, are as follows:

To determine the frequency of specific HPV types in cervical cancers in Wales.

To compare the distribution of specific HPV types amongst cervical cancers with their prevalence in the general population.

This will allow accurate delineation of the relationship between prevalence of specific HPV types in the general population and their association with clinically relevant disease. This information is a pre‐requisite to assess the potential impact of prophylactic vaccination against HPV infection in Wales.

Methods: Welsh Cervical Cancer specimens from 2000–2005 will be identified from pathology departments within Wales. The pathology of each tumour will be reviewed by a single Gynaecological Pathologist. The age of the patient and pathological features of the tumour will be noted. DNA will be extracted from the paraffin sections and HPV typed by PCR‐EIA.

Results: A progress report will be given for this ongoing study.

[Funded by Welsh Office for Research and Development]