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International Primary Care Association

Clinical Focus Primary Care

The psychosocial effects of HPV-related disease may be related to the disease itself, its treatment and the knowledge that the disease is caused by HPV, a sexually transitted infection. There are also psychosocial consequences from the cervical screening programme, even among women who do not have disease.

Genome structure

The papillomavirus particle or virion consists of a protein coat encapsidating a circular DNA molecule about 8000 base pairs (8kb) in size. The genome can be divided into three domains. The first is a short stretch of DNA (the length differs between different HPV types) known by various names – the non coding region, NCR, the long control region, LCR, or the upstream regulatory region, URR. As these names indicate this region does not encode any genes but controls the expression of the eight viral genes that make up the remainder of the genome. To do this the NCR contains short DNA sequences or motifs that bind both cellular and viral proteins known as transcription factors; this binding can either turn on or turn off gene expression by activating or repressing the promoter of the gene.

Two HPV prophylactic vaccines have been developed, these are Cervarix®, a bivalent HPV16/18 VLP vaccine from GlaxoSmithKline, and Gardasil® a quadrivalent HPV16/18/6/11 VLP vaccine from Sanofi Pasteur MSD. The details of these vaccines and their trials are shown in Table 1. The vaccines are sub unit vaccines consisting of virus-like particles or VLPs – synthetic shells composed of the L1 coat protein. These VLPs are morphologically identical to the virus coat but consist only of 1 protein, contain no DNA and are therefore not infectious. Gardasil® was licensed in many countries including the USA and Europe in 2006 and Cervarix® in late 2007.


Cervical cancer is the second most common female cancer (10% of total) in the world. The rates vary seven fold worldwide with invasive cancer rare in the developed world due to effective screening programmes. Cervical cancer in the UK has a bimodal age distribution with a young peak in the under 35s and then a further peak in the more elderly population. Since the late 1980s there has been an increase in the incidence rates of severe dysplasia (which includes the old term carcinoma in situ) for women in England and Wales under 34. This may represent a change in behaviour and increased exposure to the causative virus HPV.

Clinical scenario 1

A 35 year old woman presents to her GP to discuss her cervical smear results. She has two children and smokes 10 cigarettes a day. She is otherwise well with no symptoms. Her cervical smear is reported as severe dyskaryosis.

a. She asks, does this mean cancer?

b. Is there any advice that she can take immediately?

c. Who will she be referred to and how long will this take?

d. What will happen at the hospital? e. What is the long term outlook?

This issue of Clinical Focus is concerned with statin intolerance, a problem commonly encountered in primary care. Management of elevated cholesterol in individuals with established cardiovascular disease, diabetes or high cardiovascular risk has become a routine component of clinical care in both primary care and hospital settings, and has made a significant contribution to the decline in coronary heart disease over the last twenty years. Fortunately, in the considerable majority of cases, lipid goals can be achieved easily through the use of a statin.

The preceding article discusses the frequency of statin intolerance, its main causes and the mechanisms which may underlie statin induced side-effects. In this section, an approach to the management of the statin intolerant patient will be discussed. (Figure 1)

The use of statins to effectively and safely lower cholesterol has revolutionised the treatment and prevention of atherosclerotic vascular disease. Statin treatment has now become a mainstay of the management of patients with diabetes or any form of vascular disease, and in addition is recommended in UK guidelines for otherwise healthy individuals with a ten year risk of cardiovascular disease of 20% or greater. Statin treatment brings very considerable clinical benfits, and in general is well tolerated. However, as with all drug classes, clinically significant side effects may occur and may lead to cessation of treatment, either by the patient or by the clinician. This article will describe the main statin side effects, including their aetiology (where known) and frequency, and will discuss how the risk of statin side effects can be minimised. In the following article, the management of the statin intolerant patients will be discussed.


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