Q: What is the new screening test for HPV? What research is being carried out on it, and would it really save the NHS millions of pounds?
HPV must be detected by a molecular technique, not by cytology. There is little correlation between HPV changes reported on a smear and the detection of the high-risk types.
It is likely that cytology detects low-risk HPV types, such as HPV 6 and 11, which are responsible for causing visible genital warts, but not cancer. Molecular HPV testing has been around for more than 10 years but has suffered from problems with the techniques.
The new HPV test is called hybrid capture II, and is another variant on molecular testing for HPV. Hybrid capture depends on RNA probes that recognise DNA sequences of relevant (high-risk) HPV types. When they recognise an appropriate strand of DNA, they attach themselves, creating DNA:RNA hybrids.
These hybrids are attacked and captured by special antibodies to which an enzyme is attached. The enzyme responds to the captured hybrid by emitting a light signal. A machine can then detect how much HPV is present by the strength of the light emitted.
The problem with HPV tests so far is that although they identify a lot of CIN, they also give a lot of false positive results. For example, in a London screening study, half the women who had positive HPV tests had no abnormality on colposcopy. Such false positive results would be extremely costly if translated to the whole screening programme.
However, a negative HPV test virtually rules out the chance of any abnormality being present. Women with a mild or borderline abnormal smear who are HPV negative could then be told not to worry, and resources concentrated on those who test positive.
Another problem with HPV testing is that infection is common in young people, but can be transient, and only a small proportion go on to have persistent infection and develop abnormalities. HPV is more significant in women over 30 who have persistent infection.
Looking even further ahead, HPV testing could become a self-sampling technique, a development that would have far-reaching advantages.
Doctors must be aware of the psychosocial consequences of HPV testing. Testing positive for HPV may have an adverse psychosocial impact, so education will be important.
Dr Anne Szarewski, clinical consultant and honorary senior lecturer, Cancer Research UK Centre for Epidemiology, Mathematics and Statistics
Q: The stated maximum dose of gliclazide is 160mg twice daily. Can it be used at higher doses?
The dose-response curve for sulphonylurea drugs, such as gliclazide, glibenclamide and glimepiride tends to flatten off at higher doses. Therefore, although higher doses of gliclazide can be used, the additional benefit will be minimal.
In my experience it is very unusual to see patients on doses higher than the recommended maximum.
Dr Stephen Bain, professor of medicine (diabetes), University of Wales, Swansea.