Aims: If human papillomavirus (HPV) testing is to be included within cervical screening programmes, the importance of multiple HPV infections in cervical neoplasia needs to be determined. This study investigated the diversity of multiple HPV types in a routine cervical screening population, and assessed associations with cervical neoplasia. Methods: Overall HPV prevalence, type specific prevalence, and extent of multiple infection were assessed in residual material from 3444 liquid based cytology samples, using real time GP5+/GP6+ polymerase chain reaction for screening and linear array assay for genotyping. HPV status was studied in relation to age and concurrent cytological evidence of dyskaryosis. Results: Twenty per cent of samples were HPV positive. HPV type diversity was broad, and multiple HPV infections occurred in half of the HPV positive samples. Younger women were significantly more likely to harbour multiple high risk HPV (HR-HPV) infections. Infections with multiple HR-HPV types were found in 3.4% of samples negative for neoplasia and in 33.3%, 41.8%, and 40.4% of samples with borderline, mild, or high grade dyskaryosis, respectively. Single HR-HPV infections were found in 4.9%, 38.6%, 45.0%, and 51.1% of negative, borderline, mild, or high grade dyskaryosis samples, respectively. Conclusions: Multiple HR-HPV infections were most prevalent in young women. Multiple HR-HPV infections were not more frequent in high grade than in low grade cervical neoplasia, reflecting common sexual transmission of multiple HR-HPV. Prospective cohort studies linking sequential loss or gain of HPV types with cytological analysis are required to assess the impact of multiple HR-HPV infections on neoplastic progression.T he implementation of cytology based cervical screening programmes has reduced the incidence of cervical carcinoma world wide. Consequently, the development of improved cytological preparation methods such as liquid based cytology (LBC) and thin layer slide preparation has been welcomed. The addition of high risk human papillomavirus (HR-HPV) testing may further enhance the accuracy of screening programmes. Accumulating evidence suggests that detection of persistent infection with the same HR-HPV type would highlight individuals at greater risk of disease progression,1 2 yet the extent and importance of multiple HR-HPV infections in the progression of cervical neoplasia and its management remain unknown. To investigate these issues it is necessary to use genotyping methods that can track the persistence of specific HPV types and detect infections with multiple HR-HPV types.''Accumulating evidence suggests that detection of persistent infection with the same high risk human papillomavirus (HR-HPV) type would highlight individuals at greater risk of disease progression, yet the extent and importance of multiple HR-HPV infections in the progression of cervical neoplasia and its management remain unknown'' A recent directive issued by the Scottish Executive has promoted the roll out of cervical LBC for use thr...
This updated analysis provides more certainty with regard to the potential cost-effectiveness of LBC compared with conventional Pap smear testing. However, there is uncertainty regarding the relative effectiveness (and cost-effectiveness) of the two main LBC techniques. Further research in the area of utility assessment may be worthwhile and possibly a full cost-effectiveness study of LBC based on a trial of its introduction in a low-prevalence population, although the results of the modelling analysis provide a robust argument that LBC is a cost-effective alternative to conventional cervical cancer screening. A randomised comparison of the two main techniques may also be useful.
Comparison of certified clinical diagnoses with autopsy findings showed that, while the major cause of death was confirmed in 61 per cent. of cases, many diagnoses--both major and contributory--were wrong; many clinical diagnoses were either disproved or relegated to a less important role, and many autopsy findings had not apparently been anticipated. Accuracy was particularly poor in some clinical categories: notably cerebrovascular disease and infections. In these, the diagnosis was more often wrong than right. Thus, death certificates are unreliable as a source of diagnostic data. The clinician's confidence in his major diagnosis bore a fairly close relationship to the frequency of its confirmation. Nevertheless, even when certified as "fairly certain", the major diagnosis was wrong in about one-quarter of these cases. An attempt was made to assess the significance of incorrect diagnoses; one half of these might be clinically significant. Diagnostic accuracy did not improve with the time spent in hospital, and it bore an inverse relationship to the patient's age.
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