Will HPV vaccination prevent cervical cancer?

We conducted a critical appraisal of published Phase 2 and 3 efficacy trials in relation to the prevention of cervical cancer in women. Our analysis shows the trials themselves generated significant uncertainties undermining claims of efficacy in these data. There were 12 randomised control trials (RCTs) of Cervarix and Gardasil. The trial populations did not reflect vaccination target groups due to differences in age and restrictive trial inclusion criteria. The use of composite and distant surrogate outcomes makes it impossible to determine effects on clinically significant outcomes. It is still uncertain whether human papillomavirus (HPV) vaccination prevents cervical cancer as trials were not designed to detect this outcome, which takes decades to develop. Although there is evidence that vaccination prevents cervical intraepithelial neoplasia grade 1 (CIN1) this is not a clinically important outcome (no treatment is given). Trials used composite surrogate outcomes which included CIN1. High efficacy against CIN1+ (CIN1, 2, 3 and adenocarcinoma in situ (AIS)) does not necessarily mean high efficacy against CIN3+ (CIN3 and AIS), which occurs much less frequently. There are too few data to clearly conclude that HPV vaccine prevents CIN3+. CIN in general is likely to have been overdiagnosed in the trials because cervical cytology was conducted at intervals of 6-12 months rather than at the normal screening interval of 36 months. This means that the trials may have overestimated the efficacy of the vaccine as some of the lesions would have regressed spontaneously. Many trials diagnosed persistent infection on the basis of frequent testing at short intervals, i.e. less than six months. There is uncertainty as to whether detected infections would clear or persist and lead to cervical changes.

Factors Affecting Access to Healthcare: An Observational Study of Children under 5 Years of Age Presenting to a Rural Gambian Primary Healthcare Centre.

MAIN OBJECTIVE: Prompt access to primary healthcare before onset of severe illness is vital to improve morbidity and mortality rates. The Gambia has high rates of child mortality and research is needed to investigate contributing factors further. This study aimed to identify factors affecting access to primary healthcare for children <5 years (y) in rural Gambia focusing on delayed presentation and severe illness at presentation as indicators in a setting where primary healthcare is delivered free of charge. METHODS: Data were extracted from an electronic medical records system at a rural primary healthcare clinic in The Gambia for children (0-5y) between 2009 and 2012. First clinic attendances with malaria, lower respiratory tract infections (LRTI) and diarrhoeal disease, the main contributors to mortality in this setting, were identified and categorized as delayed/non-delayed and severe/non-severe representing our two main outcome measures. Potential explanatory variables, identified through a comprehensive literature review were obtained from an ongoing demographic surveillance system for this population. Variables associated with either delayed/non-delayed and/or with severe/non-severe presentations identified by univariate analysis (p<0.1) were assessed in multivariate models using logistic regression (p<0.05). RESULTS: Out of 6554 clinic attendances, 571 relevant attendances were identified. Delayed presentation was common (45% of all presentations) and there was a significantly reduced risk associated with being from villages with free regular access to transport (OR 0.502, 95%CI[0.310, 0.814], p = 0.005). Children from villages with free regular transport were also less likely to present with severe illness (OR 0.557, 95%CI[0.325, 0.954], p = 0.033). CONCLUSIONS: Transport availability rather than distance to health clinic is an important barrier to accessing healthcare for children in The Gambia, and public health interventions should aim to reduce this barrier.