000			02475 am a22002173u 4500
042			_adc
100	1	0	_aRees, Claire P _eauthor _9620
700	1	0	_aBrhlikova, Petra _eauthor _9621
700	1	0	_aPollock, Allyson M _eauthor _9622
245	0	0	_aWill HPV vaccination prevent cervical cancer?
260			_bSAGE Publications, _c2020-01-21.
500			_a/pmc/articles/PMC7068772/
500			_a/pubmed/31962050
520			_aWe 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.
540			_a© The Royal Society of Medicine
546			_aen
690			_aReview _9623
655	7		_aText _2local
786	0		_nJ R Soc Med
856	4	1	_uhttp://dx.doi.org/10.1177/0141076819899308 _zConnect to this object online.
999			_c1508 _d1508