Review question
The review is going to resolve conflicting evidence: whether the P16 CpG island methylation is important for carcinogenesis of hepatocellular carcinoma.

Sources to be searched
Medline; PubMed; Embase; Cochrane Library; Biological Abstracts; BA; Science Citation Index (SCI). Chinese data: cnki; CBM; 《医学中央雑誌》. NRR; CCT; CDC; DH; HC; FDA.

Types of study to be included
Parallel-group or cross-over design, irrespective of blinding, publication status, or language. For cross-over trials, only data from the first phase of the trial will be used. Quasi-randomised trials will be excluded.

Participants
Patients with hepatocellular carcinoma will be included. The presence of hepatocellular carcinoma should have been defined by histology, or cytology, or by clinical diagnosis(typical images indicating colorectal cancer on ultrasound (US), computed tomography (CT), or angiography), i.e. Patients at risk of hepatocellular carcinoma but without actual cancer will not be considered.

Interventions
P16 CpG island methylation versus no intervention.

Primary outcomes
1. Whether P16 CpG island methylation exists in hepatocellular carcinoma
2. P16 CpG island methylation may be a prognos ticfactor of hepatocellular carcinoma.

Key secondary outcome
1. P16 CpG island methylation may play an important role in hepatocarcinogenesis

Strategy for data synthesis
Meta-analysis