Table 2 Summary table of key outcomes from each study.

From: Value of p53 sequencing in the prognostication of head and neck cancer: a systematic review and meta-analysis

Study

Anatomical subsite of HNSCC

Total sample size

Sample preservation method

Clinical outcome measures (survival)

Summary of key outcomes

Kobayashi et al.32

Mixed

284

Formalin-fixed paraffin-embedded

Overall

Disease/progression-free

– Significantly worse OS, LFFS and DMFS with adverse p53 functional status

– Significantly higher local recurrence with adverse p53 with resection margins > 6 mm

Scheel et al.22

Larynx

58

Formalin-fixed paraffin-embedded

Overall

Disease-specific

– No significant difference in response to chemotherapy according to TP53 mutation status

– Significantly worse DSS in TP53 high-risk mutation group

- No significant difference in time to indication for surgery according to TP53 status

Lapke et al.33

Oral

333

Formalin-fixed paraffin-embedded

Overall

Disease/progression-free

Disease-specific

– Significantly worse OS and DSS with TP53 mutant vs WT

– No difference in DFS between groups

– TP53 DBD missense mutations significantly associated with worse OS, DSS and DFS

Dubot et al.34

Mixed

122

Snap frozen in liquid nitrogen

Overall

– Significantly worse OS in TP53 mutant vs WT

Caponio et al.35

Mixed

415

Various—bioinformatics study on pre-existing datasets

Overall

Disease/progression-free

– Significantly worse OS in TP53 mut vs WT (irrespective of mutation)

– Significantly worse OS with mutations in B-strand/bridge of p53 secondary structure

– Homozygous mutations in TP53 significantly associated with poorer OS and DFS than heterozygous

– Transition in p53 interactome in HNSCC with TP53 mutations

Mundi et al.36

Oral

123

Immediate DNA extraction following surgical resection; storage on ice for transport

Overall

Disease/progression-free

– Significantly worse OS in TP53 mutant group

Cho et al.37

Nasopharynx

22

Formalin-fixed paraffin-embedded

Overall

– Mutations in TP53 significantly enriched in patients with disease relapse. Significantly worse OS in TP53 mutant group

Bosch et al.23

Mixed

361

Snap frozen in pre-cooled isopentane/liquid nitrogen immediately after resection

Overall

– OS was not significantly different between TP53 mutation classes, irrespective of TNM stage, TP53 mutation type and tumour location

Sisk et al.38

Mixed

32

Snap frozen in liquid nitrogen

Overall

– Significantly worse OS in TP53 mutant group, and possible interaction between TP53 and HPV status

Fallai et al.24

Oropharynx

68

Formalin-fixed paraffin-embedded

Overall

Disease/progression-free

Disease-specific

– No difference in survival between TP53 mutant vs WT group

– No difference in OS, DFS and DSS between 'disruptive' TP53 mutation vs WT

Bradford et al.25

Larynx

26

Formalin-fixed paraffin-embedded

Overall

– No significant difference between TP53 mutant group vs WT group in OS and response to chemotherapy

– A significant association between TP53 mutations and advanced tumour stage was identified

Mineta et al.39

Mixed

58

Formalin-fixed paraffin-embedded

Overall

Disease-specific

– TP53 mutation significantly associated with worse OS

Kozomara et al.40

Oral

42

Fresh tumour sections (n = 38) and paraffin-embedded tissues (n = 12)

Overall

– TP53 mutation significantly associated with worse OS

Miyahara et al.41

Larynx

28

Fresh frozen (method not specified)

Overall

– TP53 mutation not significantly associated with worse OS

– Worse survival identified in patients with p53 protein over-expression

Chomchai et al.42

Larynx

45

Snap frozen in liquid nitrogen

Overall

Disease/progression-free

– OS was significantly better in patients with a TP53 mutation compared to WT

– Trend towards improved DFS with TP53 mutation

– No difference in progression-free survival between groups

Lindenbergh-van der Plas et al.26

Mixed

141

Snap frozen in liquid nitrogen

Overall

Disease/progression-free

– No significant difference in PFS in TP53 mutants (overall) vs WT

– Significantly worse PFS on multivariate analysis with truncating mutations in TP53 compared to WT

– Disruptive mutations, hotspot mutations and mutations in DNA-binding domains appeared to have no significant influence on OS or PFS

Bandoh et al.27

Sinonasal

57

Formalin-fixed paraffin-embedded

Overall

Disease/progression-free

– No significant difference in OS and DFS between TP53 mutant and WT groups on multivariate analysis

Yamazaki et al.28

Oral

118

Snap frozen in liquid nitrogen

Overall

– No significant difference in OS between WT and mutant TP53 groups

– Significantly worse OS in patients with TP53 mutations in conserved regions and DNA-binding domains vs other mutation sites

Alsner et al.29

Mixed

114

Formalin-fixed paraffin-embedded

Overall

Disease/progression-free

Disease-specific

– Significantly worse loco-regional control in patients undergoing radiotherapy with TP53 mutations compared to WT, but not surgery

– Significantly worse OS and DFS in patients with mutant p53 vs WT

Russo et al.30

Larynx

81

Fresh frozen (method not specified)

Overall

Disease/progression-free

– TP53 mutation significantly associated with both poorer OS and DFS

– Exon 5 TP53 mutations significantly associated with poorer OS and DFS, and exon 8 mutations associated with OS

Poeta et al.31

Mixed

420

Snap frozen at – 80 °C and paraffin-embedded specimens

Overall

Disease/progression-free

– TP53 mutation significantly associated with worse OS

– Disruptive TP53 mutations demonstrated significantly worse OS than WT, but non-disruptive TP53 mutations did not

– Significantly reduced DFS in TP53 mutant group compared with WT, irrespective of mutation type

Hong et al.43

Oral

202

Formalin-fixed paraffin-embedded

Overall

Disease/progression-free

– TP53 mutation status not significantly associated with loco-regional control, DFS and OS on multivariate analysis

Vossen et al.44

Oral

77

Fresh frozen (method not specified)

Disease/progression-free

– No significant difference in PFS according to TP53 mutation status

Resteghini et al.45

Oral

67

Formalin-fixed paraffin-embedded (FFPE)

Disease/progression-free

– No significant difference in DFS according to TP53 functional status, though trend towards improved prognosis with TP53 functioning patients

Kozomara et al.46

Oral

32

Fresh frozen (method not specified)

Disease/progression-free

– Significantly worse DFS in patients who were TP53 mutation-positive compared to WT