Table 3.
Human papillomavirus (HPV) status detection using p16INK4A immunohistochemical (IHC) staining in combination with HPV DNA PCR or in situ hybridization (ISH) assay
| Study | Cases | Gold standard | Combined with PCR, % | Combined with ISH, % | Compared with single p16INK4A IHC staining, %† | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Both positive | Both positive | Either positive | ||||||||
| Sens. | Spec. | Sens. | Spec. | Sens. | Spec. | Sens. | Spec. | |||
| Smeets et al.11 | 48 | HPV E6/E7 mRNA | 100 | 100 | – | – | – | – | 100 | 79 a |
| Rotnaglova et al.41 | 109 | HPV E6*I mRNA | 100 | 88 | – | – | – | – | 96 | 94 b |
| Schache et al.38 | 108 | HPV E6 mRNA | 97 | 94 | 88 | 90 | – | – | 94 | 82 c |
| Jordon et al.27 | 232 | HPV E6/E7 mRNA | – | – | 86.1 | 97.3 | 98.7 | 81.1 | 97 | 84 d |
| Gao et al.29 | 150 | HPV E6/E7 mRNA ISH | – | – | 69 | 100 | 95 | 85 | 95 | 90 e |
†Criteria for p16INK4A immunohistochemical (IHC) staining as follows. aStaining intensity (graded 0–3 proportional to staining intensity) and the percentage of the tumor cells positively stained per slide were assessed, positive defined as intensity >1 and percentage >10%. bPositive for p16INK4A expression had to show more than 50% of positive cells and reveal nuclear and/or cytoplasmic staining. cP16INK4A IHC was scored as positive if there was strong and diffuse nuclear and cytoplasmic staining present in >70% of the malignant cells. dSignificant differences in AUC were observed for both intensity score and percentage staining. A p16INK4A intensity score cut‐off point of 2 on a scale of 0–3 was most sensitive, and a percentage staining cut‐off point of 35% on a scale of 0–100% was most specific. An H score cut‐off point of 60 on a scale of 0–300 yielded an average sensitivity of 91.6% and specificity of 90.4%. eClassified in a binary manner as positive when >50% of the cells showed nuclear and cytoplasmic staining. –, no data; Sens., sensitivity; Spec., specificity.