Some investigators have proposed that: (i) different HPV genotyping kits cannot fully identify all subtypes of HPV; (ii) the diagnostic efficacy of IHC staining p16 across countries was variable; (iii) p16 overexpression may be related to an Rb dysfunction, but Rb dysfunction may not be related to HPV infection; (iv) tumor heterogeneity or sampling bias [45,46] might cause a discrepancy between tissue p16 levels and HPV genotyping results [44]. The gene discussed is RB1; the disease is neoplasm.