Figure 1.
Minimal criteria to prove a causal role of HPV infections in carcinogenesis are schematically outlined by this diagnostic algorithm. Upon detection of HPV‐DNA fragments (at least one genome equivalent per cell, criterion a), samples should be stained for p16INK4a using immunohistochemistry (criterion c). For practical reasons p16‐immunohistochemisty (p16‐IHC) may be used as “search test” for HPV‐associated cancers and followed by HPV‐DNA detection.14 For samples of the oropharyngeal or anogenital tract, the causal role of oncogenic HPV types is sufficiently documented to assume that if they are positive for HPV‐DNA and p16 IHC, that the oncogenic HPV infection is most likely the causative agent. For all other cancer samples for which the causal role of oncogenic HPV infections has not yet been established, further proof by detecting the expression of the viral oncogenes using the E6*‐PCR (criterion b) is highly recommended as described in the text.