TABLE 1.

Description of the benefits and drawbacks of different HPV detection techniques.

Detection technique	Benefits	Drawbacks	References
HPV PCR	High sensitivity HPV genotype information FFPE manageable Easy and inexpensive technique	No information about viral transcription High risk of contamination (intrinsic and extrinsic)	(49–60)
E6/E7 mRNA RT-PCR	High sensitivity and specificity Detects active viral infection Gold standard for research	Time-consuming Non-FFPE manageable (fresh or frozen tissue only) RNA fragility	(39–45)
E6/E7 mRNA in situ hybridization	High specificity and good sensitivity In situ detection of a transcriptionally active HPV infection FFPE manageable	RNA degradation over time Expensive technique	(62–65, 69–72)
HPV DNA in situ hybridization	In situ detection of HPV DNA High specificity FFPE manageable	Reduced sensitivity (needs a minimum DNA copy number)	(54, 62–67)
P16 immunochemistry	High sensitivity Inexpensive technique FFPE manageable	Moderate specificity Surrogate marker of HPV infection	(8, 62, 63, 70, 71, 81, 82) (87, 88, 92–95)
Serology for antibodies against E6 protein	Present in more than 90% of patient with OPSCC related to HPV16 Easy to set up	Lack of clinical data and hindsight	(119–124, 126)
HPV circulating tumoral DNA by ddPCR	Correlation with clinical outcome Early detection of recurrences in posttreatment monitoring High sensitivity and specificity Low cost	Need to be validated on larger cohorts	(52, 117, 130, 133)

HPV, human papillomavirus; RT-PCR, reverse-transcriptase polymerase chain reaction; ddPCR, droplet digital PCR; FFPE, formalin-fixed paraffin-embedded tissues.