Oropharyngeal cancers: Significance of HPV16 detection in neck lymph nodes

Background: An increasing proportion of oropharyngeal squamous cell carcinomas (OPSCCs) is associated with human papillomavirus (HPV) type 16 infection. Several authors have suggested that HR-HPV DNA could be used as a marker of metastases in cervical cancers. Although HPV16 DNA has been detected in neck lymph node (LN) metastases of HPV16-positive OPSCC, its significance remains controversial. Does this presence correlate to metastatic involvement or is it just the consequence of LN filter function? Objectives: This study aims to analyse the relationship between HPV16 detection in neck LNs of HPV16-positive OPSCC and their pathological status. Study design: HP16-viral load (VL) was quantified by real-time-polymerase-chain reaction in primary tumours and neck LNs, in 11 patients with HPV16-positive OPSCC and in three patients with HPV16-negative OPSCC. HPV16 in situ hybridisation and p16 immunohistochemistry were performed in all LNs. Results: A total of 45 LN levels were assessed. HPV16 DNA was not identified in HPV16-negative OPSCC LNs. All metastatic LNs from HPV16-positive OPSCC had a high VL and the viral DNA was located within tumoural cells. Among 27 pathologically tumour-free LN (PTFLN) levels 16/27 had no detectable VL, whereas the VL was low or medium (<10⁵copies/million cells) in 8/27 and high (>10⁵copies/million cells) in 3/27 PTFLN. In the latter group, no metastatic cell was identified and the viral DNA was located in immune cells. Conclusion: HPV16 detection in LN is explained by its presence within either metastatic cells or immune cells. HPV16 detection in PTFLN is not necessarily correlated to occult LN metastases.