Usefulness, methods and rationale of lymph nodes HPV-DNA investigation in estimating risk of early stage cervical cancer recurrence: a systematic literature review.

Metastatic involvement of pelvic lymph-nodes (LNs), generally found in 0-29.3 % of early stages, is the most important prognostic factor in cervical cancer (CC). However, even in non-metastatic LNs, recurrence rate reaches 10-15 %. The role of HPV-DNA presence in pelvic LNs has been a point of debate in the last two decades. The aim of this systematic review is to collect all available data about LNs HPV-DNA detection in patients affected by early-stage CC in order to elucidate its clinical and surgical usefulness to choose the best surgical treatment, the necessity of adjuvant therapy and to estimate the overall oncological prognosis. The available data in this field results very patchy and often conflicting in the results. The high correlation between HPV-DNA genome detected in primary lesion and the one detected in LNs, as well as the high correlation between LNs metastatic involvement and HPV-DNA presence, lead to hypothesize that LNs HPV presence represents a potential risk-factor for recurrence and poor oncological prognosis. The large disparities in recurrence-rate of cases with LNs positive for HPV-DNA test and negative for metastases could be explained by the relative "inappropriateness" of PCR test to discriminate the presence of HPV-genome alone (condition necessary but not sufficient) or in association with squamous cells (condition necessary and sufficient). The use of ISH test for HPV-DNA detection in LNs, particularly if associated to CK19-assay, improve the accuracy of micro-metastasis detection, and the identification of patients with negative histology but potentially at high-risk of recurrence and poor oncological prognosis.