Pre-eclampsia (PE) is a hypertensive related syndrome in pregnant women, one of main reasons of foeto-maternal morbidity and mortality. Although a lot of research has been done, the pathophysiology of this condition is still unknown. Transplacental viral transmissions are known to cause pregnancy complications. Recent work done in the “Pathogenesis Laboratory” based at the University of Otago, found 100% of PE associated placentas had the high risk (HR) human papilloma virus (HPV) present. However, if and how HPV directly contributes to pregnancy complications remains unknown. Some evidences have shown up-regulated expression of the tumour protein 53 (p53) in PE placentas. This project investigated if HPV was associated with increased p53. Seventy-one placentas were selected based on the presence or absence of HPV from the existing OPuS study and were divided into specific cohorts according to the presence of HR or low risk (LR) HPV along with the presence or absence of pregnancy complications. Three independent methods were used to detect HPV and p53 expression in placentas including immunohistochemistry for HPV L1 and p53 protein, in situ DNA hybridization to identify high-risk HPV DNA, and in situ RNA hybridization (RNAScope) to identify HR HPV E6 and E7 gene expression. The one-way ANOVA test corrected for multiple comparisons was used to show significantly increased p53 positive cells in the HPV associated cohorts including PE, HR HPV matched, HR HPV non-complicated (all P < 0.0001) and LR HPV cohorts (P < 0.0004) in comparison with HPV negative cohorts. HPV E6 and E7 expression was detected by RNAscope in all three PE placentas investigated. Increased p53 was correlated with the presence of HR and LR HPV in the placenta. Further investigations are planned to determine if the expression pattern of p53 and HPV are cell type specific and also determine the effect of HPV p53 related pathways.