Seth‐Frerich Fobian

Increased human papillomavirus viral load is correlated to higher severity of cervical disease and poorer clinical outcome: A systematic review

Abstract Cervical cancer is the fourth most common cancer in women worldwide and is caused by persistent infection with high‐risk types of human papillomavirus (HPV). HPV viral load, the amount of HPV DNA in a sample, has been suggested to correlate with cervical disease severity, and with clinical outcome of cervical cancer. In this systematic review, we searched three databases (EMBASE, PubMed, Web of Science) to examine the current evidence on the association between HPV viral load in cervical samples and disease severity, as well as clinical outcome. After exclusion of articles not on HPV, cervical cancer, or containing clinical outcomes, 85 original studies involving 173 746 women were included. The vast majority (73/85 = 85.9%) reported that a higher viral load was correlated with higher disease severity or worse clinical outcome. Several studies reported either no correlation (3/85 = 3.5%), or the opposite correlation (9/85 = 10.6%); possible reasons being different categorization of HPV viral load levels, or the use of specific sampling methods. Despite variations in study design and populations, the above findings suggest that HPV viral load is correlated to clinical outcome, and may become an important biomarker for treatment selection and response monitoring for cervical cancer.

High human papillomavirus viral load and local immune dysregulation are associated with poor clinical outcomes in patients with cervical cancer.

Human papillomavirus (HPV) infection is the primary cause of cervical cancer. Higher viral load, that is, a greater abundance of HPV DNA in a tumor, has been associated with poorer clinical outcomes, and may play a role in the more accurate prediction of (non-) responders to treatment. In this study, we investigated the correlation between HPV viral load, clinical outcomes, and immune parameters related to HPV infection. HPV viral load was quantified using quantitative polymerase chain reaction on biopsies from a prospective cohort of women diagnosed with cervical cancer. Patients were categorized into 2 HPV viral load groups based on the optimal fit of a non-linear piecewise regression model. Immunohistochemical staining was used to measure tumor cell characteristics (Ki67, p16 In the 44 women included in our study, high HPV viral load was significantly associated with shorter overall and recurrence-free survival (p = .045 and p = .046, respectively; 2-sided) and positively correlated with an increased risk of lymph node and distant metastasis. In addition, a high HPV viral load was linked to lower percentages of tumor-infiltrating lymphocytes and reduced expression levels of PD-1 and PD-L1. The viral load of HPV in cervical cancer correlates positively to metastasis and recurrence and negatively to survival rates, potentially because of local immune suppression. These results might indicate a lower response to immune checkpoint inhibition in the high viral load group and that other treatment options should still be explored.