Infection status and survival impact of high-risk human papillomavirus in cervical adenocarcinomas: A systematic review and meta-analysis

Abstract

Objective

Cervical adenocarcinoma (CAC) comprises a heterogeneous group of tumors that are not universally associated with HPV infection. As has been shown in other organs, it is becoming increasingly apparent that HPV status significantly affects the prognosis of adenocarcinoma. We conducted a systematic review and meta-analysis to investigate the infection status of high-risk Human papillomavirus (hrHPV) in CAC and evaluate its impact on the survival of patients.

Methods

PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials.gov were searched from inception to May 1st, 2022. Data on HPV infection status and survival outcomes were evaluated using STATA 16.0.

Results

Seventy-one studies with 11,278 participants were included in HPV infection analysis and eight studies with 1099 participants were included in prognosis analysis. The HPV infection rate (including high-risk and low-risk) and hrHPV infection rate in CAC were 75% (95% CI 0.70–0.80, 6978 participants) and 75% (95% CI 0.70–0.81, 4906 participants), respectively. HPV-16 and -18 were the most common HPVs in CAC, with pooled infection rates of 37% (95% CI 0.33–0.41, 7848 participants) and 34% (95% CI 0.30–0.38, 7730 participants), respectively. hrHPV infection was associated with better overall survival (HR 0.23, 95% CI 0.11–0.47, 1013 participants), better disease-free survival (HR 0.18, 95% CI 0.07–0.43, 292 participants), better progression-free survival (HR 0.20, 95% CI 0.08–0.47, 271 participants) and less recurrence (RR 0.30, 95% CI 0.07–0.43, 181 participants).

Conclusion

HPV infection rates were high in CAC. HPV-16 and -18 had the highest infection rates in CAC. However, hrHPV infection was associated with better survival and less recurrence. Future studies should clarify the relationship between hrHPV infection and other prognostic factors and make reasonable treatment strategies for CAC with different HPV status. Protocol registration: CRD42022319390.