ASSOCIAÇÃO ENTRE A COINFECÇÃO COM MÚLTIPLOS TIPOS DE PAPILOMAVIRUS HUMANO (HPV) E O PROGNÓSTICO DO CÂNCER DO COLO DO ÚTERO

Abstract

Introduction/Objective: Cervical cancer (CC) is one of the most prevalent malignant neoplasms among women worldwide. In Brazil, CC is the third most common type of cancer among women, behind breast cancer and colorectal cancer. The main risk factor for cervical cancer is persistent infection with high-oncogenic risk Human Papillomavirus (HPV). More than 200 HPV genotypes have been described, and single infections, as well as co-infections with multiple genotypes, are described in precursor lesions and cervical cancer. However, studies on the clinical significance and prognosis of co- infections with multiple genotypes present divergent results. Therefore, this study aims to evaluate the clinical significance of the association between coinfection with multiple HPV genotypes and the prognosis of cervical cancer. Methodology: This is a systematic literature review, which used the PubMed and Medline databases. The descriptors used in the search included “multiple HPV infections AND prognosis; multiple HPV infections AND lesion severity”. The abstracts of the articles were read in order to find those that best responded to the objectives proposed by this review. The review was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta Analyses) and the protocol was submitted for registration in PROSPERO (International Prospective Register of Systematic Reviews), under number CRD42024582763. The search date was 08/17/2024, and primary and descriptive studies that investigated the clinical significance of co-infections by multiple HPV types and their impact on the prognosis of cervical cancer were included. Results: Of the 152 studies identified, 21 met the inclusion criteria. All investigated invasive CCU, with 12 also investigating CIN2 and CIN3. These studies were developed in hospitals, universities and research institutes in several countries. In total, 60,089 women were analyzed, of which 5,504 presented invasive CC, with 5,100 HPV-positive cases. Thus, 18 studies differentiated the histological types of squamous cell carcinomas (SCC) and adenocarcinomas (AD), 11 evaluated FIGO staging and eight evaluated survivals. The studies used PCR to amplify HPV viral DNA, complemented by different genotyping methods to identify viral GEtypes. The tests applied detected between 14 and 38 types of HPV, including high and low oncogenic risk variants. The overall prevalence of multiple co-infections in the studies was 20%, ranging from 0% to 81%. Three studies demonstrated a significant association between multiple coinfections and survival, evidenced by a significant reduction in overall survival, cancer-specific survival, and progression-free survival. Furthermore, significant associations were found between multiple infections and increased tumor size, lymph node involvement, and higher rate of recurrence and distant metastases, resulting in a worse prognosis. These findings discussed the clinical importance of multiple HPV coinfections as a prognostic factor, highlighting the relevance of this variable to guide treatment and monitoring strategies in patients with CC. Conclusion: This review showed that multiple HPV coinfections can be associated with worse clinical outcomes in CC, such as shorter survival and greater resistance to treatment. Although not decisive, our results highlight the importance of evaluating the profile of co-infections by multiple types of HPV in the risk stratification of cervical cancer.