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PD-L1 expression in squamous cervical carcinomas of Mozambican women living with or without HIV
Örebro universitet, Institutionen för medicinska vetenskaper. Pathology Department, Maputo Central Hospital, Maputo, Mozambique; Faculty of Medicine, Eduardo Mondlane University, Maputo, Mozambique.ORCID-id: 0000-0002-0218-6190
Medical Oncology Service, Maputo Central Hospital, Maputo, Mozambique.
Pathology Department, Maputo Central Hospital, Maputo, Mozambique; Faculty of Medicine, Eduardo Mondlane University, Maputo, Mozambique.
Örebro universitet, Institutionen för hälsovetenskaper.ORCID-id: 0000-0002-4669-1367
2024 (Engelska)Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 14, nr 1, artikel-id 12974Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Programmed death-ligand 1 (PD-L1) is overexpressed in squamous cervical cancer (SCC) and can be used for targeted immunotherapy. The highest mortality rates of SCC are reported in sub-Saharan Africa, where Human immunodeficiency virus (HIV) prevalence is high. In Mozambique most SCC patients present at advanced stages. Thus, there is a need to introduce new treatment options. However, immunocompromised patients were frequently excluded in previous clinical trials. Our aim was to determine if PD-L1 expression in SCC is as prevalent among women living with HIV (WLWH) as among other patients. 575 SCC from Maputo Central Hospital were included. HIV status was available in 266 (46%) cases PD-L1 expression was scored through tumour proportion score (TPS) and combined positive score (CPS). PD-L1 was positive in 20.1% of the cases (n = 110), TPS (score ≥ 25%) and in 26.3% (n = 144), CPS (score ≥ 1). Stratifying according to the HIV status, WLWH were TPS positive in 16.7%, compared to 20.9%, p = 0.43, and concerning CPS 21.1% versus 28.7%, p = 0.19, respectively. PD-L1 status was not influenced by stage, Ki-67 or p16, CD8 expression influenced only CPS status. Our data indicates that the documented effect of PD-L1 therapy on SCC should be confirmed in randomized clinical trials in an HIV endemic milieu.

Ort, förlag, år, upplaga, sidor
Nature Publishing Group, 2024. Vol. 14, nr 1, artikel-id 12974
Nationell ämneskategori
Cancer och onkologi
Identifikatorer
URN: urn:nbn:se:oru:diva-114103DOI: 10.1038/s41598-024-63595-7ISI: 001244399200099PubMedID: 38839923Scopus ID: 2-s2.0-85195341528OAI: oai:DiVA.org:oru-114103DiVA, id: diva2:1866375
Forskningsfinansiär
Sida - Styrelsen för internationellt utvecklingssamarbeteTillgänglig från: 2024-06-07 Skapad: 2024-06-07 Senast uppdaterad: 2024-10-25Bibliografiskt granskad
Ingår i avhandling
1. Human papillomavirus in cervical carcinoma in an HIV endemic milieu, Moçambique
Öppna denna publikation i ny flik eller fönster >>Human papillomavirus in cervical carcinoma in an HIV endemic milieu, Moçambique
2024 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Cervical cancer (CC) is the fourth most frequent cancer and cause of death related to cancer in women worldwide. CC is mainly caused by a persistent infection with human papillomaviruses (HPV). Mozambique is one of the African countries with high prevalence of HPV and HIV. The development of CC may be different in HIV immuno-compromised patients. In this thesis we investigated both the pathogenetic perspective of HPV, and the expression of immunotherapeutic target concerning the possible impacts in an HIV endemic milieu. In paper I, virtual tissue microarrays (TMA) were used to validate the representativity to study biomarkers in CC compared to whole slide images. Our study presents an approach to address TMA sampling that could be generalized to TMA-based research. In paper II, the immunoregulatory programmed deathligand 1 (PD-L1) was immunohistochemically assessed in cervical squamous carcinomas (SCC) in TMA. 575 cases of SCC were included, HIV status was available in 46% cases. Our findings indicated that the immunotherapeutic target of PD-L1 is not influenced by HIV status. In paper III, 40 cases of endocervical adenocarcinomas (ECA) were included. HIV status was established, and HPV was detected in all cases. In paper IV, 260 cases of SCC with known HIV status, were assessed concerning HPV genotype differences between HIV positive and negative cases. With a combination of HPV detection methods, almost all cases of our series were HPV positive. Our results in paper III and IV indicate that the newly established vaccination scheme in Mozambique, using quadrivalent vaccine would have the same potential to prevent morbidity and reduce mortality of CC regardless of a concomitant HIV infection or not.

Ort, förlag, år, upplaga, sidor
Örebro: Örebro University, 2024. s. 79
Serie
Örebro Studies in Medicine, ISSN 1652-4063 ; 300
Nyckelord
Cervical cancer, HPV, HIV, Tissue microarray, vaccine, PD-L1
Nationell ämneskategori
Annan medicinsk grundvetenskap
Identifikatorer
urn:nbn:se:oru:diva-116081 (URN)9789175295862 (ISBN)9789175295879 (ISBN)
Disputation
2024-11-19, Örebro universitet, Campus USÖ, hörsal X1, Södra Grev Rosengatan 32, Örebro, 09:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2024-09-17 Skapad: 2024-09-17 Senast uppdaterad: 2024-11-22Bibliografiskt granskad

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