(O1) HPV genotypes identified in migrant women living with HIV are not covered for by current HPV vaccines; results from an interim analysis

Författare/Medförfattare

Christina CARLANDER (1,2), Camilla LAGHEDEN (3), Carina EKLUND (3), Sara NORDQVIST KLEPPE (3), Philippe WAGNER (2), Aylin YILMAZ (4), Kristina ELFGREN (5), Anders SÖNNERBORG (1), Pär SPARÉN (7), Joakim DILLNER (3)

Affiliates

1) Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden. 2) Centre for Clinical Research Västmanland, Västmanland County Hospital, Uppsala University, Västerås, Sweden. 3) Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. 4) Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 5) CLINTEC, Department of Obstetrics and Gynaecology, Karolinska University Hospital Huddinge, Stockholm, Sweden. 7) Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Abstrakt

Background
Distribution of Human papilloma virus (HPV) genotypes causing high-grade cervical neoplasia varies in different geographic regions and it has been suggested that migrant women carry the HPV types present in their original countries. While women living with HIV (WLWH) have been found to carry other high risk (HR) HPV genotypes than HIV negative women (HNW) there is little data regarding migrant women living with HIV in Europe. We conducted a country of birth matched population-based register study with the aim of assessing whether HPV-genotypes detected in women diagnosed with high-grade cervical neoplasia in Sweden differ depending on HIV status. This would have implications for HPV-screening algorithms and for the choice of HPV vaccine in this population.
Methods
The Swedish National InfCareHIV Registry was linked with the Swedish National Cervical Screening Registry. We identified all WLWH, living in the Counties of Stockholm and Gothenburg sometime between 1983 and 2014, with a diagnosis of cervical intraepithelial neoplasia grade 2, grade 3 or adenocarcinoma in situ or cervical cancer (CIN2+) (n=179). For each WLWH we randomly selected two HIV-negative women, living in the same counties sometime between 1983 and 2014, diagnosed with CIN2+, matched for country of birth (n=321). We retrieved cervical tissue blocks of included women from regional biobanks and performed HPV genotyping using modified general primer PCR with Luminex genotyping and real-time PCR targeting E7/E6 regions of HPV 16/18. Type-specific HR HPV prevalence was compared using prevalence ratios (PR) calculated with Poisson regression analysis. All models were adjusted for age, grade of cervical lesion and region of birth.
Results
In this interim analysis 54 WLWH and 123 HNW had valid HPV genotype results of which 50 (93%) WLWH and 111 (90%) HNW were HPV-positive. Although the most common single infection was HPV 16 for both WLWH (16%) and HNW (44%), WLWH were significantly less likely to be infected with HPV 16 (Prevalence ratio (PR)= 0.4, 95% CI: 0.2-0.8). WLWH were twice as likely to be infected with multiple HR HPV than HNW (44 vs. 22 %; PR= 2.0, 95% CI: 1.3-3.2). Only 20% of WLWH vs. 49% of HNW had HR HPV types detected that would have been covered for by the bivalent and quadrivalent HPV vaccines (HPV 16 and/or 18) (PR= 0.5, 95% CI: 0.3-08). Even HR HPV types covered for by the nine-valent HPV vaccine (16/18/31/33/45/52/58) were significantly less detected in WLWH (50%) compared to HNW (80%) (PR=0.7, 95% CI 0.5-0.9).
Conclusion: To our knowledge this is the first study where HPV genotype infection in migrant women, originating from the same countries of birth and diagnosed with CIN2+, have been compared depending on HIV status. WLWH had significantly less proportion of HPV genotypes detected that would have been covered for by current HPV vaccines. This study confirms that HPV-genotype distribution in high-grade cervical lesions is more dependent on HIV status than on region of birth and this must be accounted for when choosing HPV-screening algorithms and HPV vaccine implementation in the HIV-infected population.