Human papillomavirus prevalence in pregnant women living with human immunodeficiency virus infection: a scoping review of the literature.

OBJECTIVES: Studies already pointed out the increased risk of human papillomavirus (HPV) positivity and the implied risk of cervical dysplasia and even cervical carcinoma in pregnant women with human immunodeficiency virus (HIV) infection. Nevertheless, due to less data there is still no standardised and expanded screening for this high-risk group. CONTENT: Two online databases (PubMed, EMBASE) were used to identify eligible studies. Results are shown in percentages. Wherever useful the arithmetic mean was calculated. SUMMARY: Seven studies were included. Pregnant WLWH showed HPV prevalence between 34 and 98.4 %. Different sensitivity and specificity among PCR methods for HPV detection could be a reason for the large range concerning HPV prevalence. Risk factors like Age, Smoking, Sexuality, HIV status and education level should always be taken into account. Association between HPV prevalence and level of CD4 cells or HIV virus load was seen. In which way use of Antiretroviral Therapy (ART) could decries the risk for HPV infections is still discussed. When cytology was performed only few high-grade squamous intraepithelial lesion (HSIL) were found. OUTLOOK: Standardisation and expansion of preventive screening for cervical dysplasia and carcinoma for pregnant WLWH is necessary. Then better comparability of the data will also be achieved.

Human Papillomavirus E7 and p16INK4a mRNA Multiplexed Quantification by a QuantiGeneTM Proof-of-Concept Assay Sensitively Detects Infection and Cervical Dysplasia Severity.

BACKGROUND: Persistent infection with human papillomavirus (HPV) can lead to cervical cancer (CxCa). During the progression to CxCa, the expression of HPV oncogenes E6 and E7 is upregulated. In turn, cellular proteins such as p16INK4a are also modulated. The combined detection of HPV oncogenes and cellular biomarkers indicative for dysplasia could be informative and convey better specificity than the current HPV tests that cannot discriminate transient infection from dysplastic changes. METHODS: The QuantiGeneTM 2.0 Plex Assay platform was chosen for the effective multiplexing and quantitative detection of seven HPV-E7 mRNA targets (HPV6, 16, 18, 31, 45, 59, and 68) and the cellular mRNA of p16INK4a as a biomarker for HPV-induced transformation. Actin-beta (ACTB) and hypoxanthine-guanine phosphoribosyltransferase 1 (HPRT1) were included as reference markers. Sequences for the specific capture and detector probes were customized and developed by ThermoFisher and formulated as a QuantiGene proof-of-concept (QG-POC) plex-set. The crude lysates of the HPV-positive cervical cancer cell lines CaSki (HPV16), HeLa (HPV18), MRHI-215 (HPV45), Erin59 (HPV59), ME180 (HPV68), and the HPV-negative cell line C33A, as well as liquid-based cytology smear samples (n = 441) were analyzed. The study was a proof-of-concept evaluating the feasibility of the platform. Logistic regression and receiver operating characteristic (ROC) analyses were performed to test for the sensitivity and specificity of HPV detection and dysplastic stage discrimination. RESULTS: A QG-POC assay specifically and sensitively detects the HPV-E7 mRNA of seven different genotypes with an assay linearity between 20 and 13,000 cells. Cellular mRNA was detected from the crude lysates of cell lines and of cellular material from clinical liquid-based cytology smear samples. By combining HPV-E7 and p16INK4a expression normalized to ACTB, high-grade dysplasia (HCIN) and invasive cervical cancer (CxCa) were detectable, discriminable, and correlated to the biomarker expression strength. The ROC analysis from the multivariate logistic regression model including HPV-E7 and p16 INK4a resulted in an AUC of 0.74, at the optimal cut-off (sensitivity: 70.4%; specificity: 66.0%) for HCIN detection. CxCa was detected with an AUC of 0.77 (sensitivity: 81.8%, specificity: 77.4%). CONCLUSIONS: The QG-POC assay is sufficiently sensitive to detect and quantify HPV-E7 and cellular mRNA species. Multiplexing allows the specific detection of at least 10 analytes in a single reaction. Determining the abundance of E7 and p16INK4a transcripts when normalized to ACTB is informative about the presence of cervical dysplasia and potentially discriminates between low-grade and high-grade dysplasia and invasive cervical cancer. Further studies including more HPV genotypes and biomarkers are warranted.

A Technical Comparison of Human Papillomavirus Genotyping Assays from a Population-Based Cervical Cancer Screening in South Central Ethiopia.

Purpose: High-risk Human Papillomavirus (HPV) is the most important cause of cervical cancer. The highest burden of disease is seen in Low- and Low-Middle-Income Countries (LMIC). Several new HPV screening assays have been developed for high-risk HPV (hr-HPV) testing. We compared the performance and adequacy of three HPV genotyping assays on samples from a population of rural women in south-central Ethiopia. Patients and Methods: One hundred and ten cervical swabs from rural women screened for HPV were assayed. HPV DNA was tested using MPG-Luminex Assay, Anyplex II HPV HR Detection, and EUROArray HPV. MPG-Luminex Assay was used as a reference method to compute the sensitivity and specificity of the two commercial assays in detecting hr-HPV infections. Results: Of the 110 samples, MPG-Luminex Assay found 18.2% positive for the 14 hr-HPV and 7.3% for the probable hr-HPV genotypes. Anyplex™ II HPV HR Detection assay and EUROArray HPV Assay identified 21.82% and 12.7% samples, respectively, for the 14 hr-HPVs and both 7.3% for the probable hr-HPV genotypes (κ=0.734). Among the 14 hr-HPV genotypes, the genotype-specific agreement of the three HPV genotyping assays was moderate or better for HPV16, 31, 35, 39, 52, 56, 66 and 68. The aggregated sensitivity in detecting the 14 hr-HPV infections of Anyplex™ II HPV HR Detection and EUROArray HPV assays was high, 100% and 70%, respectively. The specificities of Anyplex™ II HPV HR Detection and EUROArray HPV were 95.6% and 100%, respectively. Conclusion: The three evaluated assays showed similar analytical performance in the detection of hr-HPV infections and moderate or better concordance in HPV genotyping. This study is part of the ongoing cluster-randomized trial that has been registered in clinicaltrials.gov (NCT03281135) on September 13, 2017.

Genotype-specific high-risk human papillomavirus infections and risk factors for cervical dysplasia in women with human immunodeficiency virus in Germany: results from a single-center cross-sectional study.

OBJECTIVE: Women living with HIV have an increased risk of human papillomavirus (HPV) infection and cervical cancer. Little is known about genotype-specific HPV prevalence, the impact of antiretroviral therapy, immunological status, and additional risk factors in women living with HIV in Germany. The goal of this study was to characterize the risk profile for cervical dysplasia in these women. METHODS: Patients with HIV infection presenting at Charité-Universitätsmedizin Berlin from October 2017 to September 2020 were included and underwent gynecological examination, colposcopy, cervical cytology and HPV genotype testing. HPV genotypes were stratified by carcinogenicity. Atypical squamous cells of undetermined significance or higher were considered abnormal cytology. Data were analyzed by SPSS software (version 26, 2019). A two-tailed p-value ≤0.05 was considered statistically significant. RESULTS: A total of 84 women were evaluated. The majority (95.2%) received antiretroviral therapy. Median CD4 cell count was 564 cells/µl (range 20-1969). 95.2% were previously screened for cervical cancer. High-risk HPV prevalence was 44%. High-high-risk HPV subtypes (16, 18, 31, 33, 45, 52, 58) were significantly associated with abnormal cytology (p<0.001). HPV16 was the most common genotype (23%), was significantly associated with abnormal cytology (p=0.002) and was the main risk factor for abnormal cytology (OR 8.55, 95% CI 2.15 to 34.13, p=0.002), followed by age <35 years (OR 4.96, 95% CI 1.23 to 19.61, p=0.033) and cigarette smoking (OR 3.944, 95% CI 0.98 to 15.88, p=0.053). CONCLUSIONS: Antiretroviral therapy and adherence to cervical cancer screening was high. High-high-risk HPV, especially HPV16, coincided with high incidence of cytological abnormalities. Women living with HIV in Germany have adequate immune status and are often pre-screened for cervical cancer, and therefore have a different risk profile for cervical dysplasia than in low-income or medium-income countries. Adapted screening programs should be defined.

Population-based human papillomavirus infection and genotype distribution among women in rural areas of South Central Ethiopia.

In Ethiopia, cervical cancer is the second leading cause of morbidity and mortality from all cancers in women. Persistent infection with human papillomaviruses (HPV) plays a key role in the development of cervical intraepithelial neoplasia and invasive cervical cancer. To establish baseline data on the population-based prevalence of HPV infection and genotype distribution, we investigated cervical HPV epidemiology among rural women. This population-based study was conducted among rural women aged 30-49 years in Butajira, south-central Ethiopia. A total of 893 samples were tested from 1020 screened women. A self-sampling device (Evalyn Brush, Rovers, Oss, The Netherlands) was used and HPV presence and genotype was determined using multiplexed genotyping (MPG) by BSGP5+/6+ PCR with Luminex read out. The HPV positivity rate was 23.2% (95% CI: 23.54-22.86%) and 20.5% (95% CI = 20.79-20.21) and 10.3% (95% CI = 10.52-10.08) women were high-risk (hr- and low-risk (lr-) HPV positive, respectively. Fifty five (7.2%) of the women showed multiple hr-HPV infections. Age-specific hr-HPV infection peaked in the age-group 30- to 34 years old (58.6%) and decreased in 35-39, 40-44 and 45-49 years to 20.4%, 4.5% and 3.8% respectively. The top five prevalent hr-HPV genotypes were HPV16 (57.1%), 35 (20.3%), 52 (15.8%), 31 (14.1%), and 45 (9.6%) in the Butajira district. As a first population-based study in the country, our results can serve as valuable reference to guide nationwide cervical cancer screening and HPV vaccination programs in Ethiopia.