HPV Positivity Research Articles

Monitoring HPV Prevalence and Risk Cofactors for Abnormal Cytology in the Post-Vaccination Period among Croatian Women.

The incidence and mortality rate of cervical cancer in Croatia remains a health challenge despite screening efforts. Besides the persistent infection with HPV, the development of cancer is also associated with some cofactors. The goal of this study was to assess circulating HPV genotypes and risk factors for the development of cervical precancer after almost 16 years from the onset of HPV vaccination in Croatia. In this study, a total of 321 women attending gynecological care were evaluated. Relevant medical and demographic information, including cytology, were collected. HPV genotyping was performed by PCR. Comparing the HPV types found in circulation in the pre-vaccination (1999-2015) and post-vaccination periods (2020-2023), a statistically significant reduction in HPV 31 was noted, while the overall prevalence increased in the post-vaccination period. Besides the expected HPV positivity as a risk factor, the history of smoking was associated with LSIL or worse cytology at enrollment. For the first time, this population study revealed a statistically significant shift in the HPV genotype in the post-vaccination period, as well as the confirmation of risk factors for the development of abnormal cytology among Croatian women.

Altered oral microbiome, but normal human papilloma virus prevalence in cartilage-hair hypoplasia patients

BackgroundCartilage-hair hypoplasia (CHH) is a rare syndromic immunodeficiency with metaphyseal chondrodysplasia and increased risk of malignancy. In this cross-sectional observational study, we examined HPV status and oral microbiome in individuals with CHH. Oral brush samples were collected from 20 individuals with CHH (aged 5–59 years) and 41 controls (1–69 years). Alpha HPVs (43 types) were tested by nested PCR followed by bead-based probe hybridization. Separately, beta-, gamma-, mu- and nu- HPV types were investigated, and a genome-based bacterial microbiome sequencing was performed.ResultsWe found a similar alpha HPV prevalence in individuals with CHH (45%) and controls (36%). The HPV types of individuals with CHH were HPV-16 (25%), 27, 28, and 78, and of controls HPV-3, 16 (21%), 27, and 61. Beta HPV positivity and combined beta/gamma/mu/nu prevalence was detected in 11% and 11% of individuals with CHH and in 5% and 3% of the controls, respectively. Individuals with CHH differed from the controls in bacterial microbiota diversity, richness, and in microbial composition. Individuals with CHH had lower abundance of species Mitsuokella sp000469545, Parascardovia denticolens, Propionibacterium acidifaciens, UMGS1907 sp004151455, Salinicola halophilus, Haemophilus_A paraphrohaemolyticus, Fusobacterium massiliense, and Veillonella parvula, and higher abundance of Slackia exigua.ConclusionsIndividuals with CHH exhibit similar prevalence of HPV DNA but different bacterial microbiota on their oral mucosa compared to healthy controls. This may partly explain the previously observed high prevalence of oral diseases in CHH, and regular oral examination is warranted.

IGSF3 tissue expression in squamous cell carcinoma of the oropharynx: a novel tool for prognosis assessment in HPV-related and HPV-unrelated disease.

Biomarkers are not broadly used in the management of head and neck cancers (HNCs). Biomarkers have been beneficial in the management of other cancers, however, not in HNCs. Therefore, we observed the immunopositivity of a novel biomarker called immunoglobulin superfamily member 3 (IGSF3) in tumor tissues in HPV-related and HPV-unrelated OPSCC. Two patient cohorts (C1 and C2) from separate time periods were available for this study (total N = 282). Both consisted of OPSCC patients treated at the Helsinki University Hospital (HUS, Helsinki, Finland) during 2000-2016. For HPV determination, HPV mRNA in situ hybridization was used. Immunohistochemistry was used to assess IGSF3 immunopositivity in cancer tissues. Overall survival (OS) was used as endpoint in the statistical analysis. In C1, stronger immunopositivity of IGSF3 in tumor-infiltrating lymphocytes (TILs) correlated with favorable OS (p = 0.005). Stronger IGSF3 immunopositivity in tumor cells (TCs) was associated with HPV negativity (p = 0.017). Stronger IGSF3 immunopositivity in TILs correlated with HPV positivity (p < 0.001). Elevated IGSF3 immunopositivity in TILs associates with HPV-related tumors and may signify favorable prognosis. The immunopositivity of IGSF3 differs between HPV-related and HPV-unrelated OPSCC.

Risk factors for head and neck squamous cell carcinoma in disease pathogenesis and prognosis: the importance of smoking cessation and the concept of harm reduction

Introduction. Cigarette smoking along with alcohol consumption, infection with human papilloma (HPV) and the Epstein–Barr viruses, is one of the main risk factors for head and neck squamous cell carcinoma. It can also contribute to virus-associated carcinogenesis and affect the clinical and prognostic features of the tumor. Continued smoking at diagnosis of head and neck squamous cell carcinoma is a negative prognostic factor and contributes to reduced patient survival rates. Aim. To analyze the smoking status and the effect of etiopathogenesis on molecular and clinical features in patients with oropharyngeal squamous cell carcinoma (OpSCC). Materials and methods. In patients with OPSCC, the smoking status and the level of motivation to its cessation were clarified. Immunohistochemical analysis of tumor sections from paraffin blocks from the ThermoScentific immunohis-tosteiner was performed using monoclonal antibodies to estrogen receptors α (ERα), programmed death-ligand 1 (pD-L1), Bcl-2, p53 and p16. The percentage of tumor-infiltrating lymphocytes (TILs) in the stromal component of the tumor (hematoxylin and eosin staining) was also analyzed. Results. Of 113 patients with OpSCC, 80 % of patients were current smokers, including 75 % of patients with Hpv-positive tumor status. men with OpSCC were statistically significantly more likely to smoke than women (p = 0.001), as were men with Hpv-positive tumor (p = 0.015). Smoking patients were characterized by a larger size of the primary tumor (T3–4), including those with Hpv (p = 0.015). positive Hpv status of the tumor is associated with autoimmune diseases (autoimmune thyroiditis, psoriasis) (p ˂ 0.05). A high level of TILs is characteristic of smokers, including those with p16+-status (p ˂0.05), but not for all patients with this status. The positive expression of ERα is associated with p16+-status, and the latter is associated with the absence of p53 expression (p ˂0.05). During conservative therapy, tumor regression is associated with the primary tumor size T1–2, p16 + status, female sex, age less than 55 years, TILs level ≥ 57.5 %, pD-L1 expression levels on tumor cells ≥2.2 %, Bcl-2 ≥5 % and ERα ≥65 % (p ˂ 0.05). At the same time, quality of good predictive model for tumor regression showed a TILs level of ≥57.5 % (area under curve, AuC) 0.796; sensitivity 78.6 %; specificity 75 %) and ERα (AuC 0.725; sensitivity 65 %; specificity 83 %). The level of motivation to quit smoking ranged from 1 to 7 points according the 10-point motivation scale in 89 % of respondents. Only 10 patients were ready to quit smoking immediately (10 points on the motivation scale). Conclusion. Molecular heterogeneity of OPSCC was revealed, including in the group of p16+-tumors. Correlation of clinical and molecular parameters with response to conservative therapy can be used in planning of primary therapy and earlier use of surgical treatment. The level of motivation to quit smoking in patients with squamous cell carcinoma of the head and neck may be increased by drawing attention to the problem at each doctor’s appointment as well as by informing about how to quit smoking and therapeutic approaches. In unmotivated patients, the concept of reducing the harm of smoking can be used involving the replacement of cigarettes with electronic tobacco heating systems, eliminating the carcinogenic effect of its combustion products.

Molluscum Contagiosum: Case Report in A 10-Year Period (2008-2017)

OBJECTIVE. We present a series of 10 cases of Molluscum contagiosum (MC) in a 10-year period (2008-2017). Over 51,342 consultations during these years, they represent 0.01% of the total. The average age was 38 years. The average parity was 0.7 (but 50% are nulliparous). They presented multiple lesions on the vulva, perineum, buttocks, inner thighs, and/or suprapubic area. The objective of the study is to compare the progression of the disease with and without treatment. MATERIALS AND METHODS. Anamnesis, clinical examination, and photography were performed with the informed consent of the patients. RESULTS. In 3 cases, there was abnormal vaginocervical cytology (ASCUS, LSIL) associated with positive HPV. 5 cases did not receive any treatment, and the lesions disappeared before one year (7 months on average). 5 of the cases were treated with imiquimod, and the lesions resolved in 5 months on average. However, they required several treatments. CONCLUSION. MC is considered a low-frequency STD. It is the visual aesthetics rather than the symptoms that bother the most.

Update: Epidemiology and Prevention of Oropharyngeal Cancer

Due to the association with the causal HPV-16 infection, the oropharyngeal carcinoma spreads into two separate entities depending on HPV-16 positivity. More recent data show a diversified picture of the importance and prevalence of the surrogate parameter p16 (discordance) for a definitive HPV-16 association, which varies worldwide. In the context of prevention options, vaccination is of major and HPV screening of healthy people only of little importance.

Abstract 1769: Pan-cancer genomic characterization of human papillomavirus associated tumors reveals patterns of somatic alteration that associate with virus status and anatomic site

Abstract Human papilloma virus (HPV) infection causes over 600,000 human cancers yearly and accounts for nearly all cervical cancers, increasing rates of head and neck squamous cell carcinomas (HNSCC), and many anogenital cancers - all with varying clinical outcomes due to a lack of personalized care. While recent integrative genomic studies have described molecular features of individual cancer types, few studies have compared genomic changes between HPV(+) and HPV(-) cancers across anatomic sites. Here, we conducted the first pan-cancer genomic analysis of HPV-associated tumors across multiple anatomic tumor types using whole exome and transcriptome data from The Cancer Genome Atlas (TCGA) cohorts of cervical (n=254) and HNSCCs (n=514), and targeted exome sequencing of 800 cancer genes plus full length HPV16/18 genomes in a clinical cohort of squamous tumors from the head and neck (n=458), cervix (n=78), vulva (n=23), anal canal (n=5), and vagina (n=2). Somatic variant calling and filtering, followed by an integrative pathway analysis of commonly altered targets, defined the catalog of somatic mutations and copy number alterations (CNAs) that drive HPV(+) and HPV(-) tumorigenesis. Sequencing reads from viral RNA or DNA determined HPV status, and HPV type, genome structure, integration events, and viral load were characterized in a subset of samples via de novo assembly of viral aligned reads followed by copy number analysis, breakpoint identification, and the calling of structural variants. Overall HPV positivity was 50% (668 out of 1334 total), with HPV16 accounting for 96%, 89%, and 60% of all HPV(+) anogenital, head and neck, and cervical tumors respectively. Significant differences in somatic mutation frequency between HPV(+) and HPV(-) tumors were observed in the full cohort, as well as in analyses stratified by anatomic site. Interestingly, we noticed recurrently mutated “hotspots” attributable to increased APOBEC-mutagenesis in HPV(+) samples across anatomic sites (PIK3CA:E545K, FGFR3:S249C, EP300:D1399N), while hotspot mutations likely caused by tobacco smoking predominate HPV(-) HNSCC (PIK3CA:H1047R/L, CDKN2A:R80*, TP53:R282W). Focal and arm level CNAs were distinctive, including gains of 11q22 in HPV(+) cervical and HPV(-) HNSCC, and losses of 11q22 in HPV(+) HNSCC. Biological pathways commonly altered include epithelial differentiation, cell death, innate immunity, growth factor/kinase signaling, and cell cycle control. In summary, pan-cancer genomic analysis revealed distinct patterns of somatic alteration of conserved biological pathways that associate with HPV status and anatomic site. These findings improve our understanding of tumor biology unique to HPV-associated cancers and may lead to novel treatment and classification strategies to improve patient outcomes in the clinical setting. Citation Format: Jeremiah Ray Holt, Paul Little, Heejoon Jo, Xiaobei Zhao, Hyo Young Choi, Vonn Walter, Benjamin Wahle, Jose P. Zevallos, Angela Mazul, Katherine A. Hoadley, Michele Hayward, David N. Hayes. Pan-cancer genomic characterization of human papillomavirus associated tumors reveals patterns of somatic alteration that associate with virus status and anatomic site [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1769.

Abstract 6413: Biomarkers of response and progression to Pembrolizumab and Vorinostat combination in late-stage squamous cell carcinoma patients of different locations included in the PEVOsq basket trial

Abstract Background: Epigenetic modulation plays a major role in escaping tumor immunosurveillance. PEVOsq (NCT04357873) was an open-label, non-randomized, multi-center, basket phase II trial evaluating the efficacy of pembrolizumab (P) and the vorinostat (V) HDAC inhibitor in 112 patients (pts) with recurrent and/or metastatic squamous cell carcinoma (SCC) of the cervix, head and neck, anus, vulva/vagina, penis, and lung. Results showed an objective response rate (ORR) of 25%, the highest being in anal (31%) and cervical (39%) (ASCO #397612). We report here early biomarkers of response and progression to P+V. Patients and Methods: Pts had to undergo a tumor biopsy at baseline, and optional biopsies on-treatment (after cycle 2), and at progression for translational analyses. PD-L1 expression (n=102), tumor-infiltrating lymphocytes quantification (n=39), HPV typing (n=111), WES (n=83), RNAseq (n=82) and liquid chromatography-mass spectrometry (LC-MS) quantitative analysis of histone post-translational modifications (PTMs) (n=44) were performed on baseline samples.SNVs, CNVs, TMB, MSI status (by MSI sensor), aneuploidy score (AS), mutational signatures, immune signatures, and histone modifications were correlated with response and progression. Results: Sixty-six pts were HPV+ (59%). Most frequently altered genes were PIK3CA (30%), TP53 (30%), KMT2D/C (18 and 17%), and FGF3/4 (17%). MSI was detected in 4 pts (5%), and TMB-high (&amp;gt;10mut/Mb) in 13 pts (16%). High AS (&amp;gt;10) was detected in 34 pts (40%), and was significantly associated with HPV- status (p=0.03). TMB high and MSI were associated with MMR mutational signatures (p&amp;lt;0.01). TMB high was also associated with APOBEC (p=0.02) and DNA polymerase (POL) signatures (p &amp;lt;0.01). Biomarkers associated with improved overall survival (OS) included HPV positivity (7.8 months versus 17.4 months, p&amp;lt;0.01), high TMB (not reached versus 10.3 months, p=0.01), and high PD-L1 CPS score (13.2 months versus 7.0 months, p=0.06).Deconvolution of immune cell infiltration showed an expected trend for increased CD8 and decreased neutrophil infiltration in non progressor pts.Interestingly, LC-MS histone PTMs profiling showed a significant decrease in H4K5K8K12K16-4ac (p=0.05) and increase in H3K27me2K36me1 in non progressor pts (p=0.03). At the transcriptomic level, although not statistically significant, we observed modulation in the expression of genes associated with H3K36me1 (KDM2A, SETD3, SMYD2), and H3K27me3 (KDM6A) regulation, as well as HDAC genes. Conclusions: HPV+ status was associated with improved OS, together with a high TMB and PD-L1 expression. CD8, macrophages and neutrophil signatures at baseline were associated with response. Promising epigenetic biomarkers were identified using LC/MS and will be correlated to transcriptomic and genomic data. Citation Format: Christophe Le Tourneau, Luca Mazzarella, Bastien Cabarrou, Miguel Francisco, Célia Dupain, Maral Halladjian, Gianmaria Frige, Bruno Duso, Yinxiu Zhan, Elena Guerini-Rocco, Roberta Noberini, Tiziana Bonaldi, Maria Manuela Tonini, Grégoire Marret, Clélia Coutzac, Elodie Coquan, Mathilde Saint-Ghislain, Olivia Le Saux, Laetitia Chanas, François Legrand, Daria Maria Filippini, Emmanuelle Jeannot, Stephan Bernhart, Gabor Balogh, Marta Jimenez, Thomas Filleron, Nicolas Servant, Maud Kamal. Biomarkers of response and progression to Pembrolizumab and Vorinostat combination in late-stage squamous cell carcinoma patients of different locations included in the PEVOsq basket trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6413.

Abstract 3014: Exploring the correlation between oncogenic viruses and BRCA1/2gene mutations in Egyptian breast cancer patients

Abstract Background: Recognizing the complexity of viral carcinogenesis and its perspectives, we aimed to investigate one of the key genetic factors associated with breast cancer development, BRCA1,2 mutations, and its association with the presence of some oncogenic viruses like HPV, MMTV, and EBV DNAs in both blood and tissues of breast cancer (BC) patients, hoping to provide new insights on role of oncogenic viruses in cancer development. Patients and Methods: This study was conducted on 84 tissues and blood samples from Egyptian BC women and 50 blood samples from controls without known oncological disease. All samples were tested for the presence of viral DNAs, using real-time PCR assay. Fifty-five BC patients were investigated for the presence of mutations in exons 6 and 9 of BRCA1, and exons 11, 14, and 27 of BRCA2 using a high-resolution melting (HRM) assay. Results were correlated with the clinicopathological characteristics of BC. Results. HPV, MMTV, and EBV DNAs were detected in 30(35.7%), 19(22.6%), and 23 (27.3%) of tissues obtained from 84 BC patients, respectively, and into 16 (19%), 14 (16.7%) and 0 (0%) of blood from the same patients, respectively. On the other hand, these viruses were detected in 0 (0%), 7 (14%), and 0 (0%) of blood specimens obtained from 50 normal controls, respectively. Among 55 BC patients, mutations were detected in 37 (67%) of the tested exons of BRCA1/2 genes in the blood of BC patients, divided as 7 (12.7%) for exons 6 and 9 of BRCA1 gene, and into 11 (20%), 3 (5.5%), and 9 (16.4%) for exons 11, 14 and 27 of BRCA2 gene. Our previous investigation based on NGS showed that pathogenic mutations were (G509A:p.R170Q and c.C1471T:p.Q491X) for exons 6, 9 of BRCA1, respectively, and were (cT4001A: p.L1334X, c.7231delA: p.T2412Lfs and c.T9861A: p.C3287x) for exons 11, 14 and 27 of BRCA2, respectively. Further analysis showed that half of the patients with positive HPV DNA in tissues had mutations in the tested exons of BRCA1/2 genes. In contrast, none of the patients with MMTV DNA (15/55 (27%)) in their tissues had mutations in exons 6 and 9 of BRCA1 and only one patient had a mutation in exons 11 of BRCA2. Regarding EBV, 35% of positive patients had mutations in the tested exons of the BRCA1 gene and 21% in the tested exons of BRCA2 gene. Results were not affected by clinicopathological parameters. Conclusion: MMTV DNA followed HPV, and then EBV DNAs were detected in more than 80% of our BC patients. HPV was the most frequent virus among BC patients showed to be associated with BRCA1/2 mutations in the tested exons. Sequencing analysis is in progress. Understanding this association will provide a relevant implication for developing novel, and personalized therapeutic options for treatment of oncogenic viruses. Citation Format: Samah Loutfy, Rania Abdulmonem Al Najar, Sarah ElSayed, Nasra Abdel Fattah, Ayman Abdel-Samie Gaber, Tarek Hashem, Wafaa S. Khalaf, Ahmed F. Basyony, Amany El-Sharif, Sahar Mohamed Ramzy Radwan, Mohamed Eltokhy. Exploring the correlation between oncogenic viruses and BRCA1/2gene mutations in Egyptian breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3014.

Long-Term Follow-Up Outcomes in Women with In Situ/Microinvasive Adenocarcinoma of the Uterine Cervix Undergoing Conservative Treatment-Cervical Adenocarcinoma Study Group Italian Society of Colposcopy and Cervico-Vaginal Pathology.

The present study aimed to assess long-term follow-up outcomes in women with in situ/microinvasive adenocarcinoma (AC) of the uterine cervix treated conservatively. Retrospective multi-institutional study including women with early glandular lesions and 5-year follow-up undergoing fertility-sparing treatment. Independent variables associated with recurrence were evaluated. Logistic regression analysis and Kaplan-Meier survival analysis with Logrank test were performed. Of 269 women diagnosed with in situ/microinvasive AC, 127 participants underwent conservative treatment. During follow-up, recurrences were found in nine women (7.1%). The only factor associated with recurrence during follow-up was positive high-risk Human Papillomavirus (hr-HPV) testing (odds ratio 6.21, confidence interval 1.47-26.08, p = 0.012). HPV positivity in follow-up showed a recurrence rate of 21.7% against 3.8% in patients who were HPV-negative (p = 0.002, Logrank test). Among women with negative high-risk HPV tests in follow-up, recurrences occurred in 20.0% of non-usual-type histology vs. 2.1% of usual-type cases (p = 0.005). HPV testing in follow-up is of pivotal importance in women with early glandular lesions undergoing conservative treatment, given its recurrence predictive value. However, women who are high-risk HPV-negative in follow-up with non-usual-type histopathology may represent a sub-population at increased risk of recurrences. Further studies should confirm these findings.

History of HPV in HPV-positive elderly women

BackgroundThe aim of this study was to examine the natural course of HPV infection in women of 60 years and older who were HPV positive at inclusion, and any association between HPV positivity in historical samples and dysplasia outcome. MethodsEighty-nine women aged 60–82 years, who tested positive for HPV between 2012 and 2016 were included. Sampling for cytology and/or histology was also performed. HPV genotyping was carried out on archived material back to 1999. ResultsOf the 89 HPV-positive women 16 had HSIL, 34 had LSIL and 39 were benign at inclusion. Of the women with HSIL, 50.0% had the same HPV type in the archive samples, 12.5% had another type, and 37.5% were HPV negative. Among the 34 women with LSIL, 47.1% had the same HPV type in archive samples, 5.8% had another type, and 47.1% were HPV negative. Of the 39 women without dysplasia at inclusion, 25.6% had the same HPV type in archive samples, 5.1% had another HPV type and 69.2% were HPV negative. ConclusionSurprisingly few of the elderly women thus seem to have a history with the same or any HPV infection the years before being diagnosed with an HPV infection and dysplasia. The significance of an HPV infection for dysplasia development in elderly women is still not fully understood.

A population based study on human papillomavirus infection and associated risk factors among women of the remote South Andaman Island, India

BackgroundHuman papillomavirus (HPV) is associated with cervical cancer and cervical dysplasia worldwide. Data on HPV prevalence in a region is important because it serves as a predictor of the likelihood of the population in that particular region acquiring cervical cancer. Moreover, with the availability of effective vaccines, the public health system must be aware of the preponderance of HPV to implement the vaccine. The present study was designed to understand the prevalence of HPV and associated factors among the women of South Andaman Island.MethodsA cross-sectional study was conducted among married women of reproductive age (18–59 years) from South Andaman District from 2018 to 2022. Cervical scrapes were collected from participants after obtaining informed written consent for HPV molecular testing (HPV DNA) such as PCR assay. Demographic data was collected using a standard questionnaire and statistical analyses were performed to determine the associated factors.ResultsThe study showed prevalence of HPV as 5.9%(95% CI: 3.9–7.9) and prevalence of HR-HPV16 was 4.1% (95% CI 2.6 – 5.5) and HR-HPV18 prevalence was 1.8(95% CI: 0.6–3). The independent factors associated the HPV positivity were age above 55 years, menopause, post-menopausal bleeding, blood-stained vaginal discharge and loss of weight. Age was associated with all HPV infections among the South Andaman women.ConclusionsHPV 16 was reported as the predominant high risk HPV type circulating among women of South Andaman. Cervical cancer and precancerous lesions were significantly associated with HPV positivity and High risk HPV 16. Based on the knowledge of the risk factors associated with HPV, implementation of stronger public health awareness and prophylactic HPV vaccination is crucial among the women of this remote island.

The Role of β1 Integrin/CD29 as a Potential Prognostic Factor for the Risk of Progression to Cervical Carcinoma in HPV-Associated Lesions.

Background and Objectives: Available evidence reports the overexpression of β1 integrin in dysplastic rather than normal cervical tissue. We aimed to evaluate the involvement of β1 (CD29) integrin in the progressive pathogenesis of cervical intraepithelial neoplasia (CIN). Materials and Methods: From January 2019 to December 2021, we prospectively enrolled women undergoing a colposcopy with a cervical biopsy for abnormal cervical cytology and/or undefined cytology with a positive HPV DNA test and women with relapsing cervical inflammatory disorders. Based on the histopathological results, women were divided into four groups: group A (CIN1), group B (CIN2), group C (CIN3), and group D (no CIN diagnosis) as a control group. Subsequently, cytofluorimetry and immunohistochemical analysis (based on the identified positive cell ratios as follows: ≤10%, negative; 10-25%, 1+ (weak); 25-50%, 2+ (medium); ≥50%, and 3+ (high)) for β1 integrin were carried out. Results: In total, 154 women were included. The average fluorescence intensity in the four groups was 2.35 ± 1.37, 2.73 ± 1.56, 3.09 ± 1.56, and 2.13 ± 1.25 UA from groups A to D, respectively; this figure was significantly different for CIN3 (group C) women relative to the other groups (p = 0.0132). Higher β1 integrin/CD29 concentrations in the CIN groups with HR-HPV 16 and 18 were also detected (p = 0.0292, 0.0367, and 0.0357 respectively for CIN3, CIN2, and CIN1). Immunohistochemistry analysis showed higher results for the CIN3 group compared to controls and all the other groups (p < 0.001). Conclusions: β1/CD29 integrin expression increased with CIN grade, and it was significantly higher in CIN3 lesions. This could be used as a promising screening tool to identify women prone to developing high-grade cervical lesions. However, additional evidence is needed to strengthen these findings.

Direct mailing of HPV self-sampling kits to women aged 50-65 non-participating in cervical screening in the Czech Republic.

A population-based cervical cancer screening programme is implemented in the Czech Republic. However, participation is insufficient among women over 50 years. This study aimed to estimate the potential improvement in participation through directly mailed HPV self-sampling kits (HPVssk) compared with standard invitation letters in women aged 50-65 non-participating in screening. The study recruited 1564 eligible women (no cervical cancer screening in the last 3 years or more, no previous treatment associated with cervical lesions or cervical cancer). Eight hundred women were mailed with an HPVssk (HPVssk group), and 764 women were sent a standard invitation letter (control group) inviting them to a routine screening (Pap test). The primary outcome was a comparison of the overall participation rate between study groups using a binominal regression model. The participation rate in the HPVssk group was 13.4% [95% confidence interval (CI) 11.2-15.9%; 7.4% of women returned the HPVssk and 6.0% attended gynaecological examination] and 5.0% (95% CI 3.6-6.8%) in the control group. Using the binominal regression model, the difference between the groups was estimated as 7.6% (95% CI 5.0-10.2%; P < 0.001). In the HPVssk group, 22% of women who returned HPVssk had a positive result and 70% of them underwent a follow-up examination. Compared with traditional invitation letters, the direct mailing of the HPVssk achieved a significantly higher participation rate, along with a notable HPV positivity rate among HPVssk responders. This approach offers a potentially viable method for engaging women who have not yet attended a cervical screening programme.

High rate of non-vaccine targeted high-risk HPV genotypes circulate among women in Eastern Ethiopia

The World Health Organization [WHO] recommends a genotype-specific human papillomavirus [HPV] vaccination as a primary prevention strategy to control the burden of cervical cancer globally. In Ethiopia, where the non-vaccine-targeted HPV genotypes have not been adequately studied, a vaccination initiative was launched in 2018 targeting HPV-6,-11, -16, and -18 for girls aged 14–18 years. The co-existence of both vaccine-targeted and non-targeted genotypes is a serious concern, as it can accelerate cancer progression. Therefore, this study was conducted to determine the prevalence of non-vaccine-targeted HPV genotypes and assess the level of multiple infections with other genotypes in eastern Ethiopia. A health facility-based cross-sectional study including 110 women with positive HPV DNA results was conducted from April to August 2021. A structured questionnaire to collect demographic and clinical data was used. Cervical swabs were collected using L-shaped FLOQSwabs. Women's cytological profile was determined based on Pap smear test results. An automated nucleic acid extraction system using STARMag 96 ProPrep Universal Extraction Kit was utilized following the manufacturer's protocol. An amplification assay in real-time was employed to amplify and identify the HPV Late 1 [L1] gene, which is utilized for genotyping purposes. Following this, the collected data was entered into Epi data version 3.1 software, and the analysis was performed using STATA version 14. A total of 110 women [age range 30–60 years, mean age = 36.5 years and SD ± 6.9] had positive HPV DNA results and were included in the study. Among these, 108 women had valid co-testing [Pap test and HPV DNA test] results for further analysis, and the results of the remaining 2 women were rejected. Overall, the prevalence of non-vaccine-targeted HPV was 56 (51.8%, 95%CI [0.42, 0.61]), of which 28 women (25.4%, 95%CI [0.18, 0.34]) had a single non-vaccine HPV genotype infection. The remaining 29 women (26.4%, 95% CI: 0.190–0.355) experienced multiple infections. The non-vaccine-targeted genotypes of HPV-35 accounted for 11 cases (10%, 95%CI [0.06, 0.17]), HPV-68 was detected in 9 women (8.2%, 95%CI [0.04, 0.15]), HPV-56 and HPV-66 were both found in 8 cases each (7.3%, 95%CI [0.04, 0.14]) of the total. In addition, out of these 108 women, 93 (86.1%, 95%CI [0.78, 0.91]) had low-grade squamous intraepithelial lesions, 13 (12%, 95%CI [0.07, 0.20]) no intraepithelial lesion or malignancy, and two (1.9%, 95%CI [0.01, 0.07]) high-grade squamous intraepithelial lesions. Furthermore, there was no statistical difference [p = 0.755] between vaccine-targeted and non-vaccine-targeted genotypes as the primary cause of cervical lesions. In conclusion, the findings of the present study highlight the existence of a notable prevalence of multiple infections caused by non-vaccine-targeted HPV genotypes. Therefore, it is recommended that both the Federal and regional health bureaus to evaluate the range of hr HPV genotypes protected by the current HPV vaccine and explore the option of transitioning from the quadrivalent HPV vaccine to a novavalent vaccine that includes seven high-risk HPV genotypes.

Biomarkers of pembrolizumab efficacy in advanced anal squamous cell carcinoma: analysis of a phase II clinical trial and a cohort of long-term responders

BackgroundRecent trials suggest that programmed cell death 1 (PD-1)-directed immunotherapy may be beneficial for some patients with anal squamous cell carcinoma and biomarkers predictive of response are greatly needed.MethodsThis multicenter...

Colposcopic biopsy findings in ASCUS or normal cervical cytology patients with high-risk HPV positivity

Colposcopic biopsy findings in ASCUS or normal cervical cytology patients with high-risk HPV positivity

Quality of food intake and spontaneous clearance of Human papillomavirus in women.

Human papillomavirus is known to be the main cause of cervical cancer. Given that cervical cancer is still one of the leading causes of death in women of reproductive age, it is very important to prevent HPV infection and its persistence. The aim of our study was to explore the quality of the diet in the spontaneous clearance of cervical HPV infection and its persistence. Furthermore, we have assessed the associations of overall diet quality and dietary components with HPV occurrence and clinical resolution of HPV over time. 200 women of age between 20 and 68 years were included in this prospective study. Patients were tested for the presence of HPV subtypes, and were given questionnaires about their dietary habits. 43 patients were positive for HPV virus, and 157 patients were negative. Among the positive HPV patients, the mean value (±SEM) of the score was 12.88±0.6822 (min=7, max=21) with upper CI of mean 14.26 and coefficient of variation of 34.72%. Various antioxidants have different abilities to influence the course of HPV-mediated cervical cancer. This study showed that women who did not consume fruits, and dark-green vegetables had ahigher risk of HPV infection (Tab. 2, Fig. 3, Ref. 40): Text in PDF www.elis.sk Keywords: cervical cancer, human papillomavirus, folate, vitamin D3, dietary intake.

Clinical value of optical coherence tomography in the early diagnosis of cervical cancer and precancerous lesions: a cross-sectional study.

This study aimed to measure the accuracy of optical coherence tomography (OCT) in the early diagnosis of high-grade cervical lesions and assess its diagnostic value in the triage of high-risk HPV infection. From Jan 2019 to Jan 2021, women who visited the gynecology clinics of 2 hospitals for colposcopy were invited to participate in this study. Women aged 35 to 64 years old who were sexually active and had an intact cervix with a diameter of more than or equal to 2cm were included in this study. Additionally, individuals with abnormal cytology, positive HPV test results, or other clinically suspicious symptoms or signs were referred. All participants were examined before colposcopy using OCT. Biopsy and/or ECC were conducted under colposcopy. We used the results of histopathology as the gold standard and assessed the accuracy of OCT. Overall, 883 women were included in the analysis. Approximately 13.25% of women were ASCUS+ in cytological assessments, and 22.31% were positive for high-risk HPV. Nearly 15.18% of women were positive in OCT. Of them, 27 women were diagnosed with CIN2, and 33 were diagnosed with CIN3+ lesions. Among HPV-positive women, the detection rates for CIN2+ and CIN3+ were much lower for those who were negative in OCT, compared with NILM cytology (CIN2+: 20.0% vs. 30.0%, P=0.002, and CIN3+: 18.2% vs. 27.3%, P=0.013). Among women who were positive for HPV16/18, the detection rate for CIN2+ was much lower for negative OCT, compared with NILM cytology (8.3% vs.15.0%, P=0.005). Compared to HPV and cytological tests, HPV combined with OCT had higher specificity for detecting CIN2+ and CIN3+ (96.1% vs. 93.2%, P=0.002; 93.8% vs. 91.3%, P=0.013). OCT triage after HPV genotyping had the highest AUC for detecting CIN2+ and CIN3+ cases among patients with high-risk HPV infection (0.921, 0.920). OCT is an accurate test for the early diagnosis of high-grade cervical lesions and has great diagnostic value in the triage of patients with high-risk HPV infection.

Effect of HPV Vaccination on Virus Disappearance in Cervical Samples of a Cohort of HPV-Positive Polish Patients.

The introduction of human papillomavirus vaccines revolutionized cervical cancer prevention. Our research hypothesis is that HPV vaccination affects the remission of HPV in cervical swabs. We provide a prospective, ongoing, 24-month, non-randomized study in HPV-positive women. We enrolled 60 patients with positive HPV swabs from the cervix (fifty-one vaccinated with the nine-valent vaccine against HPV and nine unvaccinated). Using an enzyme-linked immunosorbent assay, we determined IgG class antibodies of HPV in the patients' serums. Persistent HPV infection after vaccination was significantly less frequent in the nine-valent vaccinated group (23.5%) compared to the control group (88.9%; p < 0.001). Antibody level after vaccination was significantly higher in the vaccinated patients compared to the control group. The reactive antibody level was seen in the case of all patients in the vaccinated group and one-third of the unvaccinated group (33.3%, n = 3). The vaccination of HPV-positive patients may increase the chance of HPV remission in cervical swabs and may be a worthwhile element of secondary prevention in HPV-positive patients.