HPV Types 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.

Current status of high-risk HPV infection and correlation with multiple infections in cervical lesions in Western Guangzhou.

This study aims to investigate the current status of multiple HPV infection and its association with cervical lesions in the western region of Guangzhou. A retrospective analysis of clinical data from cervical cancer screening patients was conducted. The patients were grouped based on HPV genotypes and cervical pathology results to explore the prevalence of high-risk HPV infection and its relationship with cervical lesions in the western region of Guangzhou. The study also analyzed the relationship between high-risk HPV infection and cervical lesions among different age groups. A total of 13,060 patients were included in the study, with an overall infection rate of 18.46% (2,411/13,060). Among them, the infection rate of HPV genotype 16 was 14.14% (341/2,411), HPV genotype 18 was 5.23% (126/2,411), and other 12 high-risk HPV genotypes accounted for 71.96% (1,735/2,411). When comparing the incidence of HSIL+ (high-grade squamous intraepithelial lesion or worse) among different HPV genotypes, the results showed that the HPV 16 infection group (47.50%) had a higher incidence than the HPV 18 infection group (25.40%) and the other 12 high-risk HPV genotypes group (15.97%; P < 0.05). In the multiple infection groups, the pathogenicity rates were 63.64% (7/11) for the 16+18 HPV infection group, 42.97% (55/128) for the 16+other 12 high-risk HPV genotypes infection group, 26.79% (15/56) for the 18+other 12 high-risk HPV genotypes infection group, and 57.14% (8/14) for the 16+18+other 12 high-risk HPV genotypes infection group. These rates were significantly different compared to the single infection group (P <0.01). Although there was no statistically significant difference in the incidence of cervical cancer between the HPV 16 infection group and the HPV 18 infection group, both groups had a higher incidence compared to the group with other 12 high-risk HPV genotypes infection (P < 0.05). Further analysis suggests that the severity of cervical lesions is not associated with the number of high-risk HPV infections, i.e., the severity of cervical lesions is unrelated to multiple HPV infections but is instead related to the pathogenicity of the HPV genotypes. The infection rate and multiple HPV infection rate of women under 35 years old were higher than those of women aged 35 and above (20% vs. 17.1%; 2% vs. 1.3%; P < 0.05). Moreover, the pathogenicity rate of HSIL+ among high-risk HPV infection increased with age. In the western region of Guangzhou, the overall infection rate of high-risk HPV is 18.46%. The severity of cervical lesions is unrelated to multiple HPV infections. The fundamental reason is the distinct pathogenicity of different HPV genotypes. The HSIL+ pathogenicity rates, from high to low, are in sequence for HPV 16, HPV 18, and the other 12 HPV types.

Pattern of multiple human papillomavirus infection and type competition: An analysis in healthy Chinese women aged 18–45 years

ABSTRACT To assess the pattern of multiple human papillomavirus infection to predict the type replacement postvaccination. A total of 7372 women aged 18–45y from a phase III trial of an Escherichia coli-produced HPV-16/18 vaccine were analyzed at enrollment visit before vaccination. Hierarchical multilevel logistic regression was used to evaluate HPV vaccine type and nonvaccine-type interactions with age as a covariate. Binary logistic regression was construed to compare multiple infections with single infections to explore the impact of multiple-type infections on the risk of cervical disease. Multiple HPV infections were observed in 25.2% of HPV-positive women and multiple infections were higher than expected by chance. Statistically significant negative associations were observed between HPV16 and 52, HPV18 and HPV51/52/58, HPV31 and HPV39/51/52/53/54/58, HPV33 and HPV52/58, HPV58 and HPV52, HPV6 and HPV 39/51/52/53/54/56/58. Multiple HPV infections increased the risk of CIN2+ and HSIL+, with the ORs of 2.27(95%CI: 1.41, 3.64) and 2.26 (95%CI: 1.29, 3.95) for multiple oncogenic HPV infection separately. However, no significant evidence for the type-type interactions on risk of CIN2+ or HSIL+. There is possibility of type replacement between several pairs of vaccine and nonvaccine HPV type. Multiple HPV infection increased the risk of cervical disease, but coinfection HPV types seem to follow independent disease processes. Continued post-vaccination surveillance for HPV 51/52/58 types and HPV 39/51 types separately was essential after the first and second generation of HPV vaccination implementation in China.

Lineage Replacement and Genetic Changes of Four HR-HPV Types during the Period of Vaccine Coverage: A Six-Year Retrospective Study in Eastern China.

This study aimed to provide clinical evidence for lineage replacement and genetic changes of High-Risk Human Papillomavirus (HR-HPV) during the period of vaccine coverage and characterize those changes in eastern China. This study consisted of two stages. A total of 90,583 patients visiting the Obstetrics and Gynecology Hospital of Fudan University from March 2018 to March 2022 were included in the HPV typing analysis. Another 1076 patients who tested positive for HPV31, 33, 52, or 58 from November 2020 to August 2023 were further included for HPV sequencing. Vaccination records, especially vaccine types and the third dose administration time, medical history, and cervical cytology samples were collected. Viral DNA sequencing was then conducted, followed by phylogenetic analysis and sequence alignment. The overall proportion of HPV31 and 58 infections increased by 1.23% and 0.51%, respectively, while infection by HPV33 and 52 decreased by 0.42% and 1.43%, respectively, within the four-year vaccination coverage period. The proportion of HPV31 C lineage infections showed a 22.17% increase in the vaccinated group, while that of the HPV58 A2 sublineage showed a 12.96% increase. T267A and T274N in the F-G loop of HPV31 L1 protein, L150F in the D-E loop, and T375N in the H-I loop of HPV58 L1 protein were identified as high-frequency escape-related mutations. Differences in epidemic lineage changes and dominant mutation accumulation may result in a proportional difference in trends of HPV infection. New epidemic lineages and high-frequency escape-related mutations should be noted during the vaccine coverage period, and regional epidemic variants should be considered during the development of next-generation vaccines.

Prevalence of Genotype Patterns Associated With High-Risk Human Papillomavirus in Cervical Lesions.

Background Cervical lesions, often linked to high-risk human papillomavirus (HR-HPV) infection, pose a significant public health concern globally. Human HPV is considered the principal etiological factor in the development and transformation of pre-malignant lesions of the cervix leading to cervical carcinoma. The global distribution of HPV genotypes exhibits significant variability, liable to be influenced by the intricate interplay of geographical and biological factors among different HPV types and host immunogenetic elements. Owing to limited research addressing the genotypic distribution of HR-HPV in females with cervical lesions in the western zone of India, this study aims to bridge this gap by providing the prevalence of HR-HPV genotypes in women diagnosed with cervical lesions in this zone. Methodology This observational, cross-sectional study was performed in the Laboratory for Genotype Detection in the western zone of India. The study population comprised a total of 215 females in the age range of18 to 60 years. A thorough examination of clinical specimens was conducted employing molecular techniques for HPV genotyping using TRUPCR® HPV-HR with a 16/18 Genotyping Kit.DNA Extraction was done using 3B Blackbio Biotech India Ltd. as per the standard protocol. The statistical analysis was performed using SPSS version 28 (IBM Corp., Armonk, NY, USA), and continuous variableswere compared usingStudent's t-test. Results The overall prevalence of HR-HPV in women with cervical lesions in the western zone of India was 62.32% (134/215). The most prevalent genotype was HPV16 at 92/134 (68.65%), followed by HPV18 at 33/134 (24.62%) and HPV52 at 9/134 (6.7%). The overall prevalence of single type was 56.71% (76/134). The most prevalent genotype combination after HPV18 + 59 (29.85%) at 40/134 was HPV52 + 39 + 51 (13.43%) at 18/134. HR-HPV infection was found to be significantly (p < 0.05) associated with factors such as having three or more children, having a lower socioeconomic status, residing in rural areas, and being in a pre-menopausal stage. Conclusions This study focused on assessing the prevalence of the genotypes associated with HR-HPV infection, providing valuable insights into the epidemiology of cervical lesions in the western zone of India. The findings revealed high-risk genotype HPV16 to be the most prevalent type, followed by HPV18 and HPV52. The most prevalent genotype combinations were HPV18 + 59 and HPV52 + 39 + 51. The results of the study would potentiate the wealth of epidemiological data related to HPV infection in cervical lesions and could be employed for guiding future interventions and preventive strategiesthrough orientation programs.

Next generation of mRNA and lncRNAs based-vaccines platforms: Highlighted for HPV in head and neck squamous cell carcinoma, cervical and colorectal cancers and oncogenic viruses HBV/HCV in hepatocellular carcinoma

More than 200 HPV genotypes and several HPV types associated with particular diseases as oral lesions (Hecks disease, oropharyngeal carcinoma, laryngeal papillomas), anogenital warts (Bowenoid papulosis, Buschike‒Lowenstein tumor), Epidermodysplasia verruciformis (plane warts, Pityriasis‒ like plaques, squamous cell carcinomas of sun‒exposed skin) have been described. Several advances in the genomics era and the development of new technological tools for next-generation sequencing have been showed that approximately 98% of RNAs are not translated into proteins. This study aims to succinctly describe long non-coding RNAs (lncRNAs) and their correlation with the hallmark of cancers since they comprise a class of RNAs that do not code for proteins. Oncogenic mutations occur with higher prevalence in non-coding regions, and the correlation of lncRNAs is extremely important for better understanding the biology of cancer cells as well as elucidating the molecular mechanisms underlying cancer. Thus, these may be promising tumor biomarkers and potential therapeutic targets exemplified in hepatocellular carcinoma, cervical and colorectal cancer induced by oncogenic viruses. Future studies are need to delve deeper into the cellular signaling pathways involved in biological processes. This theme addresses innovative issues on the ONU 2030 agenda from the perspective of global one health.

Titanium Dioxide Nanoparticles: A Novel Approach for Inhibiting Human Papillomavirus

Nanotechnology products such as titanium dioxide nanoparticles (TiO2-NPs) can be used for viral infections because of their unique characteristics. The current study aimed to determine the impact of TiO2-NPs on HPV type 1 and 2 infections. The characterization of these NPs was performed using dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), high-resolution transmission electron microscopy (HRTEM), and X-ray diffraction (XRD). The MTT assay was used to determine the toxic impacts of TiO2-NPs on BHK-21 cells. The efficiency of TiO2-NPs was performed using several parameters, including TCID50 and RT-PCR assays. An indirect immunofluorescence assay (IFA) was performed to estimate the inhibitory impact of TiO2-NPs on viral antigen expression, and Acyclovir was used as a reference medicine. When the human papilloma type 1 and 2 viruses exposed to TiO2-NPs at high doses (100 μg/mL) produced 0.3, 1.1, 2.3, and 3.3 log10 TCID50 decreases in infective virus load when compared with control viruses (P&lt;0.0001), these TiO2-NPs doses were related to 24.9%, 35.1%, 47.2%, 59.5%, and 66.6% inhibition percentages that were determined depending on the viral titer as compared to virus control. It is concluded that TiO2-NPs have strong potential for the treatment of face and labial lesions caused by papillomaviruses 1 and 2 and could be used in topical formulations.

Alterations of UHRF family Expression and was regulated by High Risk Type HPV16 in Uterine Cervical Cancer

The altered protein expression of inverted CCAAT box-binding protein of 90 kDa/ubiquitin-like with PHD and RING finger domains 1 (ICBP90/UHRF1), and Np95-like ring finger protein (NIRF)/UHRF2, which belong to the ubiquitin-like with PHD and RING finger domains (UHRF) family, is linked to tumor malignancy and the progression of various cancers. In this study, we analyzed the UHRF family expression in cervical cancers, and it's regulation by human papillomavirus (HPV). Western blotting was performed to analyze protein expression in cervical cancer cell lines. Immunohistochemical analysis were used to investigate the expression of UHRF family and MIB-1 in cervical cancer tissues. Transfection were done for analyze the relationship between UHRF family and HPVs. We showed that NIRF expression was decreased and ICBP90 expression was increased in cervical cancers compared to normal counterparts. Western blotting also showed that NIRF expression was quite low levels, but ICBP90 was high in human cervical cancer cell lines. Interestingly, ICBP90 was up regulated by high risk type HPV16 E6 and E7, but not low-risk type HPV11. On the other hand, NIRF was down regulated by high risk type HPV16 E6 but not by E7. Low risk type HPV11 E6 did not affect the NIRF expression at all. We propose that ICBP90 overexpression, and reduced NIRF expression, found in cervical cancers, is an important event of a cervical carcinogenesis, and especially ICBP90 may offer a proliferating marker and therapeutic target for treating uterine cervical cancers.

Clinical Validation of the Vitro HPV Screening Assay for Its Use in Primary Cervical Cancer Screening.

Many scientific societies have issued guidelines to introduce population-based cervical cancer screening with HPV testing. The Vitro HPV Screening assay is a fully automatic multiplex real-time PCR test targeting the L1 GP5+/GP6+ region of HPV genome. The assay detects 14 high risk (HR) HPV genotypes, identifying individual HPV16 and HPV18 genotypes, and the HPV-positive samples for the other 12 HR HPV types are subsequently genotyped with the HPV Direct Flow Chip test. Following international guidelines, the aim of this study was to validate the clinical accuracy of the Vitro HPV Screening test on ThinPrep-collected samples for its use as primary cervical cancer screening, using as comparator the validated cobas® 4800 HPV test. The non-inferiority analysis showed that the clinical sensitivity and specificity of the Vitro HPV Screening assay for a diagnosis of cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) were not inferior to those of cobas® 4800 HPV (p = 0.0049 and p < 0.001 respectively). The assay has demonstrated a high intra- and inter-laboratory reproducibility, also among the individual genotypes. The Vitro HPV Screening assay is valid for cervical cancer screening and it provides genotyping information on HPV-positive samples without further sample processing in a fully automated workflow.

Abstract 4804: Prevalence of anal HPV infection in women attending a gynecology and colposcopy clinic: Assessing the potential impact of HPV vaccination

Abstract Human papillomavirus (HPV) accounts for over 80% of anal cancer cases. In the effort to prevent HPV-related cancers, the 9-valent HPV vaccine emerged as a crucial intervention, targeting HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58; the previous 4-valent (types 6,11,16,18) and 2-valent (types 16, 18). This study involved 213 women aged 21-50 attending gynecology and colonoscopy clinics in San Juan, Puerto Rico. The study assessed anal HPV prevalence and analyzed vaccination status-related differences. Anal swabs were collected for HPV testing using the ATILA AmpFire, targeting 17 HPV types. This method identified 15 high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, and 68) and two low-risk HPV types (6 and 11). Prevalence of any HPV, HR-HPV, and LR-HPV, and of specific HPV types were calculated by overall and vaccination status. Differences were assessed for statistical significance (p&amp;lt;0.05) using Fisher's exact or Pearson χ2 test. The mean age of women was 36.0 ± 5.9 years. Overall, 19.7% (n=44) had received the HPV vaccine; among them, 52.2% (n=23) had received the 4-valent vaccine, 2.3% had received the 2-valent vaccine, 2.3% had received the 9-valent vaccine, and 43.2% were uncertain about their specific HPV vaccine type. The prevalence of anal HPV infection was 68.5% for any HPV, 61.5% for HR-HPV, and 15.0% for LR-HPV. The most prevalent HR-HPV types were HPV 56 (13.2%), HPV 68 (11.7%), and HPV 66 (11.2%). There were no statistically significant differences in the prevalence of any HPV, HR-HPV, and LR-HPV between vaccinated and unvaccinated women. The most common HR-HPV type among vaccinated were HPV 66 (20.5%), HPV 31 (18.2%), HPV 56 (15.9%), while the most common among unvaccinated women were HPV 56 (12.4%), HPV 68 (12.4%), and HPV 16 (12.4%). Additionally, when evaluating as a grouped variable, the HPV genotypes covered by the 4-valent, unvaccinated women had a significantly higher prevalence of these types as compared to those vaccinated (28.9% vs. 13.6%, respectively, p-value =.03). The unvaccinated women showed a lower prevalence for HPV types covered by the 9-valent vaccine compared to the vaccinated cohort (43.2% vs. 45.5%). However, this difference was not statistically significant. We found a high prevalence of anal HPV among these women, with lower prevalence of 4-valent and 2-valent HPV types among vaccinated women, evidencing the pivotal role of HPV vaccination. Future research should assess the 9-valent vaccine's long-term effectiveness against more HPV types. Funding: Research Centers in Minority Institutions (RCMI), University of Puerto Rico (NIMHD # 2U54MD007600-36), and CAPAC Research Training Program (NCI #R25CA240120). Citation Format: Anelisse Dominicci-Maura, Ana Patricia Ortiz, Josefina Romaguera, Filipa Godoy-Vitorino. Prevalence of anal HPV infection in women attending a gynecology and colposcopy clinic: Assessing the potential impact of HPV vaccination [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 4804.

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 7328: Relationship between PIN3 16bp duplication of TP53 and HPV in HIV women in Mali

Abstract Background: TP53 polymorphisms can influence the immune response to HPV, affecting TP53's role in cell cycle regulation and apoptosis, crucial for controlling HPV infection and preventing cancer. Objective: Explore the link between TP53 PIN3 16-bp duplication and HPV infection in HIV-positive Malian women. Methods: This study explored the link between PIN3 16-bp duplication polymorphism of TP53 and HPV infection in 50 HIV-positive women in Mali. Data included surveys, self-sampled vaginal swabs, and blood collection. HPV typing used GeneXpert, and PIN3 genotyping utilized AS-PCR. Results: Participants, primarily &amp;gt;30 years (92%), had a mean age of 43.30 ± 10.332 years. HPV prevalence was 36%, with P3 being the most common subtype (30.8%). PIN3 genotypic frequencies were A1A1 (50%), A1A2 (34%), and A2A2 (10%). History of sexually transmitted infections correlated with higher mutation rates (37.8% A1A2, 10.8% A2A2). A2A2 genotype prevalence was higher in HIV-positive women with specific HPV subtypes (P5, P4, HPV16, P3, P18/45). A1A2 genotype was observed in 60% of HPV subtype P3 cases and 20% of P4 and P18/45 cases. Conclusion: These results suggest a link between TP53 gene polymorphisms and susceptibility to different HPV subtypes in HIV-positive women, warranting further research into their functional implications and impact on HPV-related diseases in this population. Keywords: TP53 polymorphism, HPV, HIV, Malian population Citation Format: Mamoudou Maiga, Brehima Diakite, Yaya Kassogue, Ban Traore, Oumar Kassogue, Bakarou Kamate, Cheick B. Traore, Jane L. Holl, Lifang Hou. Relationship between PIN3 16bp duplication of TP53 and HPV in HIV women in Mali [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 7328.

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 5664: Genetic alterations and pharmacological response profiles from 10 cervical cancer cell lines

Abstract Background: There are significant parallels between CC cell lines (CCCL) and newly diagnosed tumors, the most prominent being HPV infection/integrations and PI3K as well as epigenetic pathway alterations. Objectives: Identify genomic alterations associated with resistance to specific drug families in pharmacological profiles in Cell Lines (CL) and in Primary Tumors. Material and Methods: 16 public and 4 newly patient-derived CL have been extensively characterized by HPV type, genetic (WES) and protein (RPPA) profiles. Pharmacological profiling against 32 drugs was carried out in triplicate samples and repeated on 10 selected CL. Variant calling of small-scale alterations (SNVs, InDels) was performed using GATK HaplotypeCaller (v4.0.2.1). Variants annotation was performed with Annovar (v 2017/07/06) using respectively gene (refGene), known polymorphims (avsnp v147, 1000G v2015/08, ESP6500v2, ExAC) and cancer databases (COSMIC v70, ICGC v21) as well as deleterious impact predictors (dbNSFP v33). Copy number alterations were assessed using Facets (v0.5.11) with 4 blood samples from the RAIDs tumor project used to generate a “baseline” copy number profiles for CLs. Results: All 10 cell lines had strikingly similar DSS (drug sensitivity scores) to a family of four different microtubule targeting agents (MTAs). Bioinformatics subtraction of genetic alterations present in resistant (CRL 10302, CRL 7920, CRL 1550) and absent in sensitive CLs: (IC1, IC3, IC5), revealed a consistent LoF (loss of function) alteration in one single gene: PABPC3 ‘Poly A tail binding protein, cytoplasmic C3’, a gene involved in messenger RNA stability and translational initiation. Additionally, 50 gene alterations from the pathway “POST TRANSLATIONAL MODIFICATIONS OF TUBULIN” were variably detected in resistant CLs. In primary tumors from the RAIDS database, alterations in PABPC3 were present in 10/301 (3%), half of which documented by at least one database: (Cosmic, ICGC, Cancer Hotspot). All CLs were sensitive to Bortezomib, Omipalisib and Palbociclib. A large spectrum activity to Vorinostat, (HDAC inhibitor) in line with frequent (sensitizing) LoF alterations in epigenetic suppressor genes, contrasted with a selective response to other well-known CC drugs: Methotrexate, Gemcitabine, Sorafenib. Three out of CL were highly sensitive to APR246 (Eprenetapopt) as single agent. Bioinformatics gene subtraction identified OSBPL1A, a marker of synthetic lethality in the ferroptosis pathway, in all three CLs. Discussion and Conclusion: A string of LoF alterations (CSMD2/CSMD3, ZNF717, CDC27) had been previously associated with poor response to radiation or to chemo-radiation, in tumors and are present in most CLs which are derived from resistant tumors. Future objectives are to validate the present biomarker findings in the context of a clinical platform trial. Citation Format: Suzy Scholl, Pierre Gestraud, Elodie Girard, Lolita Lecompte, Maral Halladjian, Leanne de Koning, Nicolas Servant, Maud Kamal, Elaine Del Nery. Genetic alterations and pharmacological response profiles from 10 cervical cancer cell lines [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 5664.

CLIA Validation of a New High Performance HPV ctDNA Assay Covering Multiple High Risk HPV Types

CLIA Validation of a New High Performance HPV ctDNA Assay Covering Multiple High Risk HPV Types

Vaccination against human papillomavirus in aggressive juvenile respiratory papillomatosis

In recent years there has been an increase in cases of papillomatosis of the upper respiratory tract, including in childhood, which is a significant problem. More than 70 % of children have severe recurrent forms of the disease. It has been proven that the development of respiratory papillomatosis is associated with infection with human papillomavirus, more often HPV types 6 and 11. The development of respiratory papillomatosis in childhood may be a consequence of infection with the human papillomavirus of the respiratory tract at the time of birth, and HPV reactivation may occur after injury or infection. The treatment of this condition is a significant problem, since during surgical treatment, only the visible pathological process is excised, and no effect on the etiological factor is produced. Therefore, the most optimal can be considered to be vaccination against HPV with available vaccines at the stage of pregnancy planning in previously unvaccinated individuals, as well as vaccination against HPV in already infected individuals with existing respiratory papillomatosis. In our article, we present a case of successful vaccination of a 2-year-old child with an aggressive course of respiratory papillomatosis against HPV.

Extended HPV typing test performed better predict value for CIN2+ among elderly women in China

ObjectiveThe aim of this study was to examine the cervical cancer screening practices among women residing in Lingang New District of Shanghai. Moreover, the study aimed to delve into the characteristics of HPV infection and cervical lesions in older women (≥60 years old), seeking for more effective method for cervical cancer screening. MethodsThis is a cross-sectional study enrolled women who were referred to colposcopy and cervical histological examination due to abnormal cytology or HPV tests from Shanghai Sixth People's Hospital between January 2018 and December 2022. ResultsA total of 1,931 women (mean age: 41.8 ± 12.5, range: 18–88 years old) were enrolled, 119 individuals aged ≥ 60 and 1732 aged <60. The infection rates of HPV52, 33, 35, 56, 26 and 81 were significantly higher in the elderly group. Multiple HPV infection rates were also higher in this group and were associated with cervical lesions. The probability of LSIL, HSIL and Ca in women over 60 years old was significantly higher compared to women under 60. The top three HPV genotypes in elderly women with CIN2+ were HPV16, 52, and 58. The Yoden index was higher for extended typing for HPV 31/33/45/52/58(0.41) compared to cytology(0.29), high risk HPV without specific typing(0.07), cotest(cytology and high risk HPV, 0.06 or 0.30), or the current shunt strategy(0.07). ConclusionsElderly women still need to continue cervical cancer screening, and extended typing test for HPV16/18/31/33/45/52/58 is a more effective method for this age group.

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.

(148) The Prevalence and Genotype Distribution of Human Papillomaviruses in Korean

Abstract Introduction Human papillomavirus (HPV) prevalence and genotype distribution are different between various nations and regions. Additionally, previous studies have mainly focused on HPV infection in western female and epidemiological studies of HPV infection in regional populations have been rarely reported. The lack of information on the HPV genotype distribution of the regional population in each individual country or region raises questions about the effectiveness of the current 9-valent vaccination. Objective To assess the prevalence and genotype of HPV(+) Korean and to know whether currently available 9-valent vaccine can cover the most prevalent and high risk genotype as HPV vaccine in Korean. Methods Between January 2014 to June 2022, samples of 44,065 men (Study I, M) and 564,499 females (Study II, F), who were volunteered for testing or recommended by a clinician, were tested for HPV detection and genotyping. Samples were collected swabs from the pap smear test. HPV detection and typing were conducted using the Anyplex™ II HPV 28 Detection system, which detects 19 high-risk (HR) HPVs and 9 low-risk (LR) HPVs. Results In Study I &amp; Study II, overall prevalence were 59.7% (M), 44.3%(F), prevalence of HR were 30.6%(M), 37.5%(F) and LR HPVs were 50.1%(M), 18.3%(F), respectively. Overall HPV prevalence was higher in teens (34.1% in M and 58.3% in F) and 20s (33.8% in M and 51.9% in F) with age [Table 1]. The most prevalent genotypes of HR were 16 (5.2%), 53 (4.6%), 51 (4.2%), 52 (3.8%), 58 (3.7%), 39(3.6%) and 66(3.4%) in Study I. In Study II of Female, the most prevalent genotypes of HR were 52 (7.1%), 53 (6.2%), 58 (5.0%), 68 (4.8%), and 16 (4.3%). In Study I of 26,299 men with HPV infection, 9,259 (35.2%) had a genotype with HR; 53 (4.6%), 51 (4.2%), 39(3.6%) and 66(3.4%), which could not prevented by the 9-valent vaccine. In Study II of 211,883 females with HPV infection, 72,252 (34.1%) had a genotype with HR, 68 (4.8%), 51 (4.1%), 39 (3.8%), and 56 (3.7%) which could not be prevented by the 9-valent vaccine. Conclusions In this study, Korea male and female aged under 30 years showed a high prevalence of HR HPVs. In both Male and Female groups, a significant number of HR HPVs infections were not prevented by 9-valent vaccine. Based on this result, it is necessary to develop nation-specific HPV vaccination for Korean. Further, this approach can be applied in other countries. Disclosure No.