HPV DNA Research Articles

Prevalence and genotype distribution of HPV infections among women in Chengdu,China

BackgroundHuman papilloma virus (HPV) infection among female is the cause of cervical cancer and genital warts. In China, the HPV vaccination rate and the target population screening rate among females are low, and the aims of this study on the genotype distribution and prevalence of HPV infection were to provide more targeted strategies for the prevention and treatment of cervical cancer and HPV-related diseases.MethodsPolymerase chain reaction-reverse dot blot (PCR-RDB) was adopted for HPV genotyping test, the prevalence and 23 genotypes distribution of HPV infections among 181,705 women in Chengdu from 2013 to 2020 were analysed.ResultsThe overall prevalence rate of HPV infection among 181,705 cases was 23.28%, the prevalence of HR-HPV at the age group < 20 years, 60–69 years and ≥ 70 years were higher than the overall prevalence.The prevalence of HPV showed a bimodal U-shaped curve with age; the first and second peak common occurred among females < 20 years old (42.97%) and 60–69 years old (37.56%), respectively.The top five genotypes of HPV infection among females in Chengdu were HPV52/16/58/81/53. Single infection (73.26%) was the main HPV infection pattern, followed by double infection (19.17%) and multiple infection (7.57%), the infection rate of HPV showed a gradual declined as the patterns of HPV coinfections increased, low-risk and high-risk coinfection was higher in low-risk HPV infection (43.68%) and lower in high-risk HPV infection (13.59%). The prevalence of genotypes − 6 and − 81 infection was the second highest at the age group of 20 and 40–59, respectively, while the prevalence of HPV16 was the highest at the age group of ≥ 70 among 23 genotypes among the 181,705 women.ConclusionsThe prevalence of HPV infections among women in Chengdu is higher than domestic certain developed citys, among the five vaccines available, nonavalent vaccine is more suitable for Chengdu females. For young females prioritizing vaccination is essential in the current context.Double screening for HPV DNA is important in middle-aged women (30–49 years), and screening should not be lacking in older women (> 65 years). Additionally,for patients with genital warts, it is necessary to screen for high-risk HPV infection and provide appropriate management and treatment. Given the limitations of this study, future HPV research should aim to achieve full coverage of the target population, and our studies should also include cellular or pathological data of HPV-positive cases, vaccination rates, and various lifestyle details.

Abstract 1637 Molecular mechanism of HPV DNA replication initiation, mediated by E1 and E2 proteins

Abstract 1637 Molecular mechanism of HPV DNA replication initiation, mediated by E1 and E2 proteins

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.

Concentration strategies for spiked and naturally present biomarkers in non-invasively collected first-void urine

BackgroundFirst-void urine (FVU) provides a non-invasive method for collecting a wide range of biomarkers found in genital tract secretions. To optimize biomarker collection in FVU, this study investigated the impact of naturally present and supplemented precipitating agents: uromodulin (UMOD) and polyethylene glycol (PEG), on the concentration of human papillomavirus (HPV) pseudovirions (PsV), cell-free DNA (cfDNA), and cellular genomic DNA (gDNA) through centrifugation.MethodsFVU samples from ten healthy female volunteers, along with a control sample, were spiked with seal herpesvirus 1 (PhHV-1) DNA, HPV16 plasmid DNA, and HPV16 PsV with an enhanced green fluorescent protein (EGFP) reporter. The samples were subjected to various concentration protocols involving PEG precipitation, low-speed centrifugation (5 min at 1000×g), and medium-speed centrifugation (1 h at 3000×g). Subsequently, quantitative PCR (qPCR) was used to assess cellular and cell-free glyceraldehyde-3-phosphate dehydrogenase (GAPDH) DNA, cell-free PhHV-1 and HPV16 DNA, and PsV (EGFP) DNA. In addition, UMOD levels were measured.ResultsThe findings revealed that PEG significantly increased the concentration of cfDNA and gDNA in the pellet after centrifugation, with the most pronounced effect observed for cfDNA. Moreover, low-speed centrifugation without PEG effectively depleted cellular gDNA while preserving cfDNA in the supernatants. Pseudovirions were consistently pelleted, even with low-speed centrifugation, and a positive but not significant effect of PEG on PsV (EGFP) DNA yield in the pellet was observed. Additionally, a significant correlation was observed between UMOD and GAPDH, HPV16, and PsV (EGFP) DNA quantities in the pellet. Furthermore, large variations among the FVU samples were observed.ConclusionsWith this study, we provide novel insights into how various biomarker precipitation protocols, including both the properties of FVU and the use of PEG as a precipitating agent, influence the concentration of cfDNA, cellular gDNA, and pseudovirions.

Association between Human Papillomavirus 16 Viral Load in Pregnancy and Preterm Birth.

Recent evidence shows increased preterm birth risk with human papillomavirus-16 (HPV16) infection during pregnancy. This study aimed to measure the association between HPV16 viral load during pregnancy and preterm birth. We used data from participants in the HERITAGE study. The Linear Array assay was used for HPV DNA testing on vaginal samples collected during the first and third trimesters of pregnancy. The HPV16 viral load was measured with a real-time polymerase chain reaction. We used logistic regression to measure the associations between HPV16 viral load during pregnancy and preterm birth (defined as birth before 37 weeks of gestation). The adjusted odd ratios (aORs) and the 95% confidence intervals [CIs] were estimated with inverse probability treatment weighting of the propensity score. This study included 48 participants who tested positive for HPV16 during the first trimester of pregnancy. The aOR for the association between first-trimester HPV16 viral load (higher viral load categorized with a cutoff of 0.5 copy/cell) was 13.04 [95% CI: 1.58-107.57]). Similar associations were found using different cutoffs for the categorization of viral load during the first and third trimesters. Our findings suggest a strong association between a high HPV16 viral load during pregnancy and preterm birth, demonstrating a biological gradient that reinforces the biological plausibility of a causal association.

Effects of 5-aminolevulinic acid photodynamic therapy for cervical low-grade squamous intraepithelial lesions with HR-HPV infections.

To determine the effectiveness and safety of 5-aminolevulinic acid mediated photodynamic therapy (5-ALA PDT) in HR-HPV infected patients with cervical low-grade squamous intraepithelial lesions (LSIL) and to explore possible factors affecting treatment outcomes. This retrospective study included 96 patients with histologically confirmed cervical LSIL and high-risk human papillomavirus (HR-HPV) infection. They received 5-ALA PDT treatment once a week for a total of 3 courses. All patients were evaluated by cytology tests, HPV DNA assay, colposcopy, and biopsy at 2 weeks, 3 months, and 6 months checkpoint. The chi-square test were used to evaluate the differences in various clinical data, and a p value <0.05 was considered statistically significant. At 2 weeks, 3 months, and 6 months checkpoint, colposcopies showed that the cervical iodine-unstained area under VILI (visual inspection with Lugol's iodine) significantly reduced (p < 0.01) with no structure changes. At 3 months and 6 months checkpoint, the pathological regression rate reached 87.5% (84/96) and 94.79% (91/96), while the HR-HPV clearance rates reached 80.21% (77/96) and 93.75% (90/96) respectively. We also examined the efficacy in the HPV 16/18-related group and non-HPV 16/18-related group. The HR-HPV clearance rate in the HPV16/18 group [94.87% (37/39)] was significantly higher than that of the non-HPV 16/18 group [70.17% (40/57)]. However, at 6 months after treatment, the clearance rate of the HPV 16/18 group [94.87% (37/39)] showed no statistical difference from the non-HPV 16/18 group [92.30% (53/57)]. Topical 5-ALA PDT can effectively eliminate HR-HPV infection and treat low-grade cervical squamous intraepithelial lesions, it offers an alternative treatment option for patients with LSIL, especially for those with fertility requirements and who wish to preserve cervical structure or function.

The role of cervical elastography in the differential diagnosis of preinvasive and invasive lesions of the cervix.

This study aims to evaluate the role of cervical elastography in the differential diagnosis of preinvasive and invasive lesions of the cervix. A total of 95 women participated in this prospective study and were divided into the following groups: 19 healthy subjects (group 1) with normal cervicovaginal smear (CVS) and negative human papillomavirus test (HPV DNA), 19 women with normal cervical biopsy and normal final pathological result of cervical biopsy (group 2), 19 women with low-grade squamous intraepithelial lesion (LSIL) (group 3), 19 women with high-grade squamous intraepithelial lesion (HSIL) (group 4), and 19 women with cervical cancer (group 5). Clinical, demographic, histopathological, and elastographic results were compared between these groups. Comparing groups, age (40.42 ± 8.31 vs. 39.53 ± 8.96 vs. 38.79 ± 9.53 vs. 40.74 ± 7.42 vs. 54.63 ± 12.93, p < 0.001 respectively), gravida (1.74 ± 1.33 vs. 2.16 ± 1.68 vs. 2.21 ± 1.96 vs. 2.53 ± 1.93 vs. 4.63 ± 2.17 p < 0.001 respectively), parity (1.37 ± 0.68 vs. 1.68 ± 1.20 vs. 1.58 ± 1.30 vs. 2.00 ± 1.67 vs. 3.37 ± 1.61, p < 0.001 respectively), and the proportion of patients at menopause (10.5% vs., 15.8% vs. 10.5% vs. 5.3% vs. 57.9%, p < 0.01 respectively), a statistically significant difference was found (Table1). However, no statistically significant difference was found in the number of abortions, BMI, mode of delivery, smoking, additional disease status, history of surgery, and family history (p > 0.05) (Table2. As a result of the applied roc analysis, mean cervical elastographic stiffness degree (ESD) was found to be an influential factor in predicting cervical cancer (p < 0.05). The mean cut-off value was 44.65%, with a sensitivity of 94.7% and a specificity of 96.1% (Table7). Measurement of ESD by elastography is a low-cost, easily applicable, and non-invasive indicator that can distinguish cervical cancer from normal cervical and preinvasive lesions. However, it is unsuitable for determining preinvasive cervical lesions from normal cervix.

Mediating Effect of White Blood Cells and Tobacco Exposure on Cervical Neoplasm Risk Among Taiwanese Women.

Background: Both the high-risk human papillomavirus (HR-HPV) infection and tobacco exposure are significantly associated with cervical neoplasm risk. Immune cells play important roles in carcinogenesis. However, it is still unclear whether immune cells have a mediating effect on the HR-HPV infection and tobacco exposure with cervical neoplasm development. Aim: The aim of this study was to determine how the increased white blood cell (WBC) count affects the relationship between HR-HPV DNA load and tobacco exposure in the development of cervical neoplasia. Methods: A hospital-based case-control study design was conducted with a total of 108 cases of Taiwanese women with ≥ cervical intraepithelial neoplasia (CIN) I confirmed by biopsy, and 222 healthy Taiwanese female subjects with negative findings on a Pap smear were assigned to the control group. The study evaluated HR-HPV status and immune cell counts (WBCs, natural killer (NK) cells) and tobacco exposure by a self-construct questionnaire. Results: Both HR-HPV DNA load and tobacco exposure significantly independently increased cervical neoplasm risk (AORs: 1.28 and 1.42, respectively). Similar significant results were found for WBCs and NK cells, with respective AORs of 1.20 and 1.00. Moreover, increased WBCs (β = 0.04, 95% CI corrected: 0.01-0.07) and tobacco exposure (β = 0.02, 95% CI corrected: 0.01-0.04) mediated the relationship between the high-risk HPV DNA load and cervical neoplasm risk. Conclusions: Elevated WBC count acts as both predictor and mediator in cervical neoplasm development linked to HR-HPV DNA load. Monitoring and maintaining WBC levels within the normal range could be a preventive strategy for cervical neoplasm development.

Development and validation of artificial intelligence-based analysis software to support screening system of cervical intraepithelial neoplasia

Cervical cancer, the fourth most common cancer among women worldwide, often proves fatal and stems from precursor lesions caused by high-risk human papillomavirus (HR-HPV) infection. Accurate and early diagnosis is crucial for effective treatment. Current screening methods, such as the Pap test, liquid-based cytology (LBC), visual inspection with acetic acid (VIA), and HPV DNA testing, have limitations, requiring confirmation through colposcopy. This study introduces CerviCARE AI, an artificial intelligence (AI) analysis software, to address colposcopy challenges. It automatically analyzes Tele-cervicography images, distinguishing between low-grade and high-grade lesions. In a multicenter retrospective study, CerviCARE AI achieved a remarkable sensitivity of 98% for high-risk groups (P2, P3, HSIL or higher, CIN2 or higher) and a specificity of 95.5%. These findings underscore CerviCARE AI's potential as a valuable diagnostic tool for highly accurate identification of cervical precancerous lesions. While further prospective research is needed to validate its clinical utility, this AI system holds promise for improving cervical cancer screening and lessening the burden of this deadly disease.

Clinical Characteristics of Basal Cell Carcinomas of the Scrotum: An Institutional Retrospective Review

Objective. To analyse the clinical and pathologic features, discuss therapeutic strategies, and possibly cause and identify prognostic factors of scrotal basal cell carcinoma (BCC) in Chinese patients. Materials and Methods. Between January 2012 and December 2022, 12 patients with scrotal BCC were diagnosed and treated at our institution. A review was conducted based on the clinical characteristics, pathology slides, and tissues of these patients. Results. The median patient age was 69.26 ± 11.23 years. The skin lesions presented as red papules, blue-grey polypoid nodules, erythematous patches, brownish plaques, and so on. All patients were treated using wide excision, but the margins varied from 0.5 cm to 2 cm. HPV infection was checked in all lesions, with 4 out of 12 testing positive for P16 and 1 for HPV16 DNA. We found mottled positive expression of P16 in the cytoplasm and membrane. One patient developed left inguinal lymph node metastasis and was successfully treated using bilateral inguinal lymphadenectomy. The rest recovered well without relapse. Conclusions. BCC of the scrotum is rare, but long-term surveillance is recommended for BCC patients, and whether genital HPV infection is a noteworthy feature for these patients remains under investigation.

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.

Clinical Performance of Self-collected Specimen HPV-DNA vs Clinician- collected Specimen HPV-mRNA to Detect High-risk HPV and High-grade Cervical Lesions and Cancer.

Self- collected specimens to detect high-risk (hr) HPV and high-grade cervical lesions (CIN2+) has been introduced aiming to increase cervical cancer screening coverage. The performance of self- collected specimen compared to clinician collected specimen is one major concern. This study aimed to compare self-sampling HPV-DNA and clinician-sampling HPV-mRNA to detect hr-HPV and high-grade cervical lesions. Women with abnormal cervical cytology and/ or positive hr-HPV who attended the colposcopy clinics in 10 tertiary hospitals in Bangkok were enrolled. Self-collected specimens were evaluated for HPV DNA using Cobas® 4800 HPV test prior to the clinician-collected specimens which were tested for HPV mRNA with APTIMA® HPV Assay. Subsequent colposcopy with biopsy was performed. The detection rates of hr-HPV from both HPV tests and their performance to detect high-grade lesions pathology were compared. Data from 497 women's specimens were analyzed. Both samplings had 86.8% concordance rate in detecting hr-HPV (Kappa 0.670; 95% confidence interval [CI] 0.599-0.746, P value < 0.001). The sensitivity (95% CI) of self-collected specimen HPV DNA and clinician- collected specimen HPV-mRNA to detect high-grade lesions were 91.8% (85.4%-96.0%) and 90.2% (83.6%-94.9%) respectively. The corresponding negative predictive values (95% CI) were 91.9% (85.6%-96.0%) and 91.7% (86.0%-95.7%) respectively. HPV DNA testing from self-collected specimen to detect HR-HPV demonstrates high concordance with HPV mRNA testing from clinician-collected specimen. The sensitivity and negative predictive value of both tests to detect high-grade lesions are comparable.

Detection of free DNA based on metal-enhanced fluorescence triggered by CRISPR-Cas12a and colorimetric analysis.

The CRISPR-Cas system has been found to be extremely sensitive and there is an urgent demand to extend its potential in bioassays. Herein, we developed a novel nanobiosensor to detect the human papillomavirus 16 genes (HPV-16 DNA), which is triggered by CRISPR-Cas12a to amplify the fluorescence signal by metal-enhanced fluorescence (CAMEF). Along with the changing of the fluorescence signal, the aggregation of the substrate of MEF also leads to a change in the color of the mixture solution, enabling dual signal detection with the fluorescence and the naked eye. Furthermore, the designed CAMEF probe was verified to detect the HPV-16 DNA accurately and reliably in biological samples. Triggered by the CRISPR system, the designed CAMEF probe allows quantitative detection of the HPV-16 DNA in the wide range of 10-500 pM. Owing to the MEF, the fluorescence signal of the CAMEF probe was significantly amplified with the detection limit as low as 1 pM. Besides, we can determine the concentration of HPV-16 DNA simply by the naked eye, which also drastically reduces the possibility of false-positive signals. Theoretically, the target ssDNA could be any strand of DNA obtained by designing the crRNA sequence in the CRISPR-Cas system. We believe that the designed CAMEF sensor can present a reliable approach for the accurate detection of low amounts of target ssDNA in complex biological samples.

Molecular Genetic Basis of Cervical Cancer

Background: Cervical cancer is a cancer that occurs in the cells of the cervix–the lower part of the uterus that connects it to the vagina and represents a global public health problem. In 2008, 530,000 new cases and 275,000 deaths from cervical cancer were recorded worldwide, and in 2018, an increase to 570,000 new cases and 311,000 deaths was recorded. For many years, it has been known that the main cause of preinvasive lesions and cervical cancer is the human papillomavirus–HPV. The total prevalence of HPV in the cervix in the general population of women is 10%. In developing countries, this prevalence is higher and describe most frequent clinical manifestations in the praxis. Objective: The aim of this study was to analyze and describe molecular genetic basis of cervical cancer and the most frequent clinical manifestations in the praxis. Methods: This is cross-sectional study based on meta-analysis of the facts published in scientific literature stored in indexed databases Medline, PubMed Central, Scopus, Hinari, etc., about molecular genetic basis of the cervical cancer with description of clinical manifestations and its consequences describing morbidity and mortality rate in the population worldwide. Results and Discussion: In 2008, 530,000 new cases and 275,000 deaths from cervical cancer were recorded worldwide, and in 2018, an increase to 570,000 new cases and 311,000 deaths was recorded. The main cause of preinvasive lesions and cervical cancer is the human papillomavirus–HPV. HPV infection is most common in young, sexually active women under the age of 25, but cervical cancer is more common in older women. Oncogenic types of human papillomavirus 16 and 18 together with HPV 45 and 31 are the causative agents of 80% of cervical cancer cases. HPV 16 has the highest oncogenic potential. Epigenetic changes include DNA methylation and post-translational modifications of histones, such as: methylation, acetylation, phosphorylation, ubiquitination and sumoylation. Cervical intraepithelial (CIN / SIL) lesion is a premalignant change of the cervix that occurs due to chronic infection with high-risk types of HPV. Persistent infection with oncogenic types of HPV causes almost all cases of cancer. HPV DNA was detected in 99.7% of cancer samples. Conclusion: There are four main steps in the development of cervical cancer: infection of the metaplastic epithelium of the transformation zone, viral persistence, progression towards precancerous lesions and invasion of the basement membrane. Histologically, in about 80% of cases, squamous cell carcinomas arise from preexisting dysplasias. Adenocarcinoma accounts for about 15-20% of cancer cases. HPV 16 is the main cause of squamous cell carcinoma, unlike HPV 18 which is typically associated with adenocarcinoma.

Cervical cancer screening and treatment costing in Senegal.

in Senegal, cervical cancer is the leading cause of cancers among women. This study estimated the costs associated with cervical cancer screening and treatment for precancerous lesions from the health system perspective. we estimated costs for screening, diagnostics, and treatment. We conducted a cross-sectional study in seven regions with primary data collected from 50 health facilities. Data collection included structured questionnaires, with secondary data from the Ministry of Health and other sources. A mixed-methods approach combined ingredients-based costing and financial expenditures to estimate direct medical and non-medical costs. All costs are reported in 2019 USD. average costs were $3.71 for visual inspection with acetic acid, $16.49 for Pap smear, and $46.65 for human papillomavirus deoxyribonucleic acid (HPV DNA) testing. Screening cost drivers were clinical exam supplies and clinical equipment for visual inspection with acetic acid, offsite processing of specimens for Pap smear, and lab equipment costs for HPV DNA procedure. The average cost of diagnosis via colposcopy alone was $25.73, and colposcopy with biopsy/endocervical curettage was $74.96. The average cost of treatment followed by one visit for pre-cancerous lesions was $195.24 for loop electrosurgical excision, $47.35 for cryotherapy, and $32.35 for thermal ablation. Clinical equipment and lab costs were the largest contributors to colposcopy and endocervical curettage/biopsy expenses. Clinical equipment made up the largest portion of cryotherapy, loop electrosurgical excision, and thermoablation costs. this study is the first to estimate the costs of HPV screening and treatment in Senegal, which can be used to inform decision-making on cervical cancer investments.

Herpesviruses and human papillomaviruses in saliva and biopsies of patients with orofacial tumors

ObjectivesTo determine the prevalence and association of HPV and Herpesviruses in saliva and tissue samples of patients with orofacial tumors. MethodsBiopsies of tumors were done, and saliva samples were collected from patients with orofacial tumors for the determination of viruses using nested multiplex PCR. Independent variables were sex, age, comorbidities, tumor stage, and length of stay. Outcome variables were the presence or absence of herpesviruses and HPV. Descriptive summaries and inferential statistics were done. ResultsA hundred patients were included in the study. Prevalence of herpesviruses and HPV were 17.6 % and 57.0 % in tumors, and 48.3 % and 60.0 % in the saliva of patients respectively. Herpesviruses detected included EBV (21.3 %), HHV-7 (11.2 %), CMV (6.7 %), HSV-1 (5.1 %), HSV-2 (1.1 %), VZV (1.1 %), and Kaposi sarcoma virus (0.6 %). The most prevalent HPV genotypes were HPV-42 (29 %), HPV-43 (22.7 %), HPV-52 (22.2 %), HPV-39 (18.8 %), and HPV-18 (9.1 %). The odds of EBV being detected in malignant orofacial tumors were 2 times that of benign orofacial tumors. HPV DNA in the saliva of patients with orofacial tumors was 69.7 %, compared to 18.2 % of the control sample (p < 0.001). The median length of stay for all participants was 6.5 days, those associated with viruses stayed longer. ConclusionThere was a high prevalence of Herpesviruses and HPV in saliva and tumor samples of patients with orofacial tumors, signalling some potential for more work to be done in this area.

Rapid immunoassay for dual-mode detection of HPV16 and HPV18 DNA based on Au@PdPt nanoparticles.

Cervical cancer (CC) remains one of the most severe global health challenges affecting women, primarily due to persistent infection with high-risk human papillomavirus (HPV) subtypes, particularly with HPV16 and HPV 18. Effective detection of these high-risk HPV strains is crucial for CC prevention. Current screening programs for HPV DNA include PCR and in situ hybridization, which are accurate and sensitive. However, these approaches demand a high level of expertise, along with expensive instruments and consumables, thus hindering their widespread use. Therefore, there is a compelling demand to develop an efficient, straightforward, and cost-effective method. Herein, we propose a lateral flow immunoassay (LFIA) method based on Au@PdPt nanoparticles for the simultaneous detection and genotyping of HPV16 and HPV18 within 15 min. This innovative approach allows for qualitative assessment by the naked eye and enables semi-quantitative detection through a smartphone. In this study, under optimal conditions, the qualitative visual limits of detection (vLOD) for HPV16 and HPV18 reached 0.007 nM and 0.01 nM, respectively, which were 32-fold and 20-fold more sensitive than conventional AuNPs-LFIA for HPV16 and HPV18, respectively. Meanwhile, semi-quantitative limits of detection (qLOD) for HPV16 and HPV18 were 0.05 nM and 0.02 nM, respectively. In conclusion, our formulated approach represents a significant step forward in HPV detection and genotyping, with the potential to enhance accessibility and effectiveness in the early diagnosis of CC at the point of care and beyond.

Liquid-based Cytology as a Superior Tool Compared to Conventional Pap Smear in Detecting Cervical Cancer in Suspected Cases: A Comparative Study

Abstract Introduction: Screening programs has conventional cytology such as Conventional Pap Smear (CPS) have successfully reduced cervical cancer, but newer tests like Manual Liquid-based cytology (MLBC) and Human Papillomavirus testing might enhance screening. Materials and Methods: This was a cross sectional study conducted on 175 samples was processed for CPS and MLBC. Cytobrush was used for LBC which was suspended and detached in the preservative fluid and processed by manual method. Histopathological correlation and HPV DNA testing was also done. Results: MLBC showed higher specimen adequately, cellularity, clean background and uniform distribution of cells than CPS. Conclusion: MLBC showed improved specimen adequately, better cytomorphological features and higher detection of epithelial cell abnormality.

Diagnostic Performance of p16ink4a in the Presence of E6/E7 mRNA in Formalin-fixed Paraffin Embedded Specimens: A Cross-sectional Study

Introduction: Clinically significant High-risk Human Papillomavirus (HR-HPV) infection in Oral Cavity Squamous Cell Carcinoma (OCSCC) is not clearly defined. There is uncertainty regarding the true impact of HPV-related variability (ranging from 0% to 100%) when using the GP5+/GP6+/MY09/11 (L1) primer. The identification of HPV DNA in tumours is insufficient to establish a causal viral association; therefore, a gold standard test is required to determine HPV’s role in malignant cells by identifying the transcripts of the E6/E7 mRNA viral oncogene and the p16ink4a biomarker. Aim: To assess the diagnostic performance of p16ink4a in the presence of E6/E7 mRNA in Formalin-fixed, Paraffin-embedded (FFPE) specimens. Materials and Methods: This cross-sectional study was conducted in the Department of Pathology at JIPMER in Puducherry, India, from February 2019 to April 2022. Combined molecular markers p16ink4a and E6/E7 mRNA (considered the gold standard) from FFPE specimens of newly diagnosed Squamous Cell Carcinoma (SCC) were analysed to identify biologically and clinically relevant Infections using Immunohistochemistry (IHC) and real-time Polymerase Chain Reaction (PCR). Results: This study indicates that tissue samples with p16 positive expression (score of 2 or higher) showed the presence of HPV E6/E7 mRNA, with a sensitivity of 100% and a specificity of 91.67%. The relationship between p16ink4a and E6/E7 mRNA expression in all OCSCC cases was found to be significant (p-value=0.003). Conclusion: The study found a significant relationship between mRNA and p16ink4a overexpression in tongue SCC. This finding suggests that alterations in mRNA expression levels are associated with changes in p16ink4a expression in tongue cancer. Such understanding could potentially aid in the development of diagnostic or therapeutic strategies targeting these molecular pathways in tongue SCC.