High-risk Human Papillomavirus DNA Research Articles

The association between smoking and cervical human papillomavirus infection among women from indigenous communities in western Botswana

Introduction Cervical cancer, a malignancy caused by infection with oncogenic human papillomavirus, disproportionally affects women from low resource settings. Persistence of human papillomavirus infection may mediate an association between tobacco use and cervical cancer. In limited resource settings, women from indigenous communities are often marginalized and do not benefit from evidence-based interventions to prevent tobacco use or cervical cancer due to the limited reach of mainstream healthcare services to these communities. This study determined the association between smoking and high-risk human papillomavirus infection among women from indigenous communities in western Botswana. Methods A cross-sectional study of women in indigenous communities was conducted between June and October 2022. Demographic, clinical and self-reported smoking data were collected. Cervical cytology and HPV DNA testing for high-risk human papillomavirus genotypes were performed. Multilevel multivariable logistic regression models were fit to evaluate the association between smoking and high-risk human papillomavirus infection while adjusting for potential confounders. Results A total of 171 participants with a median (interquartile range) age of 40 (31–50) years from three settlements and two villages were recruited for the study. Of these, 17% were current smokers, 32.8% were living with HIV and high-risk human papillomavirus DNA was detected in 32.8% of the cervical specimens. Women who were current smokers, were nearly twice as likely to have cervical high-risk human papillomavirus infection compared to non-smokers (Adjusted Odds Ratio (95% CI); 1.74(1.09, 2.79)) after controlling for confounders. Conclusion These data underscore the need for effective tobacco control to help mitigate cervical cancer risk in this setting. These findings can help inform decisions about targeted cervical cancer prevention and tobacco cessation interventions for women from indigenous communities.

Relationship between P16INK4a Overexpression in Human Papillomavirus Infection in High Grade CIN and Cervical Carcinoma

Background: High-risk HPV strains are a well-known contributor to the carcinogenesis of cervical squamous cell carcinoma (SCC). Indeed, there has been a high detection of HPV DNA in SCC and precancerous lesions. Objective: The aim of the study was to assess the Relationship Between Human Papillomavirus Infection and P16INK4a Overexpression in Cervical Squamous Cell Carcinoma. Methodology: This descriptive cross-sectional study was carried out in the Pathology Department of DMC with collaboration of Bangabandhu Sreikh Mujib Medical University (BSMMU), Microbiology Department and Bangladesh Agricultural University (BAU), Mymansingh, during July 2017 to June 2018. A total 50 VIA positive and clinically suspected premalignant and malignant patient’s attendant at DMC included as study population. Colposcopic biopsy specimens were sent to the Department of Pathology, DMCH, for histopathological examination. Some portion of biopsy samples were preserved at -4ºC for HR-HPV DNA detection. Statistical analyses were done by using the SPSS 26.0. Result: Highest number of cases 20 (40%) were in fourth decade and their mean age was found to be 44.20±11.20, ranging from 28 to 67 years. Among 50 positive cases, maximum number of 32 (62%) cases were married between 16 to 20 years of age, 12 (22%) cases were married in less than 15 years of age and 6 (8%) cases were married at more than 20 years of age. The findings of colposcopic examinations of total 50 cases. Common diagnoses were CIN II in 24 (48%) cases, 8(16%) case represented CIN III, Squamous cell carcinoma in 16 (32%) cases and Adeno Carcinoma 2(4%) cases. In comparison of p16 score with cervical lesions in study subjects there were 26 true positive cases and 13 true negative cases. According to p16 score a total 37 (26 true positive+ 11 false positive) cases were p16 positive. Out of which 16(32.0%) and 21(42.0%) were HR-HPV positive and negative respectively. Similarly according to p16 score 13 nevative cases ........

A multicenter study on the accuracy of PAX1/JAM3 dual genes methylation testing for screening cervical cancer

Objective: To explore the value of cervical cytologic DNA methylation for screening cervical cancer. Methods: This study was a prospective multicenter study conducted from May to October 2022 in Peking Union Medical College Hospital, Zhejiang Provincial People's Hospital, and the Second Affiliated Hospital of Zhejiang University School of Medicine. Women who accepted opportunistic cervical cancer screening in gynecological outpatient clinics were subjected to liquid-based thin-layer cytology testing (TCT), high-risk human papillomavirus (hrHPV) DNA testing and PAX1/JAM3 dual-genes methylation testing (PAX1m/JAM3m). Colposcopy evaluation and biopsy were offered to women according to current guidelines. The accuracies of various testing methods and their combinations were compared based on histological diagnosis. Results: A total of 1 184 samples diagnosed by histopathology were included in this study, consisting of 541 cases (45.7%) of benign cervical tissue or chronic cervicitis, 273 (23.1%) of cervical intraepithelial neoplasia (CIN) 1, 168 (14.2%) of CIN2, 140 (11.8%) of CIN3, and 62 (5.2%) of cervical cancer. The sensitivity and specificity of PAX1m/JAM3m testing for detecting CIN2 or more severe lesions (CIN2+) were 74.1% and 95.9%, respectively. The sensitivity and specificity of PAX1m/JAM3m testing for detecting CIN3+were 87.6% and 86.8%, respectively. Receiver operating characteristic curve analysis showed that, for detecting CIN3+, the area under curve of PAX1m/JAM3m testing (0.872, 95%CI: 0.847-0.897) was significantly superior to TCT testing (0.580, 95%CI: 0.551-0.610) or hrHPV testing (0.503, 95%CI: 0.479-0.515) (all P values<0.05). Conclusions: The PAX1m/JAM3m test in cervical exfoliated cells has excellent accuracy for the diagnosis of both CIN2+and CIN3+, which is superior to traditional screening protocols and screening strategies.

Patient preference and acceptability of self-sampling for cervical screening in colposcopy clinic attenders: A cross-sectional semi-structured survey.

Low vaginal self-sampling has been pioneered as an important development to improve uptake of cervical screening globally. Limited research is available in specific patient groups in the UK exploring views around self-sampling to detect high-risk human papillomavirus (hrHPV) DNA. Therefore, we explored patient views to support development of a novel point-of-care self-sampling cervical cancer screening device, by undertaking a cross-sectional semi-structured questionnaire survey to explore preferences, acceptability, barriers and facilitators around self-sampling. Patients attending a colposcopy clinic, 25-64 years old, were invited to participate after having carried out a low vaginal self-sample using a regular flocked swab. Participants self-completed an anonymous 12-point questionnaire. Quantitative data were analysed in MS Excel and Graphpad Prism, and qualitative data with Nvivo. We recruited 274 patients with a questionnaire response rate of 76%. Acceptability of self-sampling was high (95%, n = 187/197; Cronbachs-α = 0.778). Participants were asked their choice of future screening method: a) low vaginal self-sampling, b) healthcare professional collected vaginal swab, c) cervical brush sample with healthcare professional speculum examination, or d) no preference. Preferences were: a) 37% (n = 74/198), b) 19% (n = 37/198); c) 9% (n = 17/198), and d) 35% (n = 70/198), showing no single option as a strong preference. Key motivators were: Test simplicity (90%, n = 170/190), speed (81%, n = 153/190) and less pain (65%, n = 123/190). Barriers included lack of confidence taking the sample (53%, n = 10/19), resulting in preference for a healthcare professional sample (47%, n = 9/19). Whilst self-sampling showed high acceptability, lack of strong preference for screening method may reflect that respondents attending colposcopy are already engaged with screening and have differing perception of cervical cancer risk. This group appear less likely to 'switch' to self-sampling, and it may be better targeted within primary and community care, focusing on under-screened populations. Any shift in this paradigm in the UK requires comprehensive education and support for patients and providers.

High-Risk HPV CISH Detection in Cervical Biopsies with Weak and/or Focal p16 Immunohistochemical Positivity.

In cervical biopsies, for diagnosis of Human Papilloma Virus (HPV) related conditions, the immunohistochemical staining for p16 has a diagnostic value only if diffusely and strongly positive, pattern named "block-like". "Weak and/or focal (w/f) p16 expression" is commonly considered nonspecific. In our previous study, we demonstrated the presence of high-risk HPV (hrHPV) DNA by LiPa method in biopsies showing w/f p16 positivity. The aim of the present study was to investigate the presence of hrHPV-DNA by CISH in the areas showing w/f p16 expression. We assessed the presence of hrHPV16, 18, 31, 33, 51 by CISH in a group of 20 cervical biopsies showing w/f p16 expression, some with increased Ki67, and in 10 cases of block-like expression, employed as control. The immunohistochemical p16 expression was also assessed by digital pathology. hrHPV-CISH nuclear positivity was encountered in 12/20 cases of w/f p16 expression (60%). Different patterns of nuclear positivity were identified, classified as punctate, diffuse and mixed, with different epithelial distributions. Our results, albeit in a limited casuistry, show the presence of HPV in an integrated status highlighted by CISH in w/f p16 positive cases. This could suggest the necessity of a careful follow-up of the patients with "weak" and/or "focal" immunohistochemical patterns of p16, mainly in cases of increased Ki67 cell proliferation index, supplemented with molecular biology examinations.

The performance of single and combination test strategies using visual inspection, cytology, high-risk HPV DNA and HPV16/18 to screen South African women with and without HIV-infection

BackgroundCervical cancer screening strategies should ideally be informed by population-specific data. Strategies recommended for secondary prevention, are often inadequately studied in populations with high cervical disease burdens. This report describes the test performance measured against CIN2 + /CIN3 + histology in HIV-positive women (HPW) and HIV-negative women (HNW) with the aim to determine the most effective strategies to identify South African women at risk.MethodsPrimary screening using visual inspection, cytology and HPV DNA (cobas®) was performed in two South African provinces on 456 HPW and 639 HNW participating in the multicentric DiaVACCS trial. Histology was obtained for 91.7% screen-positive and 42.7% screen-negative participants, and unavailable histology was determined by multiple imputation to adjust for verification bias. Cross-sectional test performance was calculated for single and combination test strategies with and without intermediate risk categories using different cut-offs. Minimum acceptability for sensitivity and specificity, treatment and follow-up numbers were considered to evaluate strategies.ResultsThe only single test to reach acceptability in HPW was cytology (LSIL) [sensitivity 71.2%; specificity 90.5%; treatment 33.4%]; in HNW only HPV (hr) qualified [sensitivity 68.2%; specificity 85.2%; treatment 23.5%]. The universally best performing strategy which also resulted in smaller treatment numbers without intermediate risk group was primary HPV(hr), with treatment of both HPV(16/18) and cytology (ASCUS +) [HPW: sensitivity 73.6%; specificity 89.7%; treatment 34.7%. HNW: sensitivity 59.1%; specificity 93.6%; treatment 13.9%].DNA testing for hrHPV (any) and hrHPV (16/18) was the best universally acceptable strategy with an intermediate risk category (early follow-up) in HPW [sensitivity 82.1%; specificity 96.4%; treatment 17.1%; follow-up 31.4%] and HNW [sensitivity 68.2%; specificity 96.7%; treatment 7.6%; follow-up 15.9%]. In comparison, using both HPV (16/18) and cytology (ASCUS +) as secondary tests in hrHPV positive women, decreased follow-up [HPW 13.8%, HNW 9.6%], but increased treatment [HPW 34.7%, HNW 13.9%].ConclusionUsing hrHPV (any) as primary and both HPV16/18 and cytology as secondary tests, was universally acceptable without an intermediate risk group. Strategies with follow-up groups improved screening performance with smaller treatment numbers, but with effective management of the intermediate risk group as prerequisite.

An Evaluation of High-Risk HPV in Squamous Cell Carcinomas of the Lip in a South African Cohort

BackgroundTo determine the prevalence of HR-HPV in a series of lip SCC from South African patients, using currently accepted HPV-testing methodologies and to define the clinical and histomorphologic features of HPV-associated lip SCC.MethodsFifty SCC of lip and 50 control cases were tested for HR-HPV using p16 and HR-HPV DNA PCR. p16-equivocal/positive and HPV DNA PCR-positive SCC were further evaluated for the expression of HPV-16 and HPV-18 mRNA transcripts using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) to confirm transcriptionally active HPV.Resultsp16 was positive in 22% (n = 11) and equivocal in 4% (n = 2) of the SCC. One p16-positive case showed positivity for both HPV-16 DNA and HPV-16 E6/E7 mRNA transcripts (HPV prevalence rate of 2%). The HPV-positive case was non-keratinizing and occurred in an 80-year-old female. The two p16-equivocal cases were HR-HPV DNA positive and mRNA PCR negative. p16 was found to have a positive predictive value of 9%.ConclusionFindings from our cohort of lip SCC suggest that HR-HPV may have an insignificant role in the pathogenesis of SCC at this site. Due to its low ppv, p16 is insufficient to establish HR-HPV infection in SCC of the lip. The combination of p16 and DNA PCR appears to correlate with the presence of transcriptionally active virus. HPV E6/E7 mRNA detection is the gold standard for identifying HR-HPV. mRNA testing is not widely available in sub-Saharan Africa due to technical and financial constraints; however, the test appears to be of great value in p16-equivocal lip SCC.

Prevalence of high-risk human papillomavirus infection among women with diabetes mellitus in Accra, Ghana

BackgroundThere is increasing evidence of a higher risk and poorer prognosis of cervical cancer among women with diabetes mellitus (DM) compared to the general population. These are mediated by higher susceptibility to persistent high-risk human papillomavirus (hr-HPV) infection due to dysfunctional clearance in an immunocompromised state. We aimed to determine the prevalence of hr-HPV infection and cervical lesions in a cohort of women with DM in Ghana. We further disaggregated the prevalence according to DM type and explored factors associated with hr-HPV infection.MethodsThis retrospective descriptive cross-sectional study assessed 198 women with DM who underwent cervical screening via concurrent hr-HPV DNA testing and visual inspection with acetic acid in an outpatient department of the National Diabetes Management and Research Centre in Korle-Bu Teaching Hospital, Accra from March to May 2022. Univariate and multivariable binary logistic regression were used to explore factors associated with hr-HPV positivity.ResultsAmong 198 women with DM (mean age, 60.2 ± 12.1 years), the overall hr-HPV prevalence rate was 21.7% (95% CI, 16.1–28.1), disaggregated as 1.5% (95% CI, 0.3–4.4) each for HPV16 and HPV18 and 20.7% (95% CI, 15.3–27.0) for other HPV genotype(s). Respective hr-HPV prevalence rates were 37.5% (95% CI, 15.2–64.6) for type 1 DM, 19.8% (95% CI, 13.9–26.7) for type 2 DM, and 25.0% (95% CI, 8.7–49.1) for unspecified/other DM types. Past use of the combined contraceptive pill independently increased the risk of hr-HPV infection by approximately three times (adjusted odds ratio [aOR] = 2.98; 95% CI, 1.03 − 8.64; p-value = 0.045), whereas each unit increase in FBG level increased the odds of hr-HPV infection by about 15% (aOR = 1.15; 95% CI, 1.02 − 1.30; p-value = 0.021).ConclusionOur study points to a high prevalence of hr-HPV among women with DM and highlights a need for glycemic control among them as this could contribute to lowering their odds of hr-HPV infection. The low overall rates of HPV vaccination and prior screening also indicate a need to build capacity and expand the scope of education and services offered to women with DM as regards cervical precancer screening.

Comparing Cervical Cancer Screening Strategies in an Incarcerated Population.

Objective: To describe the prevalence of cervical intraepithelial neoplasia (CIN), high-risk human papillomavirus (hrHPV) infection, and cervical cancer in a high-risk, underscreened incarcerated population and to evaluate the performance of current cervical cancer screening options to detect cervical precancer (CIN 2/3) in this population. Study Design: Deidentified data were obtained from all cytological, hrHPV DNA, and histopathological testing of cervical biopsies performed on people incarcerated at the North Carolina Correctional Institute for Women between January 1, 2013, and December 31, 2020. These were linked to corresponding demographic data. The proportions of histopathological diagnoses of CIN2+ and CIN3+ immediately preceded by abnormal cytology testing or hrHPV testing were determined, and prevalence differences and 95% confidence intervals were calculated. Results: A total of 15,319 individuals incarcerated at the North Carolina Correctional Institute for Women had at least one cytology result during 2013-2020. Of these, 2,829 (18%) had abnormal cervical cytology, and 3,724 (24.3%) had positive hrHPV testing. The detection of CIN2+ was 95.9% by preceding abnormal cervical cytology, 89.9% by preceding positive hrHPV testing (p = 0.03), and 96.5% by preceding positive co-testing. The detection rate of CIN3+ was 96.6% by preceding abnormal cervical cytology, 90.8% by preceding positive hrHPV testing (p = 0.12), and 96.6% by positive co-testing. Conclusion: In our sample, primary cytology and co-testing detected CIN2+ at higher rates when compared with primary hrHPV testing. This reinforces that incarcerated populations do not fall into average-risk populations for which current cervical cancer screening options are designed, which should be considered when performing screening in this population.

Targeted therapies for HPV-associated cervical cancer: Harnessing the potential of exosome-based chipsets in combating leukemia and HPV-mediated cervical cancer.

Exosomes play a crucial role in intercellular communication and have emerged as significant vehicles for transporting disease-specific biomarkers. This feature provides profound insights into the progression of diseases and the responses of patients to treatments. For example, in leukemia, exosomes convey critical information through the carriage of specific proteins and nucleic acids. In the case of human papillomavirus (HPV)-mediated cervical cancer, exosomes are particularly useful for noninvasive detection as they transport high-risk HPV DNA and specific biomolecules, which can be indicators of the disease. Despite their vast potential, there are several challenges associated with the use of exosomes in medical diagnostics. These include their inherent heterogeneity, the need for enhanced sensitivity in detection methods, the establishment of standardization protocols, and the requirement for cost-effective scalability in their application. Addressing these challenges is crucial for the effective implementation of exosome-based diagnostics. Future research and development are geared towards overcoming these obstacles. Efforts are concentrated on refining the processes of biomarker discovery, establishing comprehensive regulatory frameworks, developing convenient point-of-care devices, exploring methods for multimodal detection, and conducting extensive clinical trials. The ultimate goal of these efforts is to inaugurate a new era of precision diagnostics within healthcare. This would significantly improve patient outcomes and reduce the burden of diseases such as leukemia and HPV-mediated cervical cancer. The integration of exosomes with cutting-edge technology holds the promise of significantly reinforcing the foundations of healthcare, leading to enhanced diagnostic accuracy, better disease monitoring, and more personalized therapeutic approaches.

Epidemiology of human papillomavirus infection in women from Xiamen, China, 2013 to 2023.

Cervical cancer is primarily caused by HPV infection. The epidemiology of HPV infection in specific areas is of great meaning of guide cervical cancer screening and formulating HPV vaccination strategies. Here, we evaluated the epidemiological characteristics of HPV infection in Xiamen population. In total, 159,049 cervical exfoliated cell samples collected from female outpatients in Women and Children's Hospital, School of Medicine, Xiamen between January 2013 and July 2023 were analyzed. HPV DNA detection was performed using HPV genotyping kits (Hybribio Limited Corp, China). An analysis was conducted on the prevalence of HPV infection, taking into account factors such as age, year, and multiple patterns of HPV infection. The differences in prevalence among age groups and years were compared using χ2 test. The overall prevalence of any 21 HPV genotypes was 18.4%, of which the high-risk HPV (HR-HPV) positive rate was 14.6%. The age-specific prevalence of HPV infection showed a bimodal distribution, with two distinct peaks, one at <25 years (31.2%) and the other at 60-64 years (32.9%). There was a downward trend in the prevalence of HPV infection over time, decreasing from 26.2% in 2013 to 14.5% in 2021, and then increasing to 19.0% in 2023. The five most prevent HR-HPV genotypes were HPV52 (4.0%), 58 (2.6%), 16 (2.5%), 51 (1.8%), and 39 (1.7%). Among the positive cases, 76.7% were detected with only one genotype and 23.3% with multiple genotypes. The most common co-infection was HPV52 + HPV58 (0.24%), followed by HPV16 + HPV52 (0.24%), HPV52 + HPV53 (0.21%), HPV52 + HPV81 (0.21%), HPV51 + HPV52 (0.19%), HPV16 + HPV58 (0.18%), and HPV39 + HPV52 (0.17%). The study provided the largest scale information on the recent epidemiological characteristics of HPV infection in Xiamen, and even in Fujian Province, China, which would support making the prevention and control strategies for cervical cancer in the region.

Multiple high-risk HPV infections probably associated with a higher risk of low-grade cytological abnormalities but not with high-grade intraepithelial lesions of the cervix

BackgroundFor women diagnosed with HR-HPV DNA positivity in community hospitals, the necessity of investigating the potential presence of multiple HR-HPV infections upon referral to tertiary medical institutions remains unclear.MethodsIn our cohort, women tested positive for HR-HPV DNA during examinations in community hospitals, were subsequently referred to tertiary medical facilities, reevaluated HR-HPV genotype and categorized based on cytological and histopathological results. The risk of cytologic/histopathology abnormalities and ≧ high grade squamous intraepithelial lesion(HSIL) or Cervical Intraepithelial Neoplasia (CIN) 2 associated with individual genotypes and related multiple HPV infections are calculated.ResultsA total of 1677 women aged between 21 and 77 were finally included in the present study. The cytology group included 1202 women and the histopathological group included 475 women with at least one HR-HPV infection of any genotype. We only observed a higher risk of low grade cytological abnormalities in women with multiple infections than those in corresponding single infections (for all population with an OR of 1.85[1.39–2.46]; p < 0.05). However, this phenomenon was not observed in histopathology abnormalities (CIN1). The risk of developing of ≥ HSIL/CIN2 in women who were infected with multiple HR-HPV also showed a similar profile to those with a single HR-HPV genotype.ConclusionMultiple HR-HPV infections is only associated with a higher associated risk of low grade cytological abnormalities. There is no evidence of clinical benefit to identify the possible presence of multiple HR-HPV infection frequently in a short period of time for women with HR-HPV-DNA positive.

Prevalence of high-risk human papillomavirus infection and cervical lesions among female migrant head porters (kayayei) in Accra, Ghana: a pilot cross-sectional study

BackgroundLittle attention has been given to the risk of high-risk human papillomavirus (hr-HPV) infection and cervical precancerous lesions among female migrant head porters (kayayei) in Ghana, as a vulnerable group, and to promote cervical screening in these women. This pilot study aimed to determine the prevalence of hr-HPV infection and cervical lesions among kayayei in Accra, the capital of the Greater Accra Region of Ghana and to describe our approach to triaging and treating these women.MethodsThis descriptive cross-sectional cohort study involved the screening of 63 kayayei aged ≥ 18 years at the Tema Station and Agbogbloshie markets in March 2022 and May 2022. Concurrent hr-HPV DNA testing (with the MA-6000 platform) and visual inspection with acetic acid (VIA) was performed. We present prevalence estimates for hr-HPV DNA positivity and VIA ‘positivity’ as rates, together with their 95% confidence intervals (CIs). We performed univariate and multivariable nominal logistic regression to explore factors associated with hr-HPV infection.ResultsGross vulvovaginal inspection revealed vulval warts in 3 (5.0%) and vaginal warts in 2 (3.3%) women. Overall, the rate of hr-HPV positivity was 33.3% (95% CI, 21.7–46.7), whereas the VIA ‘positivity’ rate was 8.3% (95% CI, 2.8–18.4). In the univariate logistic regression analysis, none of the sociodemographic and clinical variables assessed, including age, number of prior pregnancies, parity, past contraceptive use, or the presence of abnormal vaginal discharge showed statistically significant association with hr-HPV positivity. After controlling for age and past contraceptive use, only having fewer than two prior pregnancies (compared to having ≥ 2) was independently associated with reduced odds of hr-HPV infection (adjusted odds ratio, 0.11; 95% CI, 0.02–0.69).ConclusionIn this relatively young cohort with a high hr-HPV positivity rate of 33.3% and 8.3% of women showing cervical lesions on visual inspection, we posit that kayayei may have an increased risk of developing cervical cancer if their accessibility to cervical precancer screening services is not increased.

Human Papillomavirus-Attributable Head and Neck Cancers in India-A Systematic Review and Meta-Analysis.

Head and neck cancer accounts for about one third of the global burden in India. Mucosal high-risk human papillomavirus (HPV) has been hypothesized as a contributory risk factor for head and neck cancer (HNC) but its prevalence in Indian patients is not well established. Therefore, this systematic review and meta-analysis aimed to estimate the prevalence of HPV in HNC in India and their attributable fraction by considering the biomarkers of carcinogenesis, p16, and HPV E6/E7 mRNA. A systematic literature search was done in Medline via PubMed, Embase, Scopus, ScienceDirect, ProQuest, and Cochrane to identify studies on HPV and HNC in the Indian population, published between January 1990 and October 2022. Fifty-four eligible studies were identified and relevant clinical information was collected. Meta-analysis was conducted to estimate the pooled prevalence of HPV DNA, p16INK4a, and E6/E7 mRNA percent positivity by random-effect logistic regression model using Metapreg, STATA 18. Thirty-four high-quality studies were taken for meta-analysis. The pooled prevalence of HPV in HNC was 20% (95% CI, 12 to 32) with a high level of heterogeneity (I2 = 90.79%). The proportion of HPV in oropharyngeal cancer (OPC; 22% [95% CI, 13 to 34]) and laryngeal cancer (LC; 29% [95% CI, 17 to 46]) was higher than in oral cancer (OC; 16% [95% CI, 8 to 30]). The HPV-attributable fraction of OPC, considering the E6/E7 mRNA and p16 positivity, was 12.54% and 9.68%, respectively, almost similar to LC (11.6% and 9.57%), while it was much lower in OC (3.36% and 4%). The HPV-attributable fraction is considerably lower for OC, suggesting a negligible causative role of HPV in OC. A significant proportion of OPC and LC are attributed to HPV; however, their exact causative role is unclear because of the presence of other known risk factors.

HPV and p16 expression association with 5-year survival in oral squamous cell carcinoma patients of north-east India

BackgroundIn our study, we examined the 5-year survival of OSCC patients with HPV positive or negative status along with p16 protein expression. MethodA total of 72 biopsy tissue specimens from histologically confirmed oral squamous cell carcinoma (OSCC) patients were collected. HPV detection and genotyping were performed using HPV E6/E7 and HPV- type-specific multiplex primer for nested-PCR. Immunohistochemistry evaluation of pl6 was conducted. SPSS statistical software (ver 20) was used for data analysis. ResultsHigh risk-HPV (hr-HPV) DNA positivity was found in 27.7% (n = 20) of OSCC patients. Stage III OSCC patients were 7.80 times more likely to survive 5 years than stage IV patients (OR-7.80 CI-95%; P-0.03). Among the hr-HPV positive OSCC patients, we found that the median survival time for the 1st year (95%), 3 years (78.5%), and 5 years (38.5%) was significantly higher than that of the hr-HPV negative [1st year (78.6%), 3 years (45.2%) and 5 years (38.5%)] OSCC patients (P-0.03 The survival of male patients with hr-HPV positive OSCC is 9.75 times greater than the survival of patients with HPV negative OSCC (OR-9.75; CI-95%; P-0.05). The p16 expression level (low to overexpression) group and negative P16 expression group of OSCC patients have not demonstrated a significant association with 5-year survival. ConclusionWe conclude that in OSCC cases of North-East India, the presence of hr-HPV in OSCC cases could be a good predictor of 5-year survival rate. Expression of p16 does not appear to have any significant association with 5-year survival.

Logistic regression analysis of mRNA expression changes and prognosis after cervical surgery

Objective: The aim of this study was to investigate the diagnostic value of HPV (human papillomavirus) E6/E7 mRNA combined with thin-layer liquid-based cytology test (TCT) detection in patients with cervical intraepithelial neoplasia (CIN) in the residual and recurrence of lesions after cervical conization. Methods: A total of 154 patients who had undergone cervical conization and were diagnosed with high-grade cervical intraepithelial neoplasia (CIN 1 and CIN 3) by histopathology and had complete follow-up data were enrolled. TCT, HPV-DNA detection, and HPV E6/E7 mRNA detection combined with TCT detection in 12 months can be used to detect abnormal cytology (&amp;gt;atypical squamous epithelium of undetermined significance). Patients with atypical squamous cell of undetermined significance or high-risk HPV-DNA (+) or HPV E6/E7 mRNA combined with TCT (+) underwent colposcopy and cervical biopsy again for pathological diagnosis. Results: There were 9 cases of residual lesions and 22 cases of recurrence. Thirty of the 57 cases with positive HPV-DNA after surgery were still there or came back. Of the 26 cases with positive HPV E6/E7 mRNA combined with TCT, 24 were still there or came back. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy rate of HPV-DNA detection were 96.8%, 78.0%, 52.6%, 99.0%, and 81.8%, respectively; the sensitivity and specificity of HPV E6/E7 mRNA were combined with TCT detection of sex. Conclusion: HPV E6/E7 mRNA combined with TCT detection can be included in follow-up examinations, which can timely and effectively predict the risk of CIN residual or recurrence after cervical conization and reduce excessive examination and treatment.

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.

The Role of Human Papilloma Virus (HPV) in Primary Lung Cancer Development: State of the Art and Future Perspectives.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Notably, the incidence of lung cancer among never-smokers, predominantly women, has been rising in recent years. Among the various implicated risk factors, human papilloma virus (HPV) may play a role in the development of NSCLC in a certain subset of patients. The prevalence of high-risk HPV-DNA within human neoplastic lung cells varies across the world; however, the carcinogenetic role of HPV in NSCLC has not been completely understood. Bloodstream could be one of the routes of transmission from infected sites to the lungs, along with oral (through unprotected oral sex) and airborne transmission. Previous studies reported an elevated risk of NSCLC in patients with prior HPV-related tumors, such as cervical, laryngeal, or oropharyngeal cancer, with better prognosis for HPV-positive lung cancers compared to negative forms. On the other hand, 16% of NSCLC patients present circulating HPV-DNA in peripheral blood along with miRNAs expression. Typically, these patients have a poorly differentiated NSCLC, often diagnosed at an advanced stage. However, HPV-positive lung cancers seem to have a better response to target therapies (EGFR) and immune checkpoint inhibitors and show an increased sensitivity to platinum-based treatments. This review summarizes the current evidence regarding the role of HPV in NSCLC development, especially among patients with a history of HPV-related cancers. It also examines the diagnostic and prognostic significance of HPV, investigating new future perspectives to enhance cancer screening, diagnostic protocols, and the development of more targeted therapies tailored to specific cohorts of NSCLC patients with confirmed HPV infection.

Differential microRNA Expression Analysis in Patients with HPV-Infected Ovarian Neoplasms.

This study aimed to identify microRNAs (miRNAs) whose expression levels are altered by high-risk human papillomavirus (HR-HPV) infection in women with epithelial ovarian neoplasms. MiRNA expression was quantified by real-time polymerase chain reaction, while HR-HPV DNA was quantified using digital-droplet PCR. Analysis of 11 miRNAs demonstrated significantly lower hsa-miR-25-5p expression in HPV-infected compared to uninfected ovarian tissues (p = 0.0405), while differences in miRNA expression in corresponding serum were statistically insignificant. The expression of hsa-miR-218-5p in ovarian tumors was significantly higher in high-grade serous ovarian carcinoma (HGSOC) cases than in other neoplasms (p = 0.0166). In addition, hsa-miR-218-5p was significantly upregulated, whereas hsa-miR-191-5p was significantly downregulated in tissues with stage III/IV FIGO (p = 0.0009 and p = 0.0305, respectively). Using unsupervised clustering, we identified three unique patient groups with significantly varied frequencies of HPV16/18-positive samples and varied miRNA expression profiles. In multivariate analysis, high expression of hsa-miR-16-5p was an independent prognostic factor for poor overall survival (p = 0.0068). This preliminary analysis showed the changes in miRNA expression in ovarian neoplasms during HPV infection and those collected from HGSOCs or patients with advanced disease. This prospective study can provide new insights into the pathogenesis of ovarian neoplasms and host-virus interactions.

Оценка эффективности применения активированной глицирризиновой кислоты у пациенток с ВПЧ-ассоциированными поражениями шейки матки с учетом уровня половых стероидных и гонадотропных пептидных гормонов

Background: the persistence of human papillomavirus (HPV) infection with oncogenic protein expression causes changes in the stratified squamous epithelium, which is the immediate cause of cervical cancer manifestation. The use of the activated glycyrrhizic acid (GA) for HPV-associated cervical lesions is pathogenetically justified. During an experimental study on a culture of human cervical adenocarcinoma cells (HeLa line), it was shown that the antiproliferative effect of GA is enhanced by low concentrations of estradiol and weakened by testosterone. Aim: to evaluate the efficacy of the activated GA in female patients with HPV-associated cervical pathology with respect to the level of sex steroid and gonadotropin-releasing hormones Patients and Methods: a prospective study was conducted with the inclusion of 51 female patients with HPV-associated cervical pathology (ASCUS — atypical squamous epithelial cells of undetermined significance, LSIL — low-grade squamous intraepithelial lesion, HSIL— high-grade squamous intraepithelial lesion according to the Bethesda classification) and the absence of clinical and/or laboratory signs of hyperandrogenism. The following studies were performed: clinical examination, colposcopy, microscopic examination, cytology and immunocytochemistry, as well as hormonal status was evaluated. All female patients received Epigen Intim spray 0.1%, 3 times a day, for 30 days from the moment of inclusion in the study. If indicated, cervical conization was also performed. The treatment efficacy was evaluated 90±7 days after the therapy initiation based on the liquid-based HPV-PAP test results with the determination of p16/Ki67 oncogenic protein co-expression in the cervical epithelium. Changes in the colposcopy results were also evaluated. Results: it was found that the level of estradiol in patients with HSIL was lower versus the patients with ASCUS and LSIL (32 [32.0; 36.0] pg/ml versus 40 [34.5; 45.5] and 40 [33.0; 44.0] pg/ml, respectively, but the difference did not reach statistical significance (p=0.453). 90 days after the follow-up start, according to the cytology results of the cervical epithelium, 50 (98.0%) patients showed the absence of cervical intraepithelial lesions and the absence of p16/Ki67 oncogenic protein co-expression, 48 (94.1%) patients showed no high-risk (HR) HPV DNA, whereas HPV-associated colposcopy signs (anogenital warts, chronic cervicitis signs) persisted only in 6 (11.8%) patients. Conclusion: the use of activated GA in female patients of reproductive age with HPV-associated cervical lesions without clinical and/or laboratory signs of hyperandrogenism allowed to achieve high efficiency indicators: 98.5% — according to the cytology results, 83.3% — in reducing the HR-HPV viral load, 85.7% — in terms of p16/Ki67 oncogenic protein co-expression. KEYWORDS: human papillomavirus, squamous intraepithelial lesion of the cervix, oncogenic protein co-expression, sex steroid hormones, activated glycyrrhizic acid FOR CITATION: Mandrykina Zh.A., Dobrokhotova Yu.E., Ibragimova D.M., Kazieva M.D., Filimonova M.S., Shimanovsky N.L., Akhmetgaliev A.R. Assessment of the activated glycyrrhizic acid efficacy in female patients with HPV-associated cervical lesions with respect to the level of sex steroid and gonadotropin-releasing hormones. Russian Journal of Woman and Child Health. 2024;7(2):127–134 (in Russ.). DOI: 10.32364/2618-8430-2024-7-2-7.