High-risk Human Papillomavirus Subtypes Research Articles

Prevalence of 14 high-risk human papillomavirus subtypes among volunteers of cervical cancer screening by Papanicolaou smear cytology from a tertiary care institute of Assam, India

Abstract: BACKGROUND: In India, cervical cancer is the second most prevalent cancer among women, constituting 18.3% of all cases. Persistent high-risk human papillomavirus (HPV) infection is a well-established risk factor for cervical cancer. OBJECTIVES: This study aimed to assess the prevalence of 14 high-risk HPV subtypes and their association with abnormal cytology among women in Upper Assam. MATERIALS AND METHODS: This descriptive cross-sectional study was conducted from February 2022 to April 2023 at a tertiary care center in Assam. A total of 100 women aged 23-72 years underwent cervical sample collection for HPV DNA analysis via real-time polymerase chain reaction and cytological examination of Papanicolaou (PAP) smears. RESULTS: The overall HPV prevalence was 13%, with 10% testing positive for HPV 16/18 and 6% for other high-risk subtypes. Coinfection with HPV 16/18 and other subtypes was found in 3% of cases. The mean age of HPV-positive participants was 46 years. Cytology results showed 87% normal, 11% inflammatory changes, and 2% epithelial cell abnormalities. The Chi-square analysis (α = 0.05) showed no significant association between age (P = 0.24), religion (P = 0.49), or education (P = 0.57) and HPV positivity, but the study showed a significant association of HPV infection with menstrual cycle (P = 0.04). The study also showed a significant association between cervical cytology and HPV positivity (P = 0.0087). DISCUSSION: The present study’s findings on the prevalence of all 14 high-risk HPV subtypes contribute new insights to the existing literature, although the slightly lower prevalence may be attributed to the sample size and demographic factors. The findings emphasize the need for regular screening by PAP smear as well as by HPV DNA detection, as cytological abnormalities were detected even in those without HPV infection. CONCLUSION: Along with 16/18 HPV subtypes, a longitudinal study may offer important insights into the development of coinfections and the other 12 subtypes of HPV infection, as well as the spectrum of dysplasia and in situ cervical cancer.

Age distribution of patients with multiple High-Risk Human Papilloma Virus (HR-HPV) genotypes and HPV vaccine recommendations by age

Introduction: The aim of this study to identify the age distribution of patients with multiple high risk Human Papilloma Virus (HR-HPV) genotypes and to evaluate HPV vaccination programs through age distribution. Methods: Patients between the ages of 20-70, who had cervical screening (cervical smear) and HPV genotype tests between January 2017 and December 2021 in Gynecology and Obstetrics Department in Tınaztepe University Hospital, were included in this study. HR-HPV genotype tests and age information which were performed evaluated retrospectively. Results: The study consisted of 66 patients analysis with multiple HR-HPV genotypes. The median age of the patients with multiple HR- HPV was found to be 32.6 years old. The most frequent combination of multiple HR-HPV was found two sub-types of HR-HPV (66.7%), median age was found as 36.6 years old. In this study the frequency for three sub-types of HR-HPV was found 24.2% and median age for this group was found to be 34.7 years old. We found frequency in patients with four or more sub-types of HR-HPV as 9.1%, and the median age for this group as 33.1 years old was found. Conclusion: The most common cause of cervical cancer is HPV infection. Multiple HR-HPV infection progression may promote high risk cervical lesions and neoplasia. HPV genotype testing results considering combination of subtypes may direct individual treatment, follow-up protocols for patients. HPV vaccination research may comprise multiple HR-HPV subtypes relations and age distribution for optimal immunization.

Prevalence and genotype distribution of HPV combined with cervical pathological results in women from Sichuan, China: A cross-sectional study based on post-vaccination period 2019 to 2023.

Human papillomavirus (HPV) screening and vaccination exert efficacy in controlling the progression of cervical cancer. Thus, examinations into HPV prevalence, age-stratified specificity, genotype distribution, and their correlation with pathological outcomes can furnish robust evidence for customizing high-quality population screening and management. A cohort of 17,923 women attending clinics in the Jintang area, Sichuan, from January 2019 through August 2023 were enrolled in the study. Genotyping of HPV was conducted using real-time polymerase chain reaction (RT-PCR). The epidemiology and the relationship between HPV infection and histologic/cytologic abnormalities were subjected to analysis. HPV infection was identified in 4387 women. The outpatient group exhibited a significantly higher HPV infection rate compared to the healthy examination group (26.5% vs. 17.5%, p < 0.05). The distribution of infection rates across different age groups exhibited a U-shaped pattern, with the highest infection rate in the group ≤20 years of age, succeeded by those >60 years of age. The 31-40 age group demonstrated the lowest prevalence of infection, but upon infection, its prevalence of the precancerous lesion CIN2-3 reached a maximum of 29.0%, constituting a novel finding. The most prevalent genotype was HPV52, followed by HPV16, 58, 53, 68, and 18. In the cytologic and histologic abnormalities group, the most common types were HPV52, 16, and 58. HPV16 predominantly appeared in high-grade intraepithelial neoplasia and carcinoma insitu, constituting over 60% of cases. While HPV type 52 was not individually detected in cervical cancer cases. And some other non-vaccine-covered HPV subtypes also showed high prevalence in Sichuan. The single infection rates of NH9-HPV (high-risk HPV subtypes covered by the non-nine-valent vaccine) in CIN2-3 and cervical cancer patients were 6.5% and 2.6%, respectively. Among them, HPV51, HPV53, HPV59, and HPV35 exhibited a significant preponderance, which even higher than HPV45 and HPV31 covered by the nine-valent vaccine types. And in NL9-HPV (low-risk HPV subtypes covered by the non-nine-valent vaccine), HPV42 accounted for the highest percentage in CIN2-3. A similar decreasing trend was observed in annual infection rates in the healthy examination population and in the 31-40 and 51-60 age groups, while the ≤20 age group showed an increase. Regarding type-specificity, HPV16 and HPV58 exhibited the most rapid declines. This study furnishes the latest insights into the characteristics of HPV infection rate, age distribution, and genotype prevalence in Sichuan.

Do HPV 16 positive/ASC-H cervical cancer screening results predict CIN 2+ better than other high-risk HPV subtypes?

To determine whether patients with atypical squamous cells, cannot exclude high grade squamous intraepithelial neoplasia (ASC-H) cytology have a correlation between high-risk human papillomavirus (HPV) type and CIN 2+1 lesion in final pathology. The study was conducted retrospectively, using data from three tertiary gynecologic oncology centers located in various regions of Turkey. Data from 5,271 patients who had colposcopy between January 2003 and January 2021 were analyzed. A total of 163 patients who had ASC-H cervical cytology test results, based on the Bethesda 2014 classification were eligible, and of these 83 (50.9%) who tested positive for HPV were included in the study. There was no correlation between the occurrence of CIN 2+ lesions and age (p=0.053). If there was any HPV 16 positivity (only HPV 16, HPV 16 and 18, HPV 16 and others) the presence of CIN 2+ lesions in the final pathology increased significantly. In HPV 16 positive ASC-H patients, the probability of CIN 2+ lesions in the final pathology were 72.5% while this rate was 48.1% in HPV 16 negative group (p=0.033). The guidelines do not provide a comprehensive definition of the role of the HPV test in managing ASC-H. Positive high-risk HPV types, especially HPV 16, together with an ASC-H smear result should bring to mind the possibility of high-grade dysplasia.

Prevalence of high-risk human papillomavirus genotypes in outpatient Malian women living with HIV: a pilot study.

Long-term exposure to high-risk human papillomavirus (Hr-HPV) is a well-known necessary condition for development of cervical cancer. The aim of this study is to screen for Hr-HPV using vaginal self-sampling, which is a more effective approach to improve women's adherence and increase screening rates. This pilot study included a total of 100 Women living with HIV (WLWHIV), recruited from the Center for Listening, Care, Animation, and Counseling of People Living with HIV in Bamako. Hr-HPV genotyping was performed on Self-collected samples using the Cepheid GeneXpert instrument. The median age of WLWHIV was 44 (interquartile range [IQR], 37-50) years. Approximately 92% of the study participants preferred self-sampling at the clinic, and 90% opted to receive result notifications via mobile phone contact. The overall prevalence of Hr-HPV among study participants was 42.6%, and the most frequent Hr-HPV sub-types observed were HPV18/45 (19.1%), HPV31/35/33/52/58 (13.8%), and HPV39/68/56/66 (12.8%), followed by HPV16 (5.3%), and HPV51/59 (5.3%). WLWHIV under 35 years of age had a higher frequency of Hr-HPV compared to their older counterparts, with rates of 30% versus 11.1% (p = 0.03). The duration of antiretroviral treatment showed an inverse association with Hr-HPV negativity, with patients on treatment for 15 (IQR, 10-18) years versus 12 (IQR = 7-14) years for Hr-HPV positive patients (95% CI [1.2-5.8], t = 3.04, p = 0.003). WLWHIV with baseline CD4 T-Cell counts below 200 exhibited a higher frequency of Hr-HPV compared to those with baseline CD4 T-Cell counts above 200 (17.9% versus 1.9%, p = 0.009). However, other demographics and clinical factors, such as marital status, age of sexual debut, parity, education, history of abortion, history of preeclampsia, and cesarean delivery, did not influence the distribution of Hr-HPV genotypes. Our findings indicate that WLWHIV under the age of 35 years old exhibited the highest prevalence of Hr-HPV infection, with HPV18/45 being the most prevalent subtype. Additionally, WLWHIV with baseline CD4 T-Cell counts below 200 showed the highest infection rates.

Human Papillomavirus Is Rare and Does Not Correlate with p16INK4A Expression in Non-Small-Cell Lung Cancer in a Jordanian Subpopulation.

Background and Objectives: Human papillomavirus (HPV) was previously investigated in lung cancer with wide inter-geographic discrepancies. p16INK4a has been used as a surrogate for detecting high-risk HPV (HR-HPV) in some cancer types. This study assessed the evidence of HPV in non-small-cell lung cancer (NSCLC) among Jordanian patients, investigated the expression of p16INK4a, and evaluated its prognostic value and association with HPV status. Materials and Methods: The archived samples of 100 patients were used. HPV DNA detection was performed by real-time polymerase chain reaction (RT-PCR). p16INK4a expression was assessed by immunohistochemistry (IHC). The Eighth American Joint Committee on Cancer protocol (AJCC) of head and neck cancer criteria were applied to evaluate p16INK4a positivity considering a moderate/strong nuclear/cytoplasmic expression intensity with a distribution in ≥75% of cells as positive. Results: HPV DNA was detected in 5% of NSCLC cases. Three positive cases showed HR-HPV subtypes (16, 18, 52), and two cases showed the probable HR-HPV 26 subtype. p16INK4a expression was positive in 20 (20%) NSCLC cases. None of the HPV-positive tumors were positive for p16INK4a expression. A statistically significant association was identified between p16INK4a expression and the pathological stage (p = 0.029) but not with other variables. No survival impact of p16INK4a expression was detected in NSCLC cases as a group; however, it showed a statistically significant association with overall survival (OS) in squamous cell carcinoma (SqCC) cases (p = 0.033). Conclusions: This is the first study to assess HPV and p16INK4a expression in a Jordanian population. HPV positivity is rare in NSCLC among a Jordanian subpopulation. P16 INK4a reliability as a surrogate marker for HPV infection in lung cancer must be revisited.

Incidence of oncogenic HPV infection in women with and without mental illness: A population-based cohort study in Sweden.

Women with mental illness experience an increased risk of cervical cancer. The excess risk is partly due to low participation in cervical screening; however, it remains unknown whether it is also attributable to an increased risk of infection with human papillomavirus (HPV). We aimed to examine whether women with mental illness had an increased infection rate of HPV compared to women without mental illness. Using a cohort design, we analyzed all 337,116 women aged 30 to 64 and living in Stockholm, who had a negative test result of 14 high-risk HPV subtypes in HPV-based screening, during August 2014 to December 2019. We defined women as exposed to mental illness if they had a specialist diagnosis of mental disorder or had a filled prescription of psychotropic medication. We identified incident infection of any high-risk HPV during follow-up and fitted multivariable Cox models to estimate hazard ratios (HR) with 95% confidence intervals (CI) for HPV infection. A total of 3,263 women were tested positive for high-risk HPV during follow-up (median: 2.21 years; range: 0 to 5.42 years). The absolute infection rate of HPV was higher among women with a specialist diagnosis of mental disorder (HR = 1.45; 95% CI [1.34, 1.57]; p < 0.001) or a filled prescription of psychotropic medication (HR = 1.67; 95% CI [1.55, 1.79]; p < 0.001), compared to women without such. The increment in absolute infection rate was noted for depression, anxiety, stress-related disorder, substance-related disorder, and ADHD, and for use of antidepressants, anxiolytics, sedatives, and hypnotics, and was consistent across age groups. The main limitations included selection of the female population in Stockholm as they must have at least 1 negative test result of HPV, and relatively short follow-up as HPV-based screening was only introduced in 2014 in Stockholm. Mental illness is associated with an increased infection rate of high-risk HPV in women. Our findings motivate refined approaches to facilitate the WHO elimination agenda of cervical cancer among these marginalized women worldwide.

Abstract 2142: Spatial distribution of high-risk human papillomavirus (HR-HPV) across 23 Chicago community areas and correlates

Abstract Background: Despite availability of effective vaccines and screening, cervical cancer claimed 4,280 lives in 2022. We explored the spatial distribution of high-risk human papillomavirus (“HR-HPV”) infection across 23 Chicago Community Areas (CCAs) served by the University of Illinois Health Network (UI Health). Using a modified Warnecke et al Health Disparity Outcomes (HDO) model, we hypothesized that CCAs with higher rates of structural violence, the social, economic, and political systems exposing populations to risks and vulnerabilities, would correlate with increased HR-HPV. Methods: Electronic medical records of patients receiving routine cervical cancer screening between January 1, 2015 and December 31, 2019 were reviewed. As per the 2014 ACS guidelines. HR-HPV test results were captured as HR-HPV positive, HR-HPV-16, HR-HPV-18 and non-16/18 HR-HPV, the latter consisting of 12 HR-HPV subtypes. Structural violence variables were used from Chicago Health Atlas (2015-2019) with percent poverty, hardship index score, easy access to fruit and vegetables, routine checkup, homicide, and primary care provider across CCAS. Univariate Poisson regression was used to compare the associations between selected structural violence factors and HR-HPV prevalence. Univariate multinomial logistic regression evaluated associations between structural violence indicators and HR-HPV subtypes Global p-values were obtained using ANOVA at 0.05 significance. Results: 8,566 women met inclusion criteria out of 13,466 total women. 75% were Black or Hispanic. Overall prevalence of cervical HR-HPV infection was 20.3% (n=1,737), ranging from 8.7% to 27.2% across CCAs. Median age for women was 36. Percent with primary care provider was negatively associated with HPV infection (IRR = 0.99 with 95% CI (0.98, 1.00), adjusted p-value=0.023), indicating women living in CCAs with higher rates of primary care provider were less likely to have HR-HPV. Easy access to fruit and vegetables (adjusted p-value = 0.007) and percent with primary care provider (adjusted p-value = 0.009) were significantly associated with HR-HPV subtypes. Women living in CCAs with easy access to fruit and vegetables (OR = 0.99, with 95% CI (0.98,0.99)) as well as those with higher rates of primary care provider (OR = 0.98, with 95% CI (0.97,0.99)) were less likely to have non-16/18 HR-HPV. Conclusion: HR-HPV is the most common sexually transmitted infection, and most women clear the infection naturally. As the origin of 99% of cervical cancer, understanding the reasons HR-HPV persists and progresses to cancer among certain individuals and groups is critical. Novel interventions like increasing access to fruit and vegetables could compliment widely available and effective vaccines. Citation Format: Gelila Goba, Jiehuan Sun, Quetzal Class, Joel Schwartz, Sage Kim, Karriem Watson, Lisa Tussing-Hummphreys, Yamile Molina, Shannon MacLaughlan, Ziqiao Xu, Benjamin Aldred, Subhash Kumar Kolar Rajanna, Tamika Alexander, Anna-Barbara Moscicki. Spatial distribution of high-risk human papillomavirus (HR-HPV) across 23 Chicago community areas and correlates [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 2142.

Research and future directions of HPV-related vaccines

Human papillomavirus (HPV) infection is a major cause of cervical lesions such as cervical cancer in women. Prophylactic vaccines developed against HPV have been widely used, but these vaccines are only effective against certain types of HPV and do not work in people who are already infected. Therefore, the development of therapeutic vaccines is also particularly important. The use of the modified poxvirus (MVA) as a vector for HPV vaccinations has garnered attention in recent years. It has been found that modified poxvirus vaccines are able to combat human papillomavirus infection and have significant safety and efficacy profiles. Based on the study of the distribution of HPV types in different regions and populations, this paper finds that there are differences in the prevalence of high-risk HPV subtypes in different regions, and that a large number of infected people need more effective treatments. At the same time, by comparing the advantages and disadvantages of preventive and therapeutic vaccines, we recognize that both have roles that cannot be replaced by the other in the task of fighting HPV, and that the two vaccines need to be developed together and complement each other in order to minimize the harm of HPV. Based on these findings, this paper provides a constructive reference for future targeted prevention and treatment of HPV in different regions of the world with different HPV distributions.

Vaccination and modern therapy of cervical cancer

Cervical cancer is the fourth most common cancer in women worldwide and is responsible for over 300 thousand deaths worldwide. The causative agent of cervical cancer is persistent infection with high-risk human papillomavirus subtypes, and viral oncoproteins E 5, E 6, and E 7 interact with human factors to induce and maintain a malignant phenotype. This review describes the mechanisms behind the onset and development of cervical cancer and discusses in detail promising and effective new treatment options for cervical cancer, including immunotherapy, targeted therapy and combination therapy.

Evaluation of AI-assisted colposcopy for detecting high-risk subtypes of human papillomavirus in CIN2

Evaluation of AI-assisted colposcopy for detecting high-risk subtypes of human papillomavirus in CIN2

Human Papilloma Virus Infection and Gene Subtypes Analysis in Women Undergoing Physical Examinations: A 2015-2020 Study in Wenzhou, China.

Persistent infection with high-risk human papillomavirus (HPV) is closely related to cervical cancer. The epidemiologic characteristics of cervical HPV have regional differences. Therefore, it is necessary to develop the most favorable policies according to the actual situation of each region to prevent and reduce the prevalence of cervical cancer. This retrospective cross-sectional study investigated the prevalence, gene subtypes, and temporal trends of HPV in women undergoing physical examination in Wenzhou, to provide a decision-making basis for further prevention and control of HPV. A total of 31131 cervical exfoliated cell specimens obtained from physical examinations in Wenzhou, a coastal city of China, from 2015 to 2020 were collected. The age distribution was analyzed using the chi-squared test, and the time change trend was analyzed using the Mann-Kendall trend test. On this basis, the distribution characteristics of the HPV subtypes were analyzed. The total prevalence rate was 9.55%, and the prevalence rate in different age groups ranged from 7.77% to 14.16%. The prevalence rate in different years was 8.84%-11.83%. The prevalence rate was bimodal; it was highest in the group 25years old, followed by the group >61years old. The top five high-risk gene subtypes were HPV52, HPV58, HPV53, HPV16, and HPV39, whereas the low-risk subtypes were HPV61, HPV81, HPV44, HPV43, and HPV55. Of all the positive samples, 76.03% were infected with a high-risk subtype. Most female HPV patients in Wenzhou are infected with high-risk gene subtypes. Therefore, physical examination and screening for HPV should be further strengthened, and the corresponding vaccination policy should focus on high-risk gene subtypes.

Pleomorphic Adenoma With Cystic Change, Extensive Squamous Metaplasia and Positive Block-Like p16 Staining Pattern: A Sheep In Wolf’s Clothing

Abstract Introduction/Objective Pleomorphic adenoma, the most common benign salivary gland neoplasm may show squamous metaplasia in up to 25% of cases, and less frequent cystic change. We report an unusual case of pleomorphic adenoma with cystic change, extensive squamous metaplasia and block-like p16 staining that was misdiagnosed as metastatic p16-positive squamous cell carcinoma in a limited core biopsy. Methods/Case Report A 78-year-old female with no history of malignancy presented with a right neck painless mass. PET-CT demonstrated a hypermetabolic ovoid mass adjacent to the right submandibular gland measuring 1.7 cm concerning for metastatic disease within a lymph node. Fine needle aspiration of lesion was hypocellular and showed cystic contents and rare atypical squamoid cells. Core biopsy of the lesion demonstrated sheets of squamoid cells with mild to moderate cytologic atypia in a hyalinized fibrotic stroma. Immunostain for p16 showed cytoplasmic and nuclear block-staining pattern. The biopsy was diagnosed as metastatic p16-positive squamous cell carcinoma. Subsequent human papilloma virus (HPV) in situ hybridization for low- and high-risk types was negative. The patient underwent right level 1B neck dissection revealing a pleomorphic adenoma arising at the periphery of the submandibular gland with cystic change and extensive central squamous metaplasia. Repeated p16 staining showed diffuse positivity in the area with squamous metaplasia and heterogenous staining in the non-metaplastic areas. Cobas HPV-PCR test covering 14 high-risk HPV subtypes was also negative. Results (if a Case Study enter NA) NA Conclusion We describe the unusual coexistence of extensive squamous metaplasia, cystic change and aberrant p16 staining pattern in an exophytic pleomorphic adenoma to raise awareness of how these changes individually, and more so in combination can mimic squamous cell carcinoma. The mechanism of p16 overexpression in metaplastic PAs appears to be independent of HPV infection.

Genomic Characterization of Cervical Tumors Driven by Rare High-Risk HPV Subtypes Utilizing a Deep Learning Framework

As many as 30-50% of patients with locally advanced cervical cancer (LACC) experience recurrence after chemoradiation therapy (CRT). More sophisticated prognostic schemes and targeted therapeutic options are urgently needed. Human papillomavirus (HPV) is responsible for the majority of invasive cervical carcinomas, most commonly HPV 16 and 18 subtypes. In large part due to their rarity, little is known about the biologic behavior of LACC driven by non-16/18 HPV genotypes. We hypothesized that rare HPV subtypes drive distinct gene expression patterns. To aid in the common dilemma of limited sample procurement, we developed a tool which leverages population data and generative adversarial neural network (GAN) modelling to exploit patterns of gene expression of small phenotypic groups for downstream analysis. Here, we employed a deep learning approach to identify gene expression patterns unique to tumors caused by rare HPV subtypes. Whole transcriptome analysis of tumor biopsies from an institutional LACC tumor bank were employed including 130 HPV16/18 positive, and at least 3 each of rare HPV subtypes 31, 33, 39, 45, 52, 58, and 59. A Wasserstein GAN model (WGAN) was trained for each rare HPV subtype, and used to generate augmented rare HPV population data for downstream differential expression testing between rare HPV subtypes and HPV16/18. K-means clustering analysis was performed using R stats package. Differential gene expression testing between rare HPV subtype populations was performed using the EdgeR R-package. Pathway Enrichment analysis was conducted using EnrichR software. By minimizing intergroup clustering distance, 3 clusters of HPV driven disease were demonstrated. The first cluster demonstrated biology similar to HPV16 and HPV18. Namely, pathway enrichment analysis performed on lists of differentially expressed genes between GAN augmented rare HPV subtypes (HPV45, HPV52, and HPV58) and classical HPV subtypes 16 and 18, yielded no significant statistical differences. The second cluster demonstrated enriched gene expression in proinflammatory IL-1 and IL-6 family cytokines and focal adhesion signaling (HPV31, HPV33, HPV39) (IL-1 regulation of extracellular matrix, p = 5.0e-6; Oncostatin M signaling, p = 2.0e-7; Integrin Signaling, 2.5e-7). The last cluster demonstrated an increased Th2/myeloid signature (HPV59) (T helper cell surface molecules 1.2e-7, myeloid cell signature 8.5e-9). Utilizing a deep learning architecture to model gene expression of rare HPV subtypes we demonstrate 3 groups of HPV driven cervical cancer biology. These groups include a classical subtype, a high IL-1/IL-6 high subtype, and a myeloid associated subtype. Knowledge of such tumor heterogeneity can aid in the future development of targeted treatment plans and patient prognosis.

Four-year analysis of high-risk human papillomavirus infection among women in rural areas of Nyingchi City, Tibet.

This study aims to address the existing data gap regarding the status of high-risk human papillomavirus (HR-HPV) infection and the distribution of HR-HPV subtypes among women in rural areas of Nyingchi City, Tibet. The research objectives include providing insights for HPV vaccine development. The research collected data from two rounds of cancer screening conducted among rural women in Nyingchi City, Tibet, from 2019 to 2022. HR-HPV subtype gene detection was performed using the PCR fluorescence method on the collected samples. And then analyzed the HR-HPV infection rate among rural women in Nyingchi City, Tibet, as well as the infection rate of different HR-HPV subtypes and their distribution across different age groups. A comparison was made between the infection rates of women in rural areas outside the Qinghai-Tibet Plateau and those in Nyingchi City. A total of 15,687 cases included. The overall HR-HPV infection rate among women in rural areas of Nyingchi City, Tibet, was 13.00% (2040/15,687), which was significantly higher than the rate among women in rural areas outside the Qinghai-Tibet Plateau (7.82% (9,249/118,237); χ2 = 635.7, p < 0.001). The highest HPV infection rate was observed in the 35-39 age group, with a rate of 15.31% (499/3260), which was significantly higher than the rate of 7.22% (1827/25,322) among women in the same age group in rural areas outside the Qinghai-Tibet Plateau (χ2 = 253.00, p < 0.001). The lowest HPV infection rate was found in the 50-54 age group, with a rate of 9.69% (246/2540), which was statistically different from the rate of 8.14% (1,604/19,698) among women in the same age group outside the Qinghai-Tibet Plateau (χ2 = 17.68, p < 0.001). The top three HR-HPV subtypes among women in rural areas of Nyingchi City, Tibet, were HPV52 (20.15%, 411/2040), HPV16 (12.45%, 254/2040), and HPV58 (11.96%, 244/2040). These findings align with the top three HR-HPV subtypes among women in rural areas outside the Qinghai-Tibet Plateau. Furthermore, the top three HR-HPV subtypes among women aged 35-39, 40-44, and 45-49 in rural areas of Nyingchi City, Tibet, were HPV52, HPV16, and HPV58. In conclusion, the HR-HPV infection rate among women in rural areas of Nyingchi City, Tibet, is significantly higher compared to women in rural areas outside the Qinghai-Tibet Plateau, with consistent patterns observed in the distribution of the top three HR-HPV subtypes between the two regions.

Clinical Efficacy and Safety of AdV-tk Gene Therapy for Patients with Cervical Squamous Intraepithelial Lesion: A Prospective Study.

Cervical cancer is the fourth most common type of cancer for women in 2020, and many more women have cervical pre-cancerous lesion-squamous intraepithelial lesion (SIL). Early treatment of cervical SIL to reverse or delay its progression is an important approach to reduce the incidence of cervical cancer. The efficacy and safety of adenovirus-based vectors expressing the thymidine kinase gene (AdV-tk) in the treatment of multiple types of cancers shows promise for its use in gynecology. We aim to provide relevant clinical efficacy and safety data after introducing AdV-tk for the treatment of cervical SIL for the first time through this prospective study. We conducted a maximum of 6-sessions to administer AdV-tk gene therapy to 23 patients (mean age: 35 years old) with cervical low-/high-grade SIL (LSIL/HSIL) who were enrolled from August 2015 to April 2018 and analyzed the clinical characteristics and follow-up outcomes (mean follow-up period: 7.3 months). The present study consisted of 17 patients (73.9%) with cervical HSIL and six patients with LSIL confirmed by colposcopy-directed biopsy. We observed an overall histological remission and regression rate of 87.0% (20/23, 95% confidence interval [95%CI]: 73.2-100%, P<0.001) after AdV-tk gene therapy. Eight patients (34.8%) were detected with human papillomavirus (HPV) 16/18 subtypes and 13 patients were found to be positive with at least one of the other 13 high-risk HPV (HR-HPV) subtypes, while two patients did not have any of the 15 HR-HPV subtypes. The overall clearance rate of HR-HPV was 76.2% (16/21, 95%CI: 58.0-94.4%, P=0.016) after AdV-tk gene therapy. For safety evaluation, no severe complications were reported in any of the 23 patients. The most commonly reported symptom was fever in 52.2% (12/23) of patients and all symptoms were fully resolved after symptomatic treatment. Our data indicates that AdV-tk gene therapy has high efficacy and safety in the treatment of cervical SIL among gynecological patients. Our findings provide clinical evidence on the potential promotion and application of AdV-tk in the treatment of cervical SIL, and potentially for cervical cancer, among gynecological patients.

Rate of Involved Endocervical Margins According to High-Risk Human Papillomavirus Subtype and Transformation Zone Type in Specimens with Cone Length ≤ 10 mm versus > 10 mm-A Retrospective Analysis.

The aim of this study was to evaluate the endocervical margin status according to transformation zone (TZ) and high-risk HPV (hr-HPV) subtype in specimens with cone length ≤ 10 mm versus > 10 mm to provide data for informed decision making and patients counseling especially for women wishing to conceive. In this retrospective cohort study, 854 patients who underwent large loop excision of the transformation zone during a nine-year period (2013-2021) for cervical disease were analyzed. The main outcome parameters were excision length, histological result, TZ type, HPV subtype and endocervical margin status. A subgroup analysis was performed according to excision length, with a cut-off value of 10 mm. A two-step surgical procedure was performed in case of an excision length of > 10 mm. The overall rate of positive endocervical margins irrespective of excision length was 17.2%, with 19.3% in specimens with ≤ 10 mm and 15.0% with > 10 mm excision length. Overall, 41.2% of women with a visible TZ and HPV 16/hr infection and 27.0% of women with HPV 18 received an excisional treatment of > 10 mm length without further oncological benefit, respectively. In contrast, assuming that only an excision of ≤ 10 mm length had been performed in women with visible TZ, the rate of clear endocervical margins would have been 63.7% for HPV 16/hr infections and 49.3% for HPV 18 infections. In conclusion, the decision about excision length should be discussed with the patient in terms of oncological safety and the risk of adverse pregnancy events. An excision length > 10 mm increases the number of cases with cervical tissue removed without further oncological benefit, which needs to be taken into account in order to provide an individual therapeutic approach. Furthermore, HPV 18 positivity is related to a higher rate of positive endocervical margins irrespective of TZ.

The correlation between multiple HPV infections and the occurrence, development, and prognosis of cervical cancer.

Cervical carcinoma is the fourth female malignant tumor in the world, and the persistent infection of high-risk human papillomavirus (HPV) is recognized as the most common cause. This article studies the correlation between multiple HPV infections and the occurrence, development, and prognosis of cervical cancer in order to provide more references for clinical diagnosis and treatment. We conducted a retrospective analysis of the clinical data of 400 cervical carcinoma patients admitted to our hospital from 2015 to 2023. The collected patient data include age, HPV infection status, tumor size and morphology, local infiltration depth, diagnostic staging, surgical approach, vascular cancer thrombus status, lymph node status, and postoperative HPV follow-up status. We use SPSS statistical software for data analysis. Our research shows that the high-risk age group for cervical carcinoma is concentrated between 41 and 60 years old, which is basically consistent with the age range of the high incidence of HPV infection. In the statistics for HPV infection types, ~67.7% of patients are single HPV-infected, 25.29% are double infected, and 7.00% are infected with three or more types of HPV. Among the multiple HPV infections, most of the patients are younger than 40 years old and older than 70 years old, with double infection accounting for the majority. The top five HPV subtypes with high detection rates belong to high-risk subtypes, which are the HPV16, 18, 58, 33, and 52 subtypes, respectively. There was no significant relationship between multiple HPV infections and cervical cancer stage, lesion size, pathological tissue type, tissue differentiation degree/vascular cancer thrombus, and lymph node metastasis, and there was no significant difference in the results between the groups. In summary, multiple types of HPV infection in the cervix are common. We found that multiple infections, mainly HPV16, are closely related to cervical cancer. For the HPV16, 18, 58, 33, and 52 subtypes of infection, especially for patients younger than 40 years old and older than 70 years old, priority should be given to prevention and treatment. The relationship between multiple HPV infections and the progression and prognosis of cervical carcinoma requires further research, which could better guide cancer prevention and treatment.

Prevalence of High-Risk HPV Subtypes and Efficacy of the HPV Vaccine in Preventing Cervical Epithelial Lesions: Survey and Insights from a German Study.

Historically, cervical cytology has been the standard method for detecting dysplastic cervical changes. However, extensive research has established that human papillomavirus (HPV) infection is a primary cause of these changes, necessitating a shift in screening and preventive strategies towards the molecular detection of high-risk HPV subtypes. To combat HPV infection, prophylactic vaccines have been developed, including the nonavalent, quadrivalent, and bivalent vaccines. An essential criterion for an effective HPV vaccine is to provide comprehensive coverage against the most prevalent high-risk HPV types associated with cervical cancer, ensuring optimal efficacy in preventing cervical lesions. Long-term protection against these types is crucial for effective prevention strategies; Material and Methods: A cohort of 210,510 women's samples was included in the analysis conducted within one year of implementing a screening program in Germany. The screening program involved the molecular detection of high-risk HPV subtypes, targeting specific age groups. The cohort comprised 63,710 women below 35 years of age and 146,800 women aged 35 years and above. The selection of high-risk HPV subtypes followed the guidelines provided by Becton-Dickinson. This study focused exclusively on cases with a documented history of vaccination, which were categorized into two main groups: Group I consisted of vaccinated individuals under 35 years old (12,765 cases), while Group II comprised vaccinated individuals aged 35 years and above (296 cases); Results: The HPV types HPV56/59/66 were found to be widely distributed across all age groups, with certain age groups exhibiting a higher incidence compared to HPV16 and HPV18. Similarly, HPV35/39/69, along with HPV31 and HPV45, were also observed to have a broad distribution among women. The incidence of high-grade squamous intraepithelial lesions (HSIL), including both CIN2 and CIN3, varied between 0.076% and 0.5% across all age groups, regardless of the individuals' vaccination status; Aim of the study: Our study provides valuable insights into the distribution, incidence, and prevalence of various high-risk HPV subtypes, including HPV56/59/66, HPV33/58, HPV35/39/68, and HPV45, in relation to precancerous cervical lesions. These subtypes are not adequately covered by the currently available HPV vaccines. Addressing the discrepancies between the prevalent HPV subtypes and existing vaccines is crucial in developing an ideal HPV vaccine that offers comprehensive protection. Tailoring screening programs and vaccination strategies to the local distribution of HPV subtypes is essential for effective prevention. By raising awareness and implementing targeted preventive measures, including vaccination, we can significantly reduce the incidence of precancerous and cancerous cervical lesions.

Evaluation of the efficacy and safety of Nocardia rubra cell wall skeleton immunotherapy for cervical high-risk HPV persistent infection

Objective: To evaluate the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) in the treatment of persistent cervical high-risk human papillomavirus (HR-HPV) infection. Methods: A randomized, double blind, multi-center trial was conducted. A total of 688 patients with clinically and pathologically confirmed HR-HPV infection of the cervix diagnosed in 13 hispital nationwide were recruited and divided into: (1) patients with simple HR-HPV infection lasting for 12 months or more; (2) patients with cervical intraepithelial neoplasia (CIN) Ⅰ and HR-HPV infection lasting for 12 months or more; (3) patients with the same HR-HPV subtype with no CINⅡ and more lesions after treatment with CINⅡ or CIN Ⅲ (CINⅡ/CIN Ⅲ). All participants were randomly divided into the test group and the control group at a ratio of 2∶1. The test group was locally treated with Nr-CWS freeze-dried powder and the control group was treated with freeze-dried powder without Nr-CWS. The efficacy and negative conversion rate of various subtypes of HR-HPV were evaluated at 1, 4, 8, and 12 months after treatment. The safety indicators of initial diagnosis and treatment were observed. Results: (1) This study included 555 patients with HR-HPV infection in the cervix (included 368 in the test group and 187 in the control group), with an age of (44.1±10.0) years. The baseline characteristics of the two groups of subjects, including age, proportion of Han people, weight, composition of HR-HPV subtypes, and proportion of each subgroup, were compared with no statistically significant differences (all P>0.05). (2) After 12 months of treatment, the effective rates of the test group and the control group were 91.0% (335/368) and 44.9% (84/187), respectively. The difference between the two groups was statistically significant (χ2=142.520, P<0.001). After 12 months of treatment, the negative conversion rates of HPV 16, 18, 52, and 58 infection in the test group were 79.2% (84/106), 73.3% (22/30), 83.1% (54/65), and 77.4% (48/62), respectively. The control group were 21.6% (11/51), 1/9, 35.1% (13/37), and 20.0% (8/40), respectively. The differences between the two groups were statistically significant (all P<0.001). (3) There were no statistically significant differences in vital signs (body weight, body temperature, respiration, pulse rate, systolic blood pressure, diastolic blood pressure, etc.) and laboratory routine indicators (blood cell analysis, urine routine examination) between the test group and the control group before treatment and at 1, 4, 8, and 12 months after treatment (all P>0.05); there was no statistically significant difference in the incidence of adverse reactions related to the investigational drug between the two groups of subjects [8.7% (32/368) vs 8.0% (15/187), respectively; χ2=0.073, P=0.787]. Conclusion: External use of Nr-CWS has good efficacy and safety in the treatment of high-risk HPV persistent infection in the cervix.