Virology Journal

The most common combination of co-infections genotypic distribution and clearance patterns of high-risk human papillomavirus in Southern China: a population-based retrospective study

High-risk human papillomavirus (HR-HPV) infection is a well-established cause of cervical cancer. This study aimed to investigate the distribution of HR-HPV genotypes and the infection patterns in the southern Chinese population to provide data to support effective strategies for HPV screening, prevention, and vaccination. We conducted a retrospective analysis of HPV genotyping results collected between January 2020 and December 2024. The study examined the distribution of HPV genotypes, the prevalence of single versus multiple infections, and the viral clearance patterns among affected individuals. A total of 196,103 samples were included in the analysis. The HR-HPV positivity rate was 16.91% and remained consistent over the five years. While a decrease in the positivity rate was observed for HPV-16 and HPV-18, no significant changes were observed for other genotypes. The most commonly detected HR-HPV genotypes were HPV-52, HPV-53, and HPV-58. Among all positive cases, 82.08% were single genotype infections, and 17.92% were multi-genotype infections. The most common co-infection combination was HPV-52 and HPV-53. The median time to viral clearance was 13.45 months. In particular, HPV-16/18 infections cleared more quickly than other genotypes. In contrast, multiple infections took longer to clear and were often resolved by elimination of multiple genotypes. HR-HPV infections in southern China have unique regional characteristics. These findings contribute to a deeper understanding of HPV epidemiology in the region and may help guide future efforts in HPV vaccination and cervical cancer prevention.

Human papillomavirus infections among women with cervical lesions and cervical cancer in Yueyang, China: a cross-sectional study of 3674 women from 2019 to 2022

Abstract Purpose To investigate the distribution of the incidence and genotypes of human papillomavirus (HPV) among women with cervical cancer (CC) and precancerous cervical lesions in Yueyang City, China, to develop prevention and control strategies for CC. Methods A total of 3674 patients with cervical lesions and cervical cancer who attended 7 hospitals in Yueyang City between September 2019 and September 2022 were included. They included 1910 cervical intraepithelial neoplasia (CIN) I, 718 CIN II, 576 CIN II and 470 CC, respectively. The HPV genotyping of the above patients was detected by Real time-PCR in the laboratory department of each hospital. Results The total HPV prevalence was 74.69% (95% CI 73.28–76.09%) in 3674 patients. The incidence of high- and low-risk HPV was 73.46% and 7.21%, respectively. The prevalence of HPV in CIN I, CIN II, CIN III, and invasive CC (ICC) groups was 66.65% (1273/1910, 95% CI 64.53–68.77%), 80.78% (580/718, 95% CI 77.89–83.67%), 83.88% (483/576, 95% CI 80.84–86.87%), and 86.81% (408/470, 95% CI 83.74–89.88%), respectively. The top three HPV subtypes in ICC are HPV16, HPV52, and HPV58. The prevalence of HPV 16 increased with increasing disease severity, with this genotype being present in 12.57%, 20.89%, 36.98%, and 50.85% of CIN I, CIN II, CIN III, and ICC cases, respectively ( p  < 0.001). Single HPV infection was predominant in cervical lesions, with a prevalence of 48.50% (95% CI 46.89–50.12%). The HPV prevalence varied by age, being highest among women with ICC, CIN I, CIN II and CIN III aged ≥ 60 years, 50–59 years, 40–49 years, and 40–49 years, respectively. Conclusion The prevalence of HPV in patients with cervical lesions in Yueyang City was very high, with HPV 16, 52, 58, 53, and 51 being the five most common HPV genotypes in patients with cervical lesions.

HPV and vaginal microecological disorders in infertile women: a cross-sectional study in the Chinese population

Abstract Background The purpose of this study was to evaluate the distributions of vaginal microbiome dysbiosis and human papillomavirus (HPV) subtypes in infertile women and explore the correlations of HPV infection and vaginal microbiome dysbiosis with infertility. Methods In total, 1464 women aged 18–50 years were included in this study; 649 participants were included in the infertility group, and 815 participants were included in the normal group. The participants were tested for HPV, and their vaginal microecology was examined. The χ2 test and Spearman regression were used for statistical analysis, and binary logistic regression was performed to identify the risk factors for infertility. Results The patients in the infertility group were younger than those in the normal group, and the proportions of bacterial vaginosis and vaginal imbalance in the infertility group were significantly higher than those in the normal group. The incidence proportions of high-risk HPV types in the infertility group were significantly higher than those in the normal group, and the proportions of high-risk subtytes HPV16, HPV39, HV52, HPV56, and HPV68 were significantly higher in the infertility group than in the normal group. However, there were no significant differences in the incidences of low-risk HPV types. The incidence proportions of vaginal flora imbalance and HPV infection in the infertility group were significantly higher than those in the normal group. HPV16, HPV33, HPV51, HPV52and HPV58 infections were independent risk factors for infertility. Conclusions Vaginal microecological imbalance and HPV infection are directly related to infertility, and precautions should be taken.

Increased expression of TIGIT and KLRG1 correlates with impaired CD56bright NK cell immunity in HPV16-related cervical intraepithelial neoplasia

Abstract Background The onset and progression of cervical intraepithelial neoplasia (CIN) are closely associated with the persistent infection of high-risk HPV (especially type16), which is mainly caused by immune escape. Natural killer (NK) cells play an important role against virally infected cells and tumor cells through a fine balance of signals from multiple surface receptors. Overexpression of non-MHC-I specific inhibitory receptors TIGIT, KLRG1, Siglec-7, LAIR-1, and CD300a on NK cells correlates with cellular exhaustion and immune evasion, but these receptors have not been investigated in CIN. The aim of the present study was to examine the potential role of NK cell non-MHC-I specific inhibitory receptors expression in immune escape from HPV16(+)CIN patients. Methods The subset distribution, IFN-γ and TNF-α expression levels and immunophenotype of TIGIT, KLRG1, Siglec-7, LAIR-1, and CD300a of NK cells were investigated in peripheral blood mononuclear cell samples by flow cytometry from 82 women who were HPV16(+) with CIN grades 0, I, II–III or HPV(−) CIN 0. Immunohistochemistry was applied to detect the expression of ligands for NK receptors in the cervical tissues. HPV types were identified by PCR assays. Results The HPV16(+) subjects with high-grade lesions had an increased number of circulating peripheral blood CD56 bright NK cells with reduced functionality and IFN-γ secretion. The expression levels of the inhibitory molecules TIGIT and KLRG1 on CD56 bright NK cells increased in parallel with increasing CIN grade. In addition, TIGIT and KLRG1 related ligands, Poliovirus receptor (PVR), N-Cadherin and E-Cadherin expression level was also elevated with increasing CIN grade. Conclusions Our results suggest that up-regulation of the inhibitory TIGIT, KLRG1 and their ligands may negatively regulate cervical CD56 bright NK-mediated immunity to HPV16 and contribute to the progression of CIN. These results may facilitate the development of early-warning immune predictors and therapeutic strategies for HPV16(+) CIN based on the TIGIT and KLRG1 inhibitory pathways of NK cells.

Age-related distribution of human papillomavirus genotypes in women with cervical squamous cell carcinoma from Linyi, China, 2015–2023

Understanding the regional HPV genotype profile is critical for informing targeted vaccination strategies and optimizing cervical cancer screening programs to enhance their effectiveness. This study investigated the prevalence and distribution of human papillomavirus (HPV) genotypes among women with cervical squamous cell carcinoma (CSCC) in Linyi city, China, from 2015 to 2023. Data were obtained from 606 women histologically diagnosed with CSCC at Linyi Cancer Hospital between January 2015 and December 2023. DNA was extracted from paraffin-embedded tissue samples. HPV genotyping was performed via gene chip-based polymerase chain reaction (PCR) technology. Temporal trends and age-specific variations in HPV genotype distribution were analyzed to provide a comprehensive epidemiological assessment. The overall prevalence of HPV infection was 94.7% among 606 women with CSCC. HPV 16 was the most prevalent genotype (80.5%), followed by HPV 18 (5.2%), HPV 33 (2.8%), HPV 31 (1.8%), and HPV 58 (1.8%). Single infections were predominant (95.5%), while coinfections were observed in 4.5% of the cases. Age-specific analysis revealed that non-HPV 16 infections were more prevalent in women aged > 45 years, with greater genotype diversity in older age groups. Temporal trends indicated a decline in the prevalence of younger CSCC patients (26-45 years), whereas the prevalence of older women significantly increased. Our study revealed that HPV genotype diversity in CSCC patients varies with age, highlighting the need for age-stratified and personalized cervical cancer prevention strategies. Enhanced screening efforts for older women are essential because of the greater genotypes diversity in this group. Additionally, the observed trends in HPV prevalence over time suggest that HPV vaccination has effectively reduced the incidence of CSCC in women under 45 years of age. These findings emphasize the importance of expanding vaccination coverage and optimizing screening programs to further reduce the cervical cancer burden across different age groups.

The polymorphism analysis and therapy vaccine target epitopes screening of HPV-35 E6 E7 among the threaten α-9 HPV in Sichuan area

AbstractHigh-risk human papilloma virus (HR-HPV) persistent infection is closely associated with the development of cervical cancer and squamous intraepithelial lesion (SIL).The α-9 HPVs, which is predominantly composed of HR-HPV types, account for 75% of HR-HPV infection in Sichuan. The oncoproteins E6 and E7 of HPV play a crucial role in tumor initiation and progression. Notably, HPV-35 is the only HR-HPV type within the α-9 genus that is not included in the nine-valent HPV prophylactic vaccine. Cervical cell samples obtained from Sichuan were collected for HPV detection and genotyping. Among the 406 HPV-positive samples, 31 HPV-35 were detected, 24 HPV-35 E6 and 26 E7 were successfully amplified and sequenced, five nucleotide mutations in E6 and three in E7 were detected, T232C, T434G of E6 (W78R, I145R) and C67T, G84T of E7 (H23Y, L28F) were non-synonymy mutation. PAML 4.8 server was used to detect positive selection sites of HPV-35 E6, E7, and E6 is W78R. Phyre2 were used to predict and analyze protein structures, W78R made influences on protein structure. IEDB were used to screen epitopes vaccine target for HPV-35 affection therapy, and 5 HPV-35 E6 and 3 HPV-35 E7 most potential epitopes were obtained, the most potential peptides for therapy vaccine design were 79-91YRYSVYGETLEKQ, 45-60FACYDLCIVREGQPY, 124-135RFHNIGGRWTGR of E6; 3-19GEITTLQDYVLDLEPEA, 38-47TIDGPAGQAK, 70-88VQSTHIDIRKLEDLLMGTF of E7 and W78R mainly decreased the epitopes affinity.Conclusions Amino acid substitution in the positive selection sites of HPV-35 E6 and E7 genes have been found to influence protein structure and to decrease the overall affinity of antigen epitopes. This observation aligns with the evolutionary significance of positive selection site, which may confer advantages to the virus by making infected cells more challenging for the immune system to detect, thereby enhancing HPV’s adaptability to the host environment. The polymorphism analysis of HPV-35 E6, E7 contributes to the enrichment of α-9 HPV data in Sichuan China, which is instrumental in improving the effectiveness of clinical detection. Furthermore, these findings provide a relevant theoretical foundation for the prevention and treatment of HPV-related diseases.

High-risk human papillomavirus infection and cervical cytopathology: relationship with cervical nitric oxide levels

Abstract Background Nitric oxide (NO) may contribute to the persistence of high-risk human papillomavirus (hrHPV) infection, which has been linked to the development of premalignant lesions and cervical cancer. Our study aimed to examine the relationship between cervical NO metabolite (NOx) levels, hrHPV infection, and cytopathological findings. Additionally, we assessed cervical NOx levels as a biomarker for predicting hrHPV infection and epithelial atypia. Methods The study involved 74 women who attended the Gynecology and Obstetrics outpatient clinics at Cairo University Hospitals between November 2021 and August 2022. Cervical samples were subjected to Pap testing, assessment of NOx levels by the Griess method, and detection of hrHPV DNA by real-time polymerase chain reaction. Results High-risk HPV was detected in 37.8% of women. EA was found in 17.1% of cases, with a higher percentage among hrHPV-positive than negative cases (35.7% vs. 4.3%, p = 0.001). The most prevalent hrHPV genotype was HPV 16 (89.3%). The cervical NOx level in hrHPV-positive cases was significantly higher (37.4 µmol/mL, IQR: 34.5–45.8) compared to negative cases (2.3 µmol/mL, IQR: 1.2–9.8) (p = < 0.001). Patients with high-grade atypia showed significantly higher NOx levels (38.0 µmol/mL, IQR: 24.6–94.7) in comparison to NILM and low-grade atypia cases (5.0 µmol/mL, IQR: 1.6–33.3 and 34.5 µmol/mL, IQR: 11.7–61.7, respectively) (p = 0.006). Although the NOx levels among hrHPV-positive cases with low-grade atypia (40.4 µmol/mL, IQR: 33.3‒61.8) were higher than those with NILM (36.2 µmol/mL, IQR: 35.7‒44.0) and high-grade atypia (38.0 µmol/mL, IQR: 24.6‒94.7), the difference was not significant (p = 0.771). ROC curve analysis indicated that the cervical NOx cut-off values of > 23.61 µmol/mL and > 11.35 µmol/mL exhibited good diagnostic accuracy for the prediction of hrHPV infection and EA, respectively. Conclusions The high prevalence of hrHPV infection, particularly HPV 16, in our hospital warrants targeted treatment and comprehensive screening. Elevated cervical NOx levels are associated with hrHPV infection and high-grade atypia, suggesting their potential use as biomarkers for predicting the presence of hrHPV and abnormal cytological changes.

Investigating the link between HPV genotypes and cervical abnormality incidence in women with HPV infections: insights from a leading referral centre

Cervical cancer (CC) is a serious health issue, especially in low- and middle-income countries, primarily caused by human papillomavirus (HPV) infection, particularly genotypes 16 and 18. Other risk factors include smoking, early sexual activity, and long-term oral contraceptive use. Early detection through cervical cytology and HPV testing is vital for effective prevention. This study aimed to analyze the clinical and epidemiological characteristics of cervical intraepithelial neoplasia (CIN) in HPV-positive women at a Tehran teaching hospital, focusing on HPV genotypes and their association with CIN. We conducted a cross-sectional study of HPV-positive women who underwent Pap smear testing, HPV genotyping via real-time PCR, and colposcopy with biopsies of suspected lesions. Risk factors like smoking and alcohol consumption were evaluated, and statistical analyses were performed, including ordinal logistic regression. Among participants, 52.4% had abnormal CIN: CIN I (31.1%), CIN II (11.4%), and CIN III (10.0%). HPV-16 was the most prevalent genotype (43.7%), significantly associated with severe CIN outcomes (odds ratio [OR] = 2.88, 95% CI), followed by HPV-18 (OR = 1.87, 95% CI). Smoking increased the risk of severe CIN (OR = 1.53, 95% CI), while older age and later age at sexual debut correlated with better CIN outcomes. HPV-16 and smoking are major predictors of severe CIN, highlighting the need for targeted interventions such as HPV vaccination and smoking cessation, along with regular screenings to lower cervical cancer risks. Additional research is required to evaluate the persistence of different HPV genotypes and their progression to CIN and cervical cancer."

HPV genotype distribution and cervical lesion severity in HPV-positive women: a study from the Guizhou Province cervical cancer screening program

To analyze the infection status and subtype distribution of high-risk human papillomavirus (hrHPV) and their relationship with cervical lesions among women undergoing cervical cancer screening in Guizhou Province, thereby informing HPV vaccine selection and optimizing cervical cancer screening strategies. Data were sourced from the 2024 Guizhou Province free cervical cancer screening program for women. The prevalence of hrHPV-positive samples was analyzed, and age-specific associations between HPV genotypes and severe lesions were explored. Furthermore, the co-infection propensity for any two HPV genotypes was assessed by calculating the infection rate ratio. The overall hrHPV infection rate in the Guizhou region of China was 10.09%. Among hrHPV-positive individuals, the detection rate of cervical lesions was 11.49%. In hrHPV-positive women with cervical lesions, the most common genotypes were HPV16, 52, and 58. HPV16 was predominant across the entire spectrum of cervical lesions, and its prevalence increased significantly with the severity of cervical lesions, from 21.7% in LSIL to 39.4% in HSIL, and to 56.7% in cervical cancer (p < 0.001). However, the primary HPV types leading to cervical cancer were HPV16, 18, and 33. The infection pattern was predominantly single genotype (71.8%), with multiple genotypes accounting for only 28.2%. Among multiple infections, dual infection was the most common. The most frequent mixed genotype combinations were HPV16 + 52, 52 + 58, and 16 + 58. Significant co-infection preferences were observed for HPV16 with 33, HPV16 with 58, and HPV18 with 59. Analysis of the association between HPV genotype risk grouping and age across different cervical lesion grades showed that in the LSIL group, women aged 55-65 had a significantly 24% higher risk of HPV16 infection compared to those aged 35-45 (P = 0.023), while the risk of 'Other hrHPV' infection was significantly reduced by 8% (P = 0.019). In the HSIL group, the 45-55 age group had a significantly 11% lower risk of 'Other hrHPV' infection compared to the 35-45 age group. HPV16 predominates across the entire cervical lesion spectrum, with its prevalence significantly increasing with lesion severity. Furthermore, the nonavalent HPV vaccine covers all prevalent oncogenic hrHPV genotypes in this region (except for HPV56). These findings provide crucial epidemiological evidence for optimizing HPV vaccination strategies and cervical cancer screening programs.

Prevalence of cervicovaginal human papillomavirus infection and genotype distribution in Shanghai, China

AbstractBackgroundThe evaluation of human papillomavirus (HPV) prevalence rate dynamics and genotype distribution could support the adoption of more targeted prevention and treatment of cervical cancer. We aimed to assess the infection status and genotype characteristics of HPV among gynecological outpatients in Shanghai, China.MethodsClinical specimens were collected from patients attending gynaecological department of the Putuo Hospital, Shanghai University of Traditional Chinese Medicine, between January 2015 and December 2019. The cervicovaginal infection of 17 high-risk genotypes and 10 low-risk genotypes were analyzed by Luminex-based multiple assays.ResultsThe overall HPV infection rate was 18.81% (95% CI 18.31–19.30%) in Shanghai city, with high-risk, low-risk and mixed high- and low-risk HPV prevalence being 11.65% (95% CI 11.24–12.06%), 4.19% (95% CI 3.94–4.44%) and 2.96% (95% CI 2.74–3.17%), respectively. The five most prevalent high-risk genotypes were HPV-52 (2.95%), HPV-16 (2.34%), HPV-58 (2.07%), HPV-53 (1.67%) and HPV-39 (1.36%). The most common low-risk genotype was HPV-61 (1.52%), followed by HPV-6 (1.29%) and HPV-81 (1.19%). Moreover, the coverage of HPV genotype by nonavalent vaccine was 10.42%, and non-vaccine-covered high-risk genotype was 7.70%. The 15–24 years age group demonstrated the highest HPV prevalence (43.14%), and significant differences were observed among different age groups (P &lt; 0.001).ConclusionsThis study revealed the HPV prevalence and genotype distribution among women in Shanghai city, which could serve as guidance for HPV vaccination and preventative strategies against cervical cancer in this area.

Association between common vaginal and HPV infections and results of cytology test in the Zhoupu District, Shanghai City, China, from 2014 to 2019

Abstract Background HPV (human papillomavirus) is an important cause of cervical cancer. Cervical-vaginal infection with pathogens, such as herpes simplex virus (HSV), bacterial vaginosis Trichomonas vaginalis and vaginal candidiasis could be a cofactor. This study aimed to assess the relationship between vaginal infection with HPV genotype and cytology test results and analyze the relationship between vaginal and HPV infections and cervical cancer. Methods We performed a district-based study to elucidate the relationship among the vaginal and HPV infections and cervical cancer. We collected the cervical exfoliation data of 23,724 women admitted to the Shanghai Zhoupu Hospital and received ThinPrep cytology test (TCT) and HPV detection between 2014 and 2019. Results Total vaginal infection rate was 5.3%, and the HPV-positive group had a slightly higher vaginal infection rate than the HPV-negative group (P &lt; 0.01). The incidence rate of cervical intraepithelial neoplasia or cervical cancer with vaginal infection was higher than without vaginal infection (P &lt; 0.001). Conclusion HPV/vaginal infection-positive women tended to have abnormal results of TCT. Women with vaginal infection were more likely to develop HPV infection. HSV combined with HPV infection was noted as a causal factor for HSIL.

Activating transcription factor 3 induces oxidative stress and genotoxicity, transcriptionally modulating metastasis-related gene expression in human papillomavirus-infected cervical cancer

Activating Transcription Factor 3 (ATF3) is known for its tumor-suppressive properties in cervical cancer, particularly through its role in stress response and interactions with human papillomavirus (HPV) oncogenes. This study investigates ATF3's regulatory impact on metastasis-related genes, oxidative stress, and DNA damage in HPV-positive cervical cancer cells. HeLa and Ca Ski cell lines were transfected with ATF3-expressing vectors. Western blotting and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to confirm ATF3 overexpression following transfection. ROS assays and Comet assays assessed the impact of ATF3 on oxidative stress and DNA damage, while RT-qPCR was used to evaluate changes in HPV E6/E7, SHARP1, and MMP1 gene expression. ATF3 overexpression led to elevated ROS levels (p < 0.02), resulting in oxidative DNA damage. These results demonstrate ATF3's cytotoxic impact on cervical cancer cells through oxidative stress and DNA damage. Additionally, ATF3 overexpression significantly decreased MMP1 expression (p < 0.03), indicating a potential anti-metastatic effect, while SHARP1 and HPV E6/E7 expression levels were not significantly altered, indicating selective gene modulation by ATF3. These findings reveal that ATF3 contributes to tumor suppression in cervical cancer by modulating oxidative stress and DNA damage, selectively targeting genes involved in metastasis. These findings supports ATF3's role in regulating key pathways in HPV-positive cervical cancer cells, providing a basis for further exploration of ATF3 as a target in therapeutic strategies aimed at improving outcomes in cervical cancer.

Evaluation of the SureX HPV genotyping test for the detection of high-risk HPV in cervical cancer screening

Abstract Background The SureX HPV genotyping test (SureX HPV test), which targets the human papillomavirus (HPV) E6/E7 genes was compared with the Cobas 4800 and Venus HPV tests for detecting 14 high-risk HPV (HR-HPV) types in clinical referral and follow-up patients to evaluate its value for cervical cancer screening. Methods Two different populations were enrolled in the study. The first population comprised 185 cases and was used for comparing the SureX HPV test (Health, China) with the Cobas 4800 test (Roche, USA). The second population comprised 290 cases and was used for comparing the SureX HPV test (Health, China) with the Venus HPV test (Zhijiang, China). Polymerase chain reaction (PCR) sequencing was performed for further confirmation of discordant results. Results In the first population, the overall agreement rate was 95.6% for 14 high-risk HPV types. Eight discordant cases were confirmed by PCR sequencing, which showed that the agreement rates were 75.0% between the SureX HPV test and PCR sequencing and 25.0% between the Cobas 4800 test and PCR sequencing ( P  &lt; 0.01). In the second population, the overall agreement rate was 95.5%. Thirteen discordant cases were confirmed by PCR sequencing, which showed that the agreement rates were 76.9% between the SureX HPV test and PCR sequencing and 23.1% between the Venus HPV test and PCR sequencing ( P  &lt; 0.01). With cervical intraepithelial neoplasia grade 2+ (CIN2+) as the reference standard, the sensitivity values of the SureX HPV test and the Venus HPV test were 93.5% and 92.0%, ( P  &gt; 0.05), while the specificity values were 43.3% and 46.7%, respectively ( P  &gt; 0.05). Conclusion The SureX HPV test had good consistency with both the Cobas 4800 and Venus HPV tests for 14 HR-HPV types. In addition, it avoided some false negatives and false positives. Therefore, the SureX HPV test can be used for cervical cancer screening.

Genetic variability, phylogeny and functional implication of the long control region in human papillomavirus type 16, 18 and 58 in Chengdu, China

Abstract Background Long control region (LCR) of human papillomavirus (HPV) has shown multiple functions on regulating viral transcription. The variations of LCR related to different lineages/sub-lineages have been found to affect viral persistence and cervical cancer progression differently. In this study, we focused on gene polymorphism of HPV16/18/58 LCR to assess the effect variations caused on transcription factor binding sites (TFBS) and provided more data for further study of LCR in Southwest China. Methods LCR of HPV16/18/58 were amplified and sequenced to do polymorphic and phylogenetic anlysis. Sequences of each type were aligned with the reference sequence by MEGA 6.0 to identify SNPs. Neighbor-joining phylogenetic trees were constructed using MEGA 6.0. Transcription factor binding sites were predicted by JASPAR database. Results The prevalence of these three HPVs ranked as HPV16 (12.8%) &gt; HPV58 (12.6%) &gt; HPV18 (3.5%) in Chengdu, Southwest China. 59 SNPs were identified in HPV16-LCR, 18 of them were novel mutations. 30 SNP were found in HPV18-LCR, 8 of them were novel. 55 SNPs were detected in HPV58-LCR, 18 of them were novel. Also, an insertion (CTTGTCAGTTTC) was detected in HPV58-LCR between position 7279 and 7280. As shown in the neighbor-joining phylogenetic trees, most isolates of HPV16/18/58 were clustered into lineage A. In addition, one isolate of HPV16 was classified into lineage C and 3 isolates of HPV58 were classified as lineage B. JASPAR results suggested that TFBS were potentially influenced by 7/6 mutations on LCR of HPV16/18. The insertion and 5 mutations were shown effects in LCR of HPV58. Conclusion This study provides more data for understanding the relation among LCR mutations, lineages and carcinogenesis. It also helps performing further study to demonstrate biological function of LCR and find potential marker for diagnosis and therapy.

The genetic variability, phylogeny and functional significance of E6, E7 and LCR in human papillomavirus type 52 isolates in Sichuan, China

Abstract Background Variations in human papillomavirus (HPV) E6 and E7 have been shown to be closely related to the persistence of the virus and the occurrence and development of cervical cancer. Long control region (LCR) of HPV has been shown multiple functions on regulating viral transcription. In recent years, there have been reports on E6/E7/LCR of HPV-16 and HPV-58, but there are few studies on HPV-52, especially for LCR. In this study, we focused on gene polymorphism of the HPV-52 E6/E7/LCR sequences, assessed the effects of variations on the immune recognition of viral E6 and E7 antigens, predicted the effect of LCR variations on transcription factor binding sites and provided more basic date for further study of E6/E7/LCR in Chengdu, China. Methods LCR/E6/E7 of the HPV-52 were amplified and sequenced to do polymorphic and phylogenetic analysis. Sequences were aligned with the reference sequence by MEGA 7.0 to identify SNP. A neighbor-joining phylogenetic tree was constructed by MEGA 7.0, followed by the secondary structure prediction of the related proteins using PSIPRED 4.0. The selection pressure of E6 and E7 coding regions were estimated by Bayes empirical Bayes analysis of PAML 4.9. The HLA class-I and II binding peptides were predicted by the Immune Epitope Database server. The B cell epitopes were predicted by ABCpred server. Transcription factor binding sites in LCR were predicted by JASPAR database. Results 50 SNP sites (6 in E6, 10 in E7, 34 in LCR) were found. From the most variable to the least variable, the nucleotide variations were LCR &gt; E7 &gt; E6. Two deletions were found between the nucleotide sites 7387–7391 (TTATG) and 7698–7700 (CTT) in all samples. A deletion was found between the nucleotide sites 7287–7288 (TG) in 97.56% (40/41) of the samples. The combinations of all the SNP sites and deletions resulted in 12 unique sequences. As shown in the neighbor-joining phylogenetic tree, except for one belonging to sub-lineage C2, others sequences clustered into sub-lineage B2. No positive selection was observed in E6 and E7. 8 non-synonymous amino acid substitutions (including E3Q and K93R in the E6, and T37I, S52D, Y59D, H61Y, D64N and L99R in the E7) were potential affecting multiple putative epitopes for both CD4+ and CD8+ T-cells and B-cells. A7168G was the most variable site (100%) and the binding sites for transcription factor VAX1 in LCR. In addition, the prediction results showed that LCR had the high probability binding sites for transcription factors SOX9, FOS, RAX, HOXA5, VAX1 and SRY. Conclusion This study provides basic data for understanding the relation among E6/E7/LCR mutations, lineages and carcinogenesis. Furthermore, it provides an insight into the intrinsic geographical relatedness and biological differences of the HPV-52 variants, and contributes to further research on the HPV-52 therapeutic vaccine development.

Genetic variability in HPV 33 and 35 E6 and E7 genes from South African and Mozambican women with different cervical cytology status

Abstract Background Among the high-risk human Papillomavirus (hr-HPV) genotypes related to cervical cancer (CC) cases, HPV16 and 18 are the most studied worldwide. However, several studies have identified HPV 33 and HPV 35 as some of the most common genotypes in sub-Saharan African regions. This study aims to investigate the genetic variability and lineages of HPV 33 and 35 based on the HPV E6 and E7 genes in isolates from South African and Mozambican women with different cervical cytology statuses. Methods The study analysed 26 HPV 33 and 46 HPV 35 DNA samples collected previously from South African and Mozambican women. The E6 and E7 genes were amplified by polymerase chain reaction (PCR) using genotype-specific primers. Sequences were mapped to the reference sequences using Qiagen CLC Genomics Workbench software and aligned with the HPV 33 and 35 lineages reference sequences. Single nucleotide polymorphisms (SNPs) in the E6 and E7 genes were identified, and the phylogenetic trees were generated. Results Of the 26 HPV 33-positive subjects, 62% (16/26) were from women with high-grade squamous intraepithelial lesions (HSILs). Phylogenetic analysis revealed that 38% (10/26) of the isolates clustered with European lineages. Specifically, 30% (8/26) of isolates clustered in the A1 sublineage, and 8% (2/26) in the A2 sublineage. The African 1 lineage (B1 sublineage) was identified in 19% (5/26) of the isolates. Notably, 42% (11/26) of the isolates did not cluster with any of the reference sequences under investigation, through E6 and E7 genes analysis. In the HPV 33 E6 gene, 80 SNPs were identified and 30 in the E7, frequently in the HSILs subjects. Of the 46 HPV35-positive subjects, 46% (21/46) were from women with HSILs, and 43% (20/46) of the isolates clustered with the European lineages. Specifically, 39% (18/46) clustered to the A1 sublineage, and 4% (2/46) clustered to the A2 sublineage. However, 4% (2/46) of the isolates did not cluster with any of the study sublineage. Seven SNPs were detected in the E6 region and two in the E7 region of the HPV 35 isolates. Conclusion The present study’s genetic analysis showed a higher prevalence of European HPV 33 and 35 variants. Fewer SNPs were found in the studied genes of HPV 35 isolates. The addition of HPV 35 to the HPV vaccines would result in improved cervical cancer prevention. The study findings contribute to a better understanding of the genetic diversity of the HPV circulating in Southern African women and may inform strategies for cervical cancer prevention, including the design of therapeutic vaccines for women in advanced cytological disease stages.

High-risk human papillomavirus detection in self-collected vaginal samples compared with healthcare worker collected cervical samples among women attending gynecology clinics at a tertiary hospital in Pretoria, South Africa

Abstract Background In 2017, the South African National Department of Health (NDoH) Cervical Cancer Prevention and Control Policy was revised. Human papillomavirus (HPV) testing on self-collected samples may offer improved screening uptake. The objectives of the study were to compare the positivity of high-risk (hr)-HPV deoxyribonucleic acid (DNA) and hrHPV viral messenger ribonucleic acid (mRNA) between healthcare worker-collected cervical and self-collected vaginal samples and investigate the accuracy of the applicator-tampon-based self-collected samples in detecting hrHPV DNA and hrHPV mRNA. Methods A total of 527 women aged 18 years and older and seeking gynecology services at a tertiary hospital in Pretoria, South Africa, were enrolled. Vaginal samples were self-collected using SelfCerv applicator tampon, followed by cervical samples collected by a healthcare worker using a Cervex Brush® Combi. Both samples were tested with the Abbott m2000 analyzer for 14-hrHPV types and 285 paired samples were tested for hrHPV E6/E7 mRNA using the Aptima HR-HPV mRNA assay. The prevalence of hrHPV DNA and hrHPV E6/E7 mRNA was estimated and the positivity between the two collection methods was compared for the total group as well as per age group. Results HrHPV prevalence was 48.0% (95% CI 43.7–52.4) among healthcare worker collected samples and 47.6% (95% CI 43.3–52.0) among self-collected samples. There was no difference in positivity between healthcare worker collection (48.0%) and applicator-tampon-based self-collection, 47.6% (p-value = 0.90). The proportions of hrHPV were equal between the age groups as shown by the McNemar test (p = 0.9036) results for correlated proportions. The prevalence of hrHPV mRNA was 78.6% (95% CI 73.4–83.2) and 58.6% (95% CI 52.6–64.4) for healthcare worker- and self-collection, respectively. The McNemar test for correlated proportions was highly significant (p &lt; 0.0001), indicating that the hrHPV mRNA proportions are not comparable, although this differed between age groups. Conclusions Applicator-tampon-based self-collection has a comparable hrHPV DNA positivity rate as healthcare worker collection but different positivity rates for hrHPV mRNA. Self-sampling showed high concordance with healthcare worker-collected sampling for hrHPV DNA detection, especially regarding HPV 16/18 detection. HrHPV DNA was equally detected between the total group as well as per age group. Implementation of self-sampling using an applicator tampon as a primary screening tool may be considered.

The polymorphism analysis and epitope predicted of Alphapapillomavirus 9 E6 in Sichuan, China

Abstract Background The Alphapapillomavirus 9 (α-9 HPV) is a member of the Alphapapillomavirus genus and Papillomaviridae family. These viruses are almost all carcinogenic HPV, which is closely related to 75% of invasive cervical cancer worldwide, and has a high prevalence in Sichuan. The carcinogenic function is mainly realized by its E6 oncoprotein. Methods Cell samples were collected by cervical scraped for HPV detecting and typing. HPV-16, HPV-31, HPV-33, HPV-52, HPV-58 5 α-9 genus HPV subtype positive samples were selected, their E6 gene was sequenced and analyzed. The positive selection sites of HPV E6 genes were estimated by PAML 4.8 server. The secondary and tertiary structure of E6 protein were predicted by PSIPred and Swiss-model. The T-cell antigen epitopes of E6 protein were predicted by IEDB. Results α-9 HPV has a high prevalence in Sichuan, China. From 2012 to 2017, 18,067 cell cervical samples were collected, and 3135 were detected with α-9 HPV infection. Among which, 250 cases HPV-16 E6, 96 cases HPV-31 E6, 216 cases HPV-33 E6, 288 cases HPV-52 E6 and 405 cases HPV-58 E6 were successfully amplified, 17, 6, 6, 13, and 4 non-synonymous nucleotide mutations were respectively detected in HPV-16, 31, 33, 52, and 58 E6, 7 positive selection sites of α-9 HPV E6 were selected out (D32E of HPV-16 E6, K35N, K93N and R145I of HPV-33 E6, K93R of HPV-52 E6, K93N and R145K of HPV-58 E6). The structure and antigen epitopes of E6 protein with amino acid substitution differ from those of wild-type E6 protein, especially for the mutation located in the E6 positive selection site. Conclusions HPV E6 nucleotide non-synonymous mutation in the positive selection site influence the protein structure and decrease the antigen epitopes affinity of the E6 protein overall, making it more difficult for the HPV-infected cells to be detected by the immune system, and enhancing the HPV adaptability to the environment. Mutations influence the validity of HPV clinical diagnostic probes, the polymorphism analysis of α-9 HPV E6 enrich the data of HR-risk HPV in Sichuan China, and the detection probes designed with the polymorphism data in mind can improve the efficiency of clinical detection; Mutations influence epitopes affinity, the association of E6 polymorphism and epitope affinity can improve the design of therapeutic vaccine with good immunity and high generality antigen epitope; The above study all provide a good theoretical basis for the prevention and treatment of HPV-related diseases.

Distribution of cervical lesions in high-risk HPV (hr-HPV) positive women with ASC-US: a retrospective single-center study in China

Abstract Background To investigate distributions of cervical lesions and factors associated with the severity of the cervical lesions in high-risk HPV (hr-HPV) positive women with atypical squamous cells of undetermined significance (ASC-US) cytology. Methods Clinical information of 250,000 women who underwent HPV and cytological test was collected from January 2012 to January 2019. The association between the severity of the cervical lesions and hr-HPV genotypes, hr-HPV viral load, and ages, were analyzed in hr-HPV-positive/ASC-US women. Results 3459 hr-HPV-positive/ASC-US women were enrolled in this study. Overall, 43.51% of women with ASC-US had normal histological results, 34.35% had high-grade squamous intraepithelial lesion (HSIL), and 1.30% had cervical cancer. The rate of HSIL or worse (HSIL+) in women with single HPV16 infection (63.09%) was the highest, followed by HPV33 (57.50%), HPV51 (36.11%), HPV58 (36.11%), HPV52 (28.28%), HPV18 (26.37%), HPV66 (19.35%), HPV39 (18.92%), HPV53 (15.00%), and HPV56 (8.51%). Detection rate of HSIL+ in low, intermediate and high viral-load groups were 15.87% (n = 30), 34.91% (n = 74) and 40.68% (n = 214) (Cochran-Armitage Trend test χ 2  = 35.03, p  &lt; 0.0001). Compared with the 51–60-year-old group (21.65%), the women in ≤ 30 (40.52%), 31–40 (39.67%), and 41–50 (34.22%) year-old groups had significantly higher risk of HSIL+. The women in ≤ 51–60 (2.68%) and &gt; 60 (3.41%) year-old groups were at increased risk for cervical cancer, compared with the ≤ 30-year-old group (0.61%). Conclusions ASC-US women with HPV 16/18/33/51/52/58 single infection and multiple infections, as well as high HPV viral loads, have high risk of HSIL+.

Prognostic assessment of cervical cancer based on biomarkers: the interaction of ERRα and immune microenvironment

Cervical cancer poses a substantial global health challenge. Estrogen-related receptor alpha (ERRα) is a central regulator of cellular energy metabolism associated with poor cancer prognosis. However, the effect of ERRα expression on cervical cancer prognosis and immune infiltration has not been explored. This study aims to clarify the expression pattern and role of ERRα in cervical cancer. We analyzed ERRα expression and its clinical prognosis in cervical cancer using multiple databases, including The Cancer Genome Atlas (TCGA) and Tumor Immune Estimation Resource (TIMER). The results were further validated through immunohistochemistry (IHC) on 221 cervical cancer tissue samples. Furthermore, Kaplan-Meier and Cox regression analyses were used to assess the clinical significance of ERRα in cervical cancer patients. All calculations were performed using the R package. ERRα expression was significantly higher in cervical cancer tissues compared to normal tissues. High ERRα expression was associated with poor overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS). Multivariate Cox regression analysis confirmed ERRα as an independent prognostic factor. Additionally, ERRα expression correlated with various immune cell types and immune checkpoints, indicating its role in the tumor immune microenvironment. ERRα emerges as a promising prognostic biomarker in cervical cancer, influencing immune cell infiltration and potentially guiding personalized therapeutic approaches. Future investigations are warranted to delineate the mechanistic pathways through which ERRα contributes to cervical cancer progression and to assess its viability as a target for innovative immunotherapy strategies.

Differential expression of human papillomavirus 16-, 18-, 52-, and 58-derived transcripts in cervical intraepithelial neoplasia

Abstract Background Human papillomavirus (HPV) infection is a primary cause of cervical cancer. Although epidemiologic study revealed that carcinogenic risk differs according to HPV genotypes, the expression patterns of HPV-derived transcripts and their dependence on HPV genotypes have not yet been fully elucidated. Methods In this study, 382 patients with abnormal cervical cytology were enrolled to assess the associations between HPV-derived transcripts and cervical intraepithelial neoplasia (CIN) grades and/or HPV genotypes. Specifically, four HPV-derived transcripts, namely, oncogenes E6 and E6* , E1^E4 , and viral capsid protein L1 in four major HPV genotypes—HPV 16, 18, 52, and 58—were investigated. Results The detection rate of E6/E6* increased with CIN progression, whereas there was no significant change in the detection rate of E1^E4 or L1 among CIN grades. In addition, we found that L1 gene expression was HPV type-dependent. Almost all HPV 52-positive specimens, approximately 50% of HPV 58-positive specimens, around 33% of HPV 16-positive specimens, and only one HPV18-positive specimen expressed L1 . Conclusions We demonstrated that HPV-derived transcripts are HPV genotype-dependent. Especially, expression patterns of L1 gene expression might reflect HPV genotype-dependent patterns of carcinogenesis.

Improvement in RNA quantity and quality in cervico-vaginal cytology

AbstractThe separation of exfoliated cells from the brushes used during cervico-vaginal smears is difficult, a problem which may affect the quality of ribonucleic acid (RNA) extracted. We compared the results of RNA extraction from cervico-vaginal cytology samples according to the type of tubes, preservative solutions, and storage temperature. The samples included exfoliated cervico-vaginal cytological specimens from patients with human papilloma virus 16, positive for cervical intraepithelial neoplasia or cervical cancer. Exfoliated cells were obtained by shaking a brush in a conventional rigid vial tube or squeezing the brush in a soft vial tube. RNA quantity and quality were compared between the two tubes. The concentration and purity of RNA (A260/A280 and A260/A230 ratios) was compared amongst five groups: Group 1, standard frozen storage; Group 2–4, RNA stabilization reagents with room temperature [RNAlater RNA Stabilization Reagent, RNAprotect cell Reagent and AllProtect Tissue Reagent]; and Group 5, Surepath Preservative fluid. To demonstrate the utility of the extracted RNA for PCR-based cDNA synthesis, GAPDH and E6 were targeted and gel band densities of GAPDH and E6 were measured. The median RNA concentration was significantly higher in the soft tubes compared with the rigid tubes (100.2 vs. 7.1 ng/μL, p = 0.0209). The purity of the RNA was higher in soft vial tubes than in rigid vials, as measured by A260/280 and A260/230 ratios. The RNA concentration, purity, and GAPDH density of groups 1, 2 and 3 were significantly higher than those of groups 4 and 5. Moreover, E6 density of group 1 and 2 was significantly higher than that of group 3, 4 and 5. The use of soft tubes enhanced the mRNA quantity and quality in cervico-vaginal cytology. The products of mRNA extraction using RNAlater RNA Stabilization Reagent and RNAprotect Cell Reagent at room temperature were comparable to those obtained by conventional frozen storage. Our protocol improved the yield and quality of RNA and might produce better results for molecular analysis in cervico-vaginal cytology.

Genetic variations and carcinogenicity analysis of E6/E7 oncogenes in HPV31 and HPV35 in Taizhou, China

The purpose of this study was to investigate the genetic variations in the E6 and E7 oncogenes of HPV31 and HPV35, and to explore their potential role in cervical cancer risk among women in Taizhou, China. Cervical exfoliated cells were collected for HPV genotyping, and only patients with a single infection of either HPV31 or HPV35 were selected for this study. The ABI 3730xl sequencer was utilized to sequence the E6 and E7 genes, followed by subsequent sequence alignment, analysis of genetic heterogeneity, and construction of maximum likelihood phylogenetic trees for the sequences of HPV31 and HPV35 using BioEdit and MEGA softwares. From 2013 to 2023, 148 HPV31 E6/E7 gene sequences and 121 HPV35 E6/E7 gene sequences were successfully obtained. We identified 16 distinct HPV31 E6/E7 variants and 5 distinct HPV35 E6/E7 variants, which have been deposited in GenBank under accession numbers OR540563-OR540578 and OR540579-OR540583, respectively. Phylogenetic analysis revealed that most of the HPV31 variants belonged to sublineage A2 (57.4%), followed by sublineages C2 (26.4%), C3 (14.2%) and B1 (2.0%). The proportion of CIN2 + patients in sublineage A2 was greater than that in other HPV31 sublineages, but the difference was not statistically significant (69.2% vs. 30.8%, P > 0.05). The most common variant in A2 was 31CNTZ07, which has a greater risk of CIN2 + than other A2 variants (OR = 3.5, 95% CI = 1.31 to 9.36; P < 0.05). In addition, all the HPV35 variants belonged to lineage A, of which 99.2% belonged to sublineage A1. 35CNTZ01 and 35CNTZ03 were the two most common HPV35 variants in our population, but no significant difference in their carcinogenic ability was observed (P < 0.05). These data provides a deeper insight into the distribution of geographic/ethnical HPV31 and HPV35 variants, which contribute to the development of multivalent HPV vaccines and diagnostic assays that are suitable for Chinese women.

The R2TP complex stabilises E7 to drive human papillomavirus-mediated pathogenesis in cellular models of cervical cancer

Human papillomaviruses (HPVs), particularly types 16 and 18, are major contributors to cervical cancer through the oncogenic activities of the E6 and E7 proteins. These viral proteins inactivate the tumour suppressors p53 and pRB, driving uncontrolled cellular proliferation. In this study, we investigated the interaction between the HPV E7 protein and the R2TP complex, a co-chaperone involved in essential cellular functions, including ribosome biogenesis, transcription, and macromolecular assembly. We identified PIH1D1, a core R2TP subunit, as an interacting partner of HPV16 and HPV18 E7 proteins. Mutagenesis and pull-down assays showed that phosphorylation of HPV E7 by casein kinase 2 (CK2) is critical for this interaction, as mutations of serine residues within the CK2 phospho-acceptor site on E7 disrupted the binding with PIH1D1. Furthermore, PIH1D1 facilitated the association of E7 with the retinoblastoma protein (pRB), forming a complex that likely promotes cancer cell proliferation. Immunohistochemical analysis of cervical cancer tissues revealed overexpression of PIH1D1, RUVBL1, and RPAP3-key components of the R2TP complex. Functional assays confirmed that PIH1D1 is crucial for cervical cancer cell growth and migration, as its silencing reduced E7 stability and impaired proliferation. Collectively, these findings highlight that PIH1D1, and by extension, the R2TP complex, is integral to the HPV-driven malignancy and suggest potential as therapeutic targets in HPV-related cancers. IMPORTANCE: Despite being largely preventable through vaccination, cervical cancer is a significant concern for public health. Research is essential to understand the factors contributing to its high incidence and mortality and to devise effective prevention and treatment strategies. We investigated the functional role of PIH1D1, a core subunit of the R2TP complex, in the HPV-mediated cervical carcinogenesis. The interaction of the R2TP complex, HPV E7, and the tumour suppressor pRB proteins may be essential in driving malignant transformation.

Design and computational evaluation of a prophylactic and therapeutic multi-epitope vaccine candidate against cervical cancer

Cervical cancer is the fourth most common cancer among women worldwide, caused by the human papillomavirus (HPV). HPV16 /18 are strongly associated with the development of cervical cancer. HPV vaccines are not widely available in economically underdeveloped areas. They also have limited efficacy against pre-existing HPV infections and cervical lesions. Therefore, the study aims to computationally design a vaccine that induces both prophylactic and therapeutic immunity against cervical cancer. Using computational approaches, we designed a multi-epitope vaccine incorporating 62 cytotoxic T lymphocyte (CTL) epitopes, 7 helper T lymphocyte (HTL) epitopes, and 3 linear B-cell epitopes from conserved regions of HPV16/18 E6, E7, and L2 proteins. To increase immunogenicity, the adjuvant RS-09 (APPHALS) was added to the N-terminal of the vaccine. The chosen CTL and HTL epitopes have the potential to achieve 100% worldwide population coverage. The vaccine candidate has appropriate physicochemical properties. The vaccine's secondary and tertiary structures were predicted, followed by refinement and validation of the models. The vaccine has a high affinity for Toll-like receptor 4 (TLR4), as indicated by its molecular docking score of -1164.4 kcal/mol and RMSD fluctuation range of 17 to 22.5 angstroms (Å) at the end of the MD simulation period. Immune response simulation showed that the vaccine candidate could induce strong humoral and cellular immune responses. The vaccine sequence's GC content was calculated to be 48.99%, and subsequently, in silico cloning of the vaccine was performed in the pET28a (+) vector. The results reveal that this vaccine is highly immunogenic; however, experimental testing is required to confirm its efficacy and safety.

Factors related to cervicogenital high-risk human papillomavirus persistence among Chinese women: a nationwide multi-center cohort study

Persistent infection with high-risk human papillomavirus (HR-HPV) is a necessary cause of cervical cancer and its precancerous lesions. This study aimed to identify factors associated with HR-HPV persistence in Chinese women. This study is a population-based, nationwide, multi-center prospective cohort study initiated in 2017, and a total of 10,481 women undergoing cervical cancer screening were enrolled. A subset of 1,684 women who tested HR-HPV positive at baseline were included in the analysis. The results of their HPV testing at baseline and during three follow-up visits (2018-2020) were used to assess 1-, 2-, and 3-year HR-HPV persistence. Variables with statistically significant associations in univariate analyses, expressed as odds ratios (ORs) with 95% confidence intervals (CIs), were subsequently entered into a stepwise multivariate logistic regression model to identify independent predictors of HR-HPV persistence. The mean age of 1,684 HPV-positive women at baseline was 47.6 ± 9.5 (interquartile range (IQR) = 42-54) years. The most prevalent genotypes at baseline were HPV52 (28.3%), HPV16 (20.2%), HPV58 (17.8%), HPV33 (6.7%), and HPV18 (6.2%). Overall HR-HPV persistence rates declined over time were 66.8% at 1 year, 48.3% at 2 years, and 39.9% at 3 years. Infection with HPV33 (OR = 2.40, 95% CI: 1.42-4.01), HPV52 (OR = 1.95, 95% CI: 1.45-2.64), or HPV58 (OR = 2.01, 95% CI: 1.40-2.88), as well as postmenopausal status (OR = 2.84, 95% CI: 2.17-3.72), were significantly associated with 3-year persistence, and alcohol consumption was associated with a reduced risk of persistence (OR = 0.49, 95% CI: 0.30-0.79). Furthermore, HPV16 was the most frequently detected genotype in cervical intraepithelial neoplasia grades 2 and worse (CIN2+), indicating it plays a predominant role in chronically pathogenic of high cervical disease. These findings underscore the importance of genotype-specific and host-related factors in HR-HPV persistence and support the implementation of tailored cervical cancer screening strategies. Women infected with HPV33, HPV52, or HPV58, along with HPV16 may require closer long-term monitoring to prevent progression to high-grade cervical lesions.

The relationship between human papillomavirus genotype distribution and age and the association with high-grade squamous intraepithelial lesions of the cervix or cervical cancer in Jilin Province, China

Using a retrospective cohort of 21,282 individuals aged 10-89 years (634 males, 20,648 females) from Jilin Province between October 2017 and September 2019, we performed HPV genotyping and colposcopy-directed biopsy to delineate age- and genotype-specific infection patterns. High-risk HPV prevalence peaked in adolescence (≤ 18 years) and declined thereafter, whereas low-risk types showed modest age trends (P  37 years.

The co-regulation of HPV infection by vaginal microbiota and the immune system

Persistent high-risk human papillomavirus (HR-HPV) infection is the most critical risk factor for cervical cancer. The vaginal microbiota and the host immune status are both closely related to HPV infection. The vaginal microbiota regulates multiple immune signaling pathways. Conversely, the immune status also affects the stability of the microbiota. The two interact with each other and jointly regulate the outcome of HPV infection. Establishing a tripartite coordinated regulatory mechanism model involving the microbiota, immune system, and HPV will facilitate the development of individualized predictive models in the future, identification of precise intervention targets, and maximization of HPV clearance.

Human papillomavirus prevalence and genotype distribution among 30,147 screened women and 3,362 cervical cancer patients in China: a retrospective study

Abstract Background Persistent infection with high-risk human papillomavirus (HR-HPV) is the primary cause of cervical cancer. Understanding genotype distribution and evaluating screening strategies are essential for effective prevention. Methods We retrospectively analyzed cervical cancer screening data from 97,686 women aged 35–64 years in Nanjing (2021–2023). Among these, 30,147 underwent combined cytology and HPV testing and 67,539 TCT alone. HPV genotyping was further performed in 3,362 histologically confirmed cervical cancer cases (3,014 squamous cell carcinomas [SCC] and 348 adenocarcinomas [ADC]) from multiple regions in China. Results Combined screening achieved a significantly higher detection rate of abnormalities than TCT alone (13.70% vs. 1.79%, p &lt; 0.001). Overall HPV positivity was 11.19%, increasing with age and peaking at 16.85% in women aged 60–64. The most frequent genotypes were HPV52, HPV58, and HPV16. In cervical cancer cases, HPV was detected in 92.73% of SCC and 59.77% of ADC. The proportion of HPV-negative cancers increased with age, particularly in ADC. Conclusions Combined TCT and HPV testing improves detection of cervical lesions compared with cytology alone. The observed age-specific and histology-specific differences in HPV prevalence and genotype distribution emphasize the need for tailored screening strategies, particularly for older women. These findings provide region-specific evidence to support the refinement of cervical cancer prevention and control strategies in China, particularly in contexts with similar demographic and epidemiological characteristics to the study population.

Prevalence characteristics of human papillomavirus among women in Henan Province of China

The aim of this study is to analyze the prevalence and genotype distribution of HPV among the female populations in Henan Province, which can provide an evidence for the local governments to make develop strategies for cervical cancer prevention and vaccination. The study was designed to analyze the results of cervical swab HPV test results from female patients who visited the First Affiliated Hospital of Zhengzhou University from January 2020 to May 2023. The collected cervical specimens were processed using specialized nucleic acid extraction reagents to obtain purified nucleic acid extracts. Genotype identification was then performed via real-time fluorescence PCR technology with two commercial detection kits. The assay detects 23 HPV genotypes (17 high-risk types: 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82; and 6 low-risk types: 6, 11, 42, 43, 44, 81). The HPV prevalence was calculated using GraphPad Prism 8.0. The overall HPV prevalence was 21.31% (12,950/60,765) among the 60,765 female patients, of which the single, double, and multiple HPV infections accounted for 14.81% (9,001/60,765), 4.25% (2,584/60,765), and 2.25% (1,365/60,765) of the total cases. 17.82% (10,836/60,765) of the total samples were infected with high-risk HPV (HR-HPV), accounting for 83.67% (10,836/12,950) of the HPV positive women. The most common infection pattern is HPV single infection, accounting for 69.51% of the positive women. The top four most commonly detected types were HPV-52 (4.30% 2,612/60,765), HPV-58 (2.81% 1,710/60,765), HPV-16 (2.81% 1,709/60,765), and HPV-53 (2.25% 1,367/60,765). The positive rate of HPV among different age groups was statistically significant (p<0.05). This study provides baseline data on the epidemiological characteristics of HPV. The prevalence of HPV among women in Henan Province is high. The highest prevalence is among women less than 20 years. The predominant genotypes identified were HPV 52, 58, 16, and 53. This genotype distribution suggests that the Gardasil 9 vaccine, which covers HPV 52, 58, and 16, could potentially address a significant proportion of high-risk HPV infections in this population. The high prevalence of HPV 53, a genotype not targeted by current vaccines, warrants further investigation into its oncogenic role and epidemiological significance.

High-risk human papillomavirus (hr-HPV) prevalence and abnormal cervical cytology in rural high-altitude communities: a population-based cross-sectional study in the Southern Tibetan Plateau, China (2023–2024)

Cervical cancer prevention remains challenging in resource-limited high-altitude regions. This study investigated the prevalence of high-risk human papillomavirus (hr-HPV) and cytological abnormalities in southern Tibet, China. A population-based cross-sectional study (2023-2024) enrolled 21,112 women from the Shannan Region (altitude: 3500-6000 m). The participants underwent hr-HPV genotyping (16/18 and 16 other types) and ThinPrep cytologic testing (TCT). Statistical analyses included χ² tests and quadratic regression. The overall hr-HPV prevalence was 9.57% (2,021/21,112). Non-16/18 types predominated (83.37% of infections), with HPV16/18 accounting for 1.59% of infections. Age-stratified analysis revealed a U-shaped infection curve: peaks at 20-24 years (16.07%) and ≥ 65 years (11.84%), nadir at 45-49 years (8.94%; R²=0.89, p < 0.01). Cytological abnormalities occurred in 8.27% (1,746/21,112) of the patients, predominantly ASC-US (79.5%). The ≥ 65 years participants presented the highest abnormality rate (11.84% vs. other groups). Hr-HPV positivity correlated strongly with cytological severity (p < 0.001), increasing from NILM (7.84%) to HSIL (92.31%). HPV16/18 was more prevalent in high-grade lesions (HSIL: 38.46%; OR = 60.2 vs. NILM, 95% CI: 18.4-196.7). Shannan has a distinct hr-HPV epidemiology characterized by a lower prevalence, U-shaped age distribution, and non-16/18 type dominance. The resurgence of infections/abnormalities in elderly women warrants age-tailored screening. These findings support prioritizing multivalent vaccines in this high-altitude population.

Multiple high-risk human papillomavirus infections exacerbate cervical lesion risk: epidemiological evidence from suining, Sichuan

Studies on the pathogenicity of single and multiple human papillomavirus (HPV) infections have reported inconsistent results. Moreover, no data on HPV epidemiology in the Suining region of China have been published. Cervical samples were collected from women undergoing gynecological examinations at the Suining Central Hospital. Fluorescent polymerase chain reaction (PCR) was used for HPV genotyping, and cytological and pathological examinations were performed to analyze the correlation between the infection patterns of high-risk HPV types (single vs. multiple infections) and cervical lesions. The most prevalent high-risk HPV types were HPV52, 58, 16, 53, and 51. The proportion of disease cases (cervical intraepithelial neoplasia or cervical cancer) in multiple infection groups (720/1,550) was significantly higher than that in single infection groups (2,109/6,498) (relative risk = 1.43, 95% confidence interval = 1.34-1.53, p < 0.001). A positive correlation was observed between the number of HPV infections and the proportion of disease cases (r = 0.839, p = 0.009). Multiple HPV infections were significantly associated with more severe cervical lesions, and a higher infection multiplicity correlated with an increased pathogenic risk. Our findings support that multiple HPV infections significantly elevate cervical lesion risk, providing a basis for referring such patients to further examination.

Trends in HPV-positive cervical cancer prevalence: a retrospective study from 2013 to 2020

Cervical cancer ranks as the fourth most common cancer among women globally, mainly linked to persistent high-risk HPV infection. In China, significant challenges persist, notably the low rates of HPV vaccination and a substantial case burden. This study retrospectively examined HPV-related cervical cancer data from a tertiary hospital spanning the years 2013 to 2020, to evaluate annual and age-specific incidence trends and offer insights for prevention and treatment strategies. The retrospective analysis encompassed patients who utilized the gynecological outpatient and inpatient services at the Third Affiliated Hospital of Sun Yat-sen University from 2013 to 2020. HPV genotyping, covering 21 subtypes, was conducted using hybrid capture-based assays. The assessment of cervical biopsy disease etiology was performed by a senior pathologist. During the study period, a total of 9,194 cases of HPV-positive individuals were identified, among which 479 cases (5.21%) were diagnosed with cervical cancer. From 2013 to 2020, there was a statistically significant decline in the overall incidence of HPV-positive cervical cancer (Z=-4.061, P < 0.001), as well as in the incidence of squamous cell carcinoma (Z=-4.595, P < 0.001). However, the incidence of adenocarcinoma did not exhibit a significant change (Z = 0.118, P = 0.906). Regarding age distribution, a significant decrease in cervical cancer incidence was observed in patients aged 36 to 64 years (Z=-2.658, P = 0.008). In contrast, the incidence remained relatively stable in patients aged 65 years and older (Z = 0.071, P = 0.943). The incidence of squamous cell carcinoma increased with age, peaking at 27.06% in individuals over 65 years. The decline in HPV-positive cervical cancer cases highlights the success of China's screening and post-2016 vaccination efforts. However, rising HPV infections in younger women and ongoing cancer risks in older groups emphasized the need to broaden adolescent vaccinations, sexual health education, and lifelong screening.

HPV genotyping agreement between paired cervical cytological sample and biopsy across lesion severity and vaccination

Cytological samples are genotyped to inform clinical management of HPV-infected women due to their accessibility. Conversely, HPV genotypes identified in biopsies are deemed directly associated with cervical lesions. Thus, investigating genotyping agreement between these two sample types and potential influence of lesion severity and vaccination status on their degree of concordance is essential for understanding their diagnostic reliability. Paired cervical cytological samples and formalin-fixed paraffin-embedded (FFPE) biopsies from 392 cervical intraepithelial neoplasia or cancer (CIN+) cases (187 CIN1, 111 CIN2, 94 CIN3+; 262 unvaccinated, 130 vaccinated) were genotyped using SPF Overall, most HPV genotypes were more frequently detected in cytological samples, with seven genotypes showing statistical differences between sample types (HPV39, 51, 52, 53, 56, 58, 68/73). Multi-type infection was more prevalent in cytological samples (147 versus 76, P In conclusion, HPV genotyping by cytological samples and FFPE biopsies performed equally well regardless of lesion severity and vaccination status, directly supporting reliable utility of cytological HPV genotyping for clinical decisions. However, impact of sample type needs to be considered when interpretating and utilizing multi-type and/or single-type infection for scientific research. ClinicalTrials.gov (NCT00779766). Registered on the 23th of October 2008.

Curcumin nanoemulsion suppresses HPV oncogenes and inhibits cervical cancer progression: in vitro and in vivo study

Cervical cancer represents a major global health problem, ranking as the fourth most prevalent cancer among women across the globe. The primary risk factor associated with cervical intraepithelial neoplasia and cervical cancer is the human papillomavirus (HPV). Curcumin (Cur), extracted from the root of the Curcuma longa plant, is an anticancer, chemoprotective, and gene/protein regulating agent, which refers to its ability to exert beneficial effects in various aspects of cancer prevention and treatment. This study investigated the tumor inhibitory effect (anti-tumoral effect) of a novel curcumin nanoemulsion (Cur-NE) on HPV The MTT assay was used to evaluate the cytotoxicity of Cur-NE and Cur on TC-1 cancer cells and MC3T3 normal cells. In vitro assessment was performed using flow cytometry (Annexin/PI) to examine apoptosis and quantitative PCR (qPCR) analysis to determine the gene expression levels of E6 and E7 human papillomavirus oncogenes, as well as their associated protein factors, p53 and Rb. In addition, C57BL/6 female mice burdening HPV + TC-1 tumor as cervical cancer models were used to investigate the tumor inhibitory effect of the Cur-NE in vivo compared to free curcumin. In vitro anti-tumoral studies showed that apoptosis and inhibiting cellular proliferation in TC-1 cells were induced effectively by curcumin nanoemulsion. Accordingly, curcumin nanoemulsion reduced mRNA expression levels of E6 and E7 HPV oncogenes and increased p53 and Rb levels in a concentration lower than free curcumin (P < 0.05). Furthermore, the suppression and inhibition of subcutaneous TC-1 tumor growth were more pronounced with the curcumin nanoemulsion compared to free curcumin (P < 0.01). These preeminent preclinical results indicate the potential of this curcumin nanoformulation as an efficient treatment approach for cervical cancer.

The potential use of therapeutics and prophylactic mRNA vaccines in human papillomavirus (HPV)

AbstractCervical cancer (CC) and other malignant malignancies are acknowledged to be primarily caused by persistent human papillomavirus (HPV) infection. Historically, vaccinations against viruses that produce neutralizing antibodies unique to the virus have been an affordable way to manage viral diseases. CC risk is decreased, but not eliminated, by HPV vaccinations. Since vaccinations have been made available globally, almost 90% of HPV infections have been successfully avoided. On the lesions and diseases that are already present, however, no discernible treatment benefit has been shown. As a result, therapeutic vaccines that elicit immune responses mediated by cells are necessary for the treatment of established infections and cancers. mRNA vaccines possess remarkable potential in combating viral diseases and malignancy as a result of their superior industrial production, safety, and efficacy. Furthermore, considering the expeditiousness of production, the mRNA vaccine exhibits promise as a therapeutic approach targeting HPV. Given that the HPV-encoded early proteins, including oncoproteins E6 and E7, are consistently present in HPV-related cancers and pre-cancerous lesions and have crucial functions in the progression and persistence of HPV-related diseases, they serve as ideal targets for therapeutic HPV vaccines. The action mechanism of HPV and HPV-related cancer mRNA vaccines, their recent advancements in clinical trials, and the potential for their therapeutic applications are highlighted in this study, which also offers a quick summary of the present state of mRNA vaccines. Lastly, we highlight a few difficulties with mRNA HPV vaccination clinical practice and provide our thoughts on further advancements in this quickly changing sector. It is expected that mRNA vaccines will soon be produced quickly for clinical HPV prevention and treatment. Graphical Abstract

HPV-driven cancers: a looming threat and the potential of CRISPR/Cas9 for targeted therapy

Cervical and other anogenital malignancies are largely caused by E6 and E7 oncogenes of high-risk human papillomaviruses (HPVs), which inhibit important tumor suppressors like p53 and pRb when they are persistently activated. The main goal of traditional treatments is to physically or chemically kill cancer cells, but they frequently only offer temporary relief, have serious side effects, and have a high risk of recurrence. Exploring the efficacy and accuracy of CRISPR-Cas9 gene editing in both inducing death in HPV-infected cancer cells and restoring the activity of tumor suppressors is our main goal. In this study, we propose a novel precision oncology strategy that targets and inhibits the detrimental effects of the E6 and E7 oncogenes using the CRISPR-Cas9 gene editing system. In order to do this, we create unique guide RNAs that target the integrated HPV DNA and reactivate p53 and pRb. Reactivation is meant to halt aberrant cell development and restart the cell's natural dying pathways. This review discusses the potential of CRISPR/Cas9 in targeting HPV oncogenes, with a focus on studies that have demonstrated its promise in cancer treatment. Given the absence of a definitive treatment for papillomavirus infection and its subsequent association with various cancers, future clinical trials and experimental investigations appear essential to establish and evaluate the therapeutic potential of CRISPR-based approaches. This approach provides a less invasive alternative to conventional treatments and opens the door to personalized care that considers the genetic makeup of each patient's tumor.

HPV16 E7 inhibits HBD2 expression by down-regulation of ASK1-p38 MAPK pathway in cervical cancer

Recent researches indicated a down-regulation of Human beta-defensin2 (HBD2) expression in cervical cancer cells, but the mechanism and clinical significance is not clear yet. In this paper, based on the data from the TCGA database, the bioinformatics analysis provided by the UALCAN server was used. The HBD2 mRNA levels were tested with RT-qPCR in cells and protein concentration in cell cultural supernatant was assayed with ELISA. When the gene of Human papillomavirus type 16 E7 oncoprotein (HPV16 E7) overexpression or knockdown, the protein expression of ASK1 and p38 MAPK was detected by Western blot. The bioinformatics analysis results implied that mRNA levels of HBD2 in cervical cancer were lower obviously than healthy people. HBD2 mRNA levels and protein in CaSki and SiHa cells increased obviously under the condition of HPV16 E7 gene silence. However, HBD2 mRNA and protein levels decreased significantly in C33A and CaCo2 cells not only under the conditions of treatment with HPV16 E7 gene overexpression, but also the inhibition of ASK1-p38 MAPK pathway by SB-203580 or GS-4997, or shRNA expression plasmid of ASK1 transefction. Moreover, p-ASK1(Thr845), the activity forming protein of ASK1, and p-p38, decreased in C33A and CaCo2 cells accompanied with HPV16 E7 overexpression, while p-ASK1(Ser966) protein, an inhibitory forming protein kept in a same stable levels. The completely opposite patterns of the protein expression in ASK1-p38 MAPK pathway were obtained in CaSki and SiHa cells transfected with HPV16 E7 siRNA sequence. Interestingly, statistical higher levels of phosphorylated p38 and cellular apoptosis rates, were found in SiHa cells exposed in Anisomycin than in DMSO solution. And increased HBD2 protein concentration in cell cultural supernatant and decreased cell survial rates, were confirmed in CaSki and SiHa cells treatment with Anisomycin, at the same time. Our results implied that HPV16 E7 suppresses HBD2 expression via the inhibition of the ASK1-p38 MAPK signaling pathway, and this mechanism might be a key way of anti-tumor effect of Anisomycin. This study provided a novel insight into the expression and regulation mechanism of HBD2 in tumors and offered a possible therapeutic strategy by using defensins for cervical cancer in future.

Study on the detection rate, genetic polymorphism, viral load, persistent infection capacity, and pathogenicity of human papillomavirus type 33

There is a lack of research on the relations among genetic polymorphisms, viral load, adaptability, persistent infection ability, and pathogenicity of human papillomavirus (HPV) type 33. Understanding these relations is crucial for revealing its pathogenic mechanisms and formulating prevention strategies. Exfoliated cervical cells were harvested from female participants in three hospitals located in the southwestern region of China (Guizhou, Sichuan, and Chongqing). Real-time fluorescence PCR technology was used for HPV genotyping and genomic quantification, and Sanger sequencing was used to obtain the gene sequence. then, changing trends in HPV33 detection rates and E6/E7 allele frequencies were compared. Positive selection, viral load, pathogenicity, and persistent infection capacity of different E6/E7 variants/mutations were analyzed. Among 239,743 samples, HPV detection number was 56,681, the HPV33 detection rate was 3.72% (2,110/56,681) among all detected HPV genotypes. Between 2009 and 2023, a downward trend in the HPV33 detection rate was observed. The E6 + E7 prototype (E6 + E7 on the same variant is consistent with the reference sequence) was the dominant variant, with a significantly increased allele frequency. This dominant variant showed a significantly higher relative risk in causing persistent infection and cervical diseases (cervical intraepithelial neoplasia and cervical cancer). The viral load in the cervical disease group was significantly higher than that in the lesion-free group, and the viral load in the persistent infection group was significantly higher than that in the viral clearance group. There was no correlation between viral load and major genetic variants/mutations. The E6 + E7 prototype has a significant impact on the pathogenicity and persistent infection capacity of HPV33. Viral load is positively correlated with pathogenicity and persistent infection capacity. It may serve as a biomarker for predicting disease progression during HPV33 screening. Other mechanisms underlying allele replacement require further investigation.

Characterization of human papillomavirus genotypes infections in patients with cervical lesions and cervical cancer in Urumqi, Xinjiang from 2016 to 2023

The persistence of high-risk human papillomavirus (HPV) infection is well-established as a key etiological factor in the progression to cervical intraepithelial neoplasia (CIN) and cervical cancer (CC). This study aims to investigate the clinical and epidemiological characteristics associated with HR-HPV infections diagnosed in conjunction with cervical intraepithelial lesions in Urumqi, Xinjiang. Between 2016 and 2023, we collected clinical data from 4,389 patients with cervical lesions who underwent colposcopic histopathological examination at the People's Hospital of Xinjiang Uygur Autonomous Region. Cervical samples were obtained for HPV DNA genotyping and cytological analysis. Patients presenting with cervical abnormalities or abnormal cytology results subsequently underwent cervical biopsy. The prevalence of HPV infection among 4,389 patients with cervical lesions were found to be 98.95% (4,345/4,389). Specifically, the prevalence of HPV types 16 and 18 were 78.87% (1,314/1,666). The five most common genotypes identified were HPV types 16, 52, 58, 31, and 33, with infection rates of 34.57%, 19.54%, 12.45%, 8.98%, and 7.66%, respectively. Among the patients with cervical lesions, cervical inflammation was observed in 522 individuals (11.90%), while the distribution of cervical intraepithelial neoplasia (CIN) was as follows: CIN I in 644 patients (14.67%), CIN II in 1,067 patients (24.31%), CIN III in 1,041 patients (23.72%), and CC in 1,115 patients (25.40%). The distribution of patients in the CC group was most prevalent among those aged ≥ 60 years (47.99%, 322/671). A high prevalence was also observed in the 30~39 year age group within the CIN III group (29.47%, 275/933). Han and Uygur patients accounted for 85.90% of cervical lesion cases (3,770/4,389). Hui patients were predominantly identified within the CIN II group (34.12%), whereas Uighur patients were most frequently observed in CC group (36.60%) (P < 0.005). Patients with cervical lesions had high HPV prevalence in Urumqi, Xinjiang. The five most prevalent HPV types identified in this population are HPV 16, 52, 58, 31, and 33. Epidemiological studies focusing on high-risk HPV types hold significant clinical implications, particularly in informing and guiding HPV vaccination strategies.

Study on the clinical characteristics, persistent infection capability, and viral load of human papillomavirus type 82 single infection

Human papillomavirus (HPV) infection is a key factor in the development of cervical cancer and HPV genotyping is crucial for screening. There are significant differences in the pathogenic potential of the various HPV types. Currently, clinical data on HPV82 are scarce, and the relationship between its viral load, pathogenicity, and persistence is unknown. This study analyzed the characteristics of HPV82 single infection. Cervical samples were collected to determine the positivity rate of HPV82 and its clinical features in a single infection and examined the association between viral load, persistent infection, and pathogenicity. The positive rate of HPV82 among women attending hospitals for gynecological physical examination or medical consultation was approximately 0.24% (1,033/435,072). Among 335 cases of HPV82 single infection, the number of patients with lesion-free tissue biopsy results, cervical intraepithelial neoplasia (CIN) 1, CIN2, CIN3, and cervical cancer were 263, 42, 11, 18, and one, respectively. A follow-up of 210 patients showed that 21.21% (7/33) of patients with CIN1 progressed to high-grade lesions, whereas 7.34% (13/177) of lesion-free patients progressed to CIN. The viral load in the CIN and cervical cancer group was significantly higher than that in the lesion-free group (p < 0.001), and the viral load in the persistent infection group was higher than that in the viral clearance group (p < 0.001). The pathogenicity of single HPV82 infection ranks in the middle among high-risk HPV types, and it can lead to cervical cancer, warranting the inclusion of HPV82 in expanded screening for HPV. High viral load is a significant factor that improves the persistent infection ability and pathogenicity of HPV82. Viral load is expected to serve as a screening risk factor for persistent infection and disease progression associated with HPV82.

Investigation and analysis of female HPV infection and genotype distribution in Xuhui District, Shanghai

In China, Cervical cancer is one of the common malignant tumors in females, and high-risk human papillomavirus (HR-HPV) infection is one of its main causative factors. However, human papillomavirus (HPV) infection rates may vary significantly among patients of different ages and HPV subtypes. This study aims to provide insights into developing cervical cancer screening strategies and selecting HPV vaccine antigen targets in the area. A retrospective analysis was conducted on the HPV testing results of 47,423 women from January 2017 to April 2023 at the Clinical Laboratory of the Eighth People's Hospital in Shanghai. HPV DNA genotyping was performed using real-time quantitative polymerase chain reaction (PCR) in the molecular laboratory. Statistical analysis was carried out using GraphPad Prism 8.0.1 software. Binomial distribution analysis was used to calculate the 95% confidence intervals (95% CI), and the chi-square test was employed to compare categorical variables among different age groups, with a p-value of less than 0.05 indicating statistical significance. Among the 47,423 cervical HPV DNA test results, the overall infection rate was 18.9%, with single infections accounting for 13.93%, dual infections for 3.47%, and multiple infections for 1.5%. The age-specific prevalence of HPV infection exhibited a "U"-shaped curve, with the highest infection rates observed in the age groups under 30 and between 50 and 59 years. The five most common HR-HPV subtypes in Xuhui District were types 16, 39, 51, 52, 56, and 58 (accounting for 10.3%, 7%, 8%, 20.3%, 6%, and 12%, respectively), with type 52 showing the highest infection rate. The prevalence of moderate/severe HPV infection rates in the HPV 59, HPV 33, and HPV 35 gene subtypes increased over time, highlighting the importance of monitoring these subtypes. This study identified the primary HR-HPV genotypes prevalent among females in Xuhui District, Shanghai, and explored correlations between age, genotype, and HPV infection rates. While the findings provide a basis for recommending HPV screening for younger and older age groups, further studies integrating clinical outcomes such as cytological and pathological results are necessary to substantiate these conclusions and refine screening strategies. Due to variations in HPV trends globally and regional differences in genotypes, epidemiological analysis of HPV can accurately and visually reflect the distribution of specific HPV genotypes in a particular area, thereby aiding in the development of regional cervical cancer screening strategies and the selection of HPV vaccine antigen targets.

Genotypic analysis of human papillomavirus in cervical exfoliated cells from women in Zigong

This study investigated the human papillomavirus (HPV) infection status among women in Zigong from January 2016 to August 2024 and provides a comprehensive statistical analysis of HPV infection characteristics. The findings aim to enhance cervical cancer screening, inform vaccination strategies, and improve HPV infection prevention measures. We conducted a retrospective analysis on 48,474 female patients who visited the gynecology department of Zigong Fourth People's Hospital from January 2016 to August 2024. Cervical exfoliated cell samples were collected from the patients, and the genotypes of 10 low-risk HPV (LR-HPV) and 17 high-risk HPV (HR-HPV) were detected by flow fluorescent hybridization technique. The study explored HPV infection rates, genotype distribution, number of infections, type of infections, and age distribution. The chi-squared (χ Among the 48,474 patients, 9749 tested positive for HPV, with an overall infection rate of 20.11%. The HPV infection rate increased gradually from 2016 to 2024 (P < 0.001). The infection rates of single, double, triple, and ≥ quadruple infections were 15.11%, 3.54%, 1.00%, and 0.46%, respectively. The infection rates were 4.41% for LR-HPV-only, 13.13% for HR-HPV-only, and 2.57% for mixed LR and HR-HPV. HR-HPV primarily consisted of HPV types 52, 16, 53, and 58, with infection rates of 3.94%, 2.71%, 2.43%, and 2.42%, respectively. LR-HPV primarily consisted of types 61 and 81, with infection rates of 1.64% and 1.49%, respectively. A significant age correlation in HPV infection was observed (P < 0.001), with two distinct peaks in infection rates. The HPV infection rate among women visiting the gynecology department in Zigong is high, predominantly involving HPV types 52, 16, 53, and 58. Therefore, strengthening HPV screening efforts and focusing on standardized genotype screening is crucial. Additionally, selecting HPV vaccines targeting prevalent genotypes and actively conducting HPV prevention and control work can reduce the incidence of HPV-related cervical cancer and other HPV-related diseases.

Study on the clinical characteristics, persistent infection capability and viral load of human papillomavirus type 26 single infection

Human papillomavirus (HPV) infection is the main cause of cervical cancer. Different types of HPV have varying carcinogenic capabilities, and viral load is one of the key indicators of pathogenicity. Currently, there is a lack of clinical data on HPV26. This study analyzed the clinical characteristics of patients with HPV26 single infection. Exfoliated cervical cells were collected for HPV genotyping from women who attended gynecological outpatient clinics or physical examinations. The clinical characteristics of HPV26 single infections in both cross-sectional and follow-up studies were examined, and the association of viral load with HPV26 persistent infection and pathogenicity was investigated. The HPV26 positive rate among women visiting hospitals for gynecological medical consultation or physical examination was approximately 0.09% (379/435,072). Among the HPV types tested, the detection rate of HPV26 was 0.37% (379/103,608). In the cross-sectional histopathological study of 101 patients with HPV26 single infection, 62.37% (63/101) presented lesion-free. The numbers of patients with cervical intraepithelial neoplasia (CIN) 1, CIN2, and CIN3 were 25, eight, and five, respectively. Cervical cancer was not detected in any patient. 71 patients attended follow-up examinations as well as HPV26 retesting up to two years, during which, 28.57% (6/21) of CIN1 patients have developed into high-grade lesions, and 9.61% (5/52) of lesion-free patients have progressed to CIN stage. The viral load in the CIN group was significantly higher than that in the lesion-free group (p = 0.012). Similarly, the viral load in the persistent infection group was significantly higher than that in the viral-clearance group (p < 0.001). The pathogenicity of single HPV26 infections is moderate among high-risk types, warranting the inclusion of HPV26 in expanded screening for HPV. High viral load is an important factor in the persistent infection and pathogenicity of HPV26. Viral load is expected to serve as a screening risk factor for persistent infection and disease progression associated with HPV26.

Influence of COVID-19 pandemic on prevalence and genotype distribution of HPV in cervical cancer screening population

Human Papillomavirus (HPV) DNA screening was a crucial element in the fight against cervical cancer and had been adopted in many countries, including China. However, the onset of the COVID-19 pandemic in March 2020 disrupted this program significantly. The aim of this study is to investigate the prevalence and distribution of HPV genotypes among the population undergoing cervical cancer screening during the pandemic period. From January 2017 to December 2022, Peking Union Medical College Hospital gathered 45,496 cervical swabs from individuals undergoing cervical cancer screening. These samples were analyzed to detect fifteen high-risk HPV (HR-HPV) DNA types and a combination of two low-risk HPV (LR-HPV) types. The study revealed an overall infection rate of 11.24% (5,114/45,496), with 11.06% (5,032/45,496) of individuals infected with HR-HPV. The number of HPV screening patients and the infection rates of HPV, HR-HPV, LR-HPV, multiple genotype HPV (M-HPV), and single genotype HPV (S-HPV) during the pandemic were lower than those observed before the pandemic. Moreover, the age group with the highest percentage of infected individuals was under 45-49 years, with HPV52, HPV58, HPV16, and HPV51 being the most prevalent genotypes. Notably, HPV66 emerged as the fifth most commonly detected genotype during the pandemic. Additionally, among the eleven age groups examined, women under 25 exhibited the highest detection rate, with HPV52 and HPV16 infection rates exceeding those observed in the pre-pandemic period. The findings of this study offer significant insights for shaping HPV prevention strategies and enhancing cervical cancer screening initiatives in China following the epidemic.

Oncolytic activity of a coxsackievirus B3 strain in patient-derived cervical squamous cell carcinoma organoids and synergistic effect with paclitaxel

Cervical squamous cell carcinoma (CSCC) is a prevalent gynecological malignancy worldwide. Current treatments for CSCC can impact fertility and cause long-term complications, underscoring the need for new therapeutic strategies. Oncolytic virotherapy has emerged as a promising option for cancer treatment. Previous research has demonstrated the oncolytic activity of the coxsackievirus B3 strain 2035 A (CVB3/2035A) against various tumor types. This study aims to evaluate the clinical viability of CVB3/2035A for CSCC treatment, focusing on its oncolytic effect in patient-derived CSCC organoids. The oncolytic effects of CVB3/2035A were investigated using human CSCC cell lines in vitro and mouse xenograft models in vivo. Preliminary tests for tumor-selectivity were conducted on patient-derived CSCC tissue samples and compared to normal cervical tissues ex vivo. Three patient-derived CSCC organoid lines were developed and treated with CVB3/2035A alone and in combination with paclitaxel. Both cytotoxicity and virus replication were evaluated in vitro. CVB3/2035A exhibited significant cytotoxic effects in human CSCC cell lines and xenograft mouse models. The virus selectively induced oncolysis in patient-derived CSCC tissue samples while sparing normal cervical tissues ex vivo. In patient-derived CSCC organoids, which retained the immunohistological characteristics of the original tumors, CVB3/2035A also demonstrated significant cytotoxic effects and efficient replication, as evidenced by increased viral titers and presence of viral nucleic acids and proteins. Notably, the combination of CVB3/2035A and paclitaxel resulted in enhanced cytotoxicity and viral replication. CVB3/2035A showed oncolytic activity in CSCC cell lines, xenografts, and patient-derived tissue cultures and organoids. Furthermore, the virus exhibited synergistic anti-tumor effects with paclitaxel against CSCC. These results suggest CVB3/2035A could serve as an alternative or adjunct to current CSCC chemotherapy regimens.

Lineage and sublineage analysis of human papillomavirus type 58 in iranian women

Variant analysis of distinct HPV types is important from different aspects including epidemiology, pathogenicity, and evolution. For this reason, the full sequence of the E6 and E7 genes of HPV 58 was examined in 130 HPV 58-infected cervical samples using PCR and sequencing. Our results revealed that three lineages A, B, and D were found in this study; among which the B lineage was more common (91.50%). About sublineages, all samples of the B lineage belonged to the B1 sublineage, and samples that were classified as the A and D lineages were found to belong to the A1 (0.77%), A2 (5.38%), A3 (1.50%), and D2 (0.77%) sublineages. No statistically significant differences were found between lineages and stages of disease or amino acid changes (P > 0.05). Our results showed that lineage B, sublineage B1, was dominant in Iran. However, more studies with larger sample sizes from different parts of Iran are essential for assessing the pathogenicity risk of HPV 58 lineages in Iranian women with cervical cancer.

The cervical cancer related distribution, coinfection and risk of 15 HPV types in Baoan, Shenzhen, in 2017–2023

AbstractCervical cancer is one of the most common malignant tumours. Human papillomavirus (HPV) infection is the main cause of this cancer so that it could be prevented by screening and early treatment. Developing reginal screen protocols of maximum public health efficacy requires in-depth understandings of local HPV distribution and consequential cancer risks. Therefore, test results of HPV genotyping, cytology testing (TCT) and colposcopy inspection with biopsy were collected in this retrospective research. Data included by this research involved 63,906 women received screen related tests from Shenzhen Baoan Shiyan People’s Hospital and the subsidiary institutes between 2017.01 and 2023.05. 10,238 colposcopies were performed in this period collecting 8,716 samples and 814 high-grade CIN were discovered. Within the 763 high-grade CIN cases with both TCT and HPV testing results, 232 were tested cytologically normal but only 30 were negative in HPV test. Besides, the rates of high-grade CIN observed in coinfection were all lower than the estimated rates generated from related single infection. HPV 52, 58 and 16 were found to be the most common types in Baoan, Shenzhen. The result also suggested that HPV coinfections should not increase risk for cervical cancers.

The prevalence and genotype distribution of high-risk human papillomaviruses among women in Xianning, China

Abstract Background The persistent infection of high-risk Human papillomavirus(HPV) is considered the main cause of cervical intraepithelial neoplasia and cervical cancer. But various cervical lesions caused by HPV infection can be properly prevented by timely vaccination. However, the distribution of HPV genotypes varies geographically. Methods Retrospective analysis of high-risk HPV prevalence of 16,150 women from 2020 to 2022 in xianning of China. HPV genotyping was performed using a PCR-RDB Kit that can detect 18 high-risk HPV genotypes recommended by China’s National Medical Products Administration. The prevalence of 18 high-risk HPV genotypes and their relationship with cervical lesions as well as vaccine efficacy were analyzed. Results A total of 2431 women were confirmed to have different types of high-risk HPV infections. The overall positive rate reached 15.05%(2431/16,150). The most prevalent high-risk HPV genotypes were HPV52, 16, 58, 53, and 51. The prevalence of high-risk HPV reached peak at age ≤ 20(20.95%) and age ≥ 61(20.56%). The most prevalent high-risk HPV genotypes were HPV16, 58, 18, 33 and 52 in cervical cancer cases, HPV16, 52, 58, 33 and 18 in CIN2/3 cases, and HPV52, 58, 16, 53 and 18 in CIN1 cases, respectively. Conclusion HPV16, 58 and 18 are the most dangerous and carcinogenic genotypes in xianning, China. Conducting epidemiological investigations on high-risk HPV has significant clinical value in guiding HPV vaccination work.

Management for persistent HPV infection and cervical lesions among women infected with HIV: a retrospective observational cohort study

Abstract Background Early diagnosis and treatment of HPV persistent infection and cervical intraepithelial neoplasia, which have yet to be thoroughly characterized in Guangxi, Southwestern China, are the key preventative measures for the development of cervical cancer in women, particularly in HIV-infected women. Methods A retrospective study of 181 patients with HPV infection or cervical intraepithelial neoplasia who received surgical excision of lesions and were prospectively enrolled at the Fourth People’s Hospital of Nanning between January 2018 and February 2023 was performed. HPV-infected patients were divided into two subgroups: HIV-infected and HIV/HPV-coinfected patients and compare differences between these groups. Results HPV16, 18, 52, and 58 were the most prevalent HPV genotypes. High-risk HPV was significantly co-infected with multiple genotypes (P = 0.0332). HIV-infected women were predisposed to HPV infection (P &lt; 0.0001), and the development of cervical cancer at a young age (P = 0.0336) compared to HIV-uninfected women and the loop electrosurgical excision procedure (P = 0.0480) is preferred for the treatment. Conclusions HIV infection may increase HPV prevalence and lead to cervical cancer development at a young age. The loop electrosurgical excision procedure is an efficient evaluation and treatment strategy for HIV-infected women suffering from cervical intraepithelial neoplasia.

Nonlinear relationship between viral load and TCT in single/multiple HPV52 infection

Abstract Purpose To determine the correlation between HPV (human papillomavirus) 52 viral load, multiple infections and ThinPrep cytology test (TCT), to inform clinical management of HPV52-positive women after cervical cancer screening. Methods A total of 1,882 female patients who had positive quantitative HPV tests at Yuebei People's Hospital from January 2020 to December 2022, of whom 533 tested positive for HPV52. We excluded patients who combined HPV16 and/or HPV 18 positivity and whom HPV52 viral load could not be calculated. The final enrollment was 488 patients, including 400 NILM, 48 ASC-US, 28 LSIL and 12 HSIL. The HPV test is a quantitative multiplexed fluorescent PCR assay that provides both HPV genotyping and viral load. Results In our study, there were differences in the median distribution of viral loads among various cytological class categories. The risk of TCT results (LSIL or worse) was increased with the increase of HPV52 viral load, for every LOG unit increase in HPV52 viral load, the risk increased by 26.6%. More importantly, we found a nonlinear relationship between HPV52 viral load and TCT results (LSIL or worse) in both single and multiple infections. When the viral load reaches a threshold, the risk of abnormal cytological results increases significantly. Conclusion HPV52 viral load is an independent risk factor for TCT results (LSIL or worse). The relationship between HPV52 viral load and TCT results (LSIL or worse) is not linear. Viral load may be used as a triage indicator for HPV52-positive patients, thus improving the post-screening clinical management of HPV52-positive women.

Association between human herpesvirus infection and cervical carcinoma: a systematic review and meta-analysis

Abstract Background Cervical cancer (CC) is one of the most common gynecologic tumors among women around the world. Although the etiological role of human papillomavirus (HPV) in CC is well established, other factors in CC carcinogenesis remains unclear. Here, we performed a systematic review and meta-analysis to explore the association between infections of human herpesvirus (HHVs) and CC risk. Methods Embase and PubMed databases were utilized to search the relevant studies. The revised JBI Critical Appraisal Tool was used to assess the quality of the included studies. Prevalence and odds ratios (ORs) with 95% confidence intervals (CI) were calculated to evaluate the association between viral infection and CC or precancerous cervical lesions (PCL). Results Totally 67 eligible studies involving 7 different HHVs were included in meta-analysis. We found an increased risk of CC or PCL that was associated with the overall infection of HHVs (CC, OR = 2.74, 95% CI 2.13–3.53; PCL, OR = 1.95, 95% CI 1.58–2.41). Subgroup analysis showed a trend towards positive correlations between herpes simplex virus type 2 (HSV-2) infection and CC (OR = 3.01, 95% CI 2.24 to 4.04) or PCL (OR = 2.14, 95% CI 1.55 to 2.96), and the same is true between Epstein-Barr virus (EBV) infection and CC (OR = 4.89, 95% CI 2.18 to 10.96) or PCL (OR = 3.55, 95% CI 2.52 to 5.00). However, for HSV-1 and cytomegalovirus (HCMV), there was no association between viral infection and CC or PCL. By contrast, the roles of HHV-6, HHV-7, and Kaposi sarcoma–associated herpesvirus (KSHV) in cervical lesions were unclear due to the limited number of studies. Conclusions This study provided evidence that HHVs infection as a whole increase the risk of CC incidence. In addition, some types of HHVs such as EBV and HSV-2 may serve as potential targets in the development of new interventions or therapeutic strategies for cervical lesions.

Prevalence and genotype distribution of human papillomavirus infection among women in Jingzhou, China: a population-based study of 51,720 women

Abstract Background Cervical cancer is the fourth most common cancer among women worldwide with a serious threat to women’s health. Persistent infection with high-risk human papillomavirus (HR-HPV) has been identified as the main cause of cervical cancer. This study aimed to evaluate the prevalence and genotype distribution of HR-HPV among women in Jingzhou, Hubei province, China, which is critical for the government to formulate the precision strategies of cervical cancer screening and HPV vaccine innoculation. Methods To obtain the baseline data on the population-based prevalence and genotype distribution of HR-HPV infection among age groups and different years, a total of 51,720 women from 2018 to 2022 who went to Jingzhou Hospital Affiliated to Yangtze University for physical examination or gynacological treatment and received HR-HPV DNA genotyping were included in this retrospective study. The possible cervicovaginal infection of 15 high-risk HPV genotypes were analyzed by multiplex fluorescent real-time PCR, including HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68 and 82. Results The overall high-risk HPV prevalence among 51,720 women was 18.75% (9,698/51,720), and the HPV-positive rate of physical examination group (PEG) was 13.22% (541/4,091), which was lower than the HPV-positive rate of gynacological checkup group (GCG) 19.23% (9,157/47,629), with statistical difference (χ2 = 89.069, P &lt; 0.01). The five most common prevalent genotypes were HPV52 (6.55%), HPV58 (3.41%), HPV16 (2.58%), HPV68 (1.82%) and HPV51 (1.57%). Single HPV infection was the predominant (14.36%), which compared to double (3.34%) and multiple (1.05%) infections. The HPV-positive rate was the highest in the &gt; 60 age group (31.73%), and the lowest in the 31–40 age group (15.46%). Conclusions The prevalence of high-risk HPV infection among women in Jingzhou area was 18.75%. HPV52, HPV58 and HPV16 genotypes were the most common. The higher prevalence was in the &gt; 60 and ≤ 20 age group, which showed a “U” shape curve, suggesting the necessity of screening among older women to decrease the mortality of cervical cancer.

Bioinformatics analysis of immune characteristics in tumors with alternative carcinogenesis pathways induced by human papillomaviruses

Abstract Background Human papillomaviruses (HPVs) induce a subset of head and neck squamous cell carcinomas (HNSCC) and anogenital cancers, particularly cervical cancer (CC). The major viral proteins that contribute to tumorigenesis are the E6 and E7 oncoproteins, whose expression is usually enhanced after the integration of viral DNA into the host genome. Recently, an alternative tumorigenesis pathway has been suggested in approximately half of HNSCC and CC cases associated with HPV infection. This pathway is characterized by extrachromosomal HPV persistence and increased expression of the viral E2, E4, and E5 genes. The E6, E7, E5, and E2 proteins have been shown to modify the expression of numerous cellular immune-related genes. The antitumor immune response is a critical factor in the prognosis of HPV-driven cancers, and its characterization may contribute to the prediction and personalization of the increasingly used cancer immunotherapy. Methods We analyzed the immune characteristics of HPV-dependent tumors and their association with carcinogenesis types. Transcriptomic HNSCC and CC datasets from The Cancer Genome Atlas were used for this analysis. Results Clustering with immune-related genes resulted in two clusters of HPV16-positive squamous cell carcinomas in both tumor types: cluster 1 had higher activation of immune responses, including stimulation of the antigen processing and presentation pathway, which was associated with higher immune cell infiltration and better overall survival, and cluster 2 was characterized by keratinization. In CC, the distribution of tumor samples into clusters 1 and 2 did not depend on the level of E2/E5 expression, but in HNSCC, most E2/E5-high tumors were localized in cluster 1 and E2/E5-low tumors in cluster 2. Further analysis did not reveal any association between the E2/E5 levels and the expression of immune-related genes. Conclusions Our results suggest that while the detection of immune responses associated with preserved expression of genes encoding components of antigen processing and presentation machinery in HPV-driven tumors may be markers of better prognosis and an important factor in therapy selection, the type of carcinogenesis does not seem to play a decisive role in the induction of antitumor immunity.

Epidemiology and genotypes analysis of human papillomavirus infection in Beijing, China

Abstract Background This study aimed to investigate the epidemiology of high-risk human papillomavirus (HPV) in the female population in Beijing, China, and identify the relationship between HPV genotypes and host factors. Methods HPV testing was performed on women aged 15–89 (mean age 38.0 ± 10.9 years) from Beijing in 2020. High-risk HPV genotyping real-time polymerase chain reaction was used to determine HPV genotypes. The overall prevalence, age-specific prevalence, genotype distribution, and the correlation between HPV genotypes and cervical cytology were analyzed. Results Among the 25,344 study participants, the single and double infection rates were 18.8% (4,777/25,344) and 4.2% (1,072/25,344), respectively. A total of 6,119 HPV-positive individuals were found to have 91.6% negative results for intraepithelial lesion or malignancy (NILM), 5.8% atypical squamous cells of undetermined significance (ASC-US), 0.9% low-grade squamous intraepithelial lesion (LSIL), and 1.7% high-grade squamous intraepithelial lesion (HSIL). In single HPV infections, the HPV16 genotype was highly associated with cervical cytology severity (χ2 trend = 172.487, P &lt; 0.001). Additionally, HPV infection rates increased gradually with age, and statistical differences were observed across age groups (χ2 = 180.575; P &lt; 0.001). High-risk HPV genotypes were highly prevalent in women below 25 years of age and those aged 55–59 years. Cluster analysis revealed that the 13 HPV genotypes could be roughly divided into two groups in a single infection; however, patterns of infection consistent with biological characteristics were not observed. Conclusion High-risk HPV was found in 24.1% of outpatients, with HPV52, HPV58, HPV16, HPV39, and HPV51 being the most common high-risk genotypes. Single high-risk HPV infection was predominant. HPV16, HPV39, HPV51, and HPV52 were associated with cervical lesion progression. HPV16 infection was especially worrying since it aggravates cervical lesions. Because the infection rates of the 13 HPV genotypes differed by age, the peak HPV infection rate should not guide vaccination, screening, and prevention programs. Instead, these initiatives should be tailored based on the regional HPV distribution characteristics. Moreover, it was determined that Beijing’s populace needed to receive treatment for HPV39 infection.

Characteristics of human papillomavirus prevalence and infection patterns among women aged 25–64 according to age groups and cytology results in Ordos City, China

Abstract Background The assessment of human papillomavirus (HPV) genotype distribution in terms of age and cervical lesions could contribute to the adoption of more targeted preventive approaches to specific populations against cervical cancer. The current study was conducted in Ordos City, China, with the aim of analyzing the HPV genotypes prevalence and infection patterns within a hospital-based population. Methods The analysis included a total of 26,692 women aged 25–64 who underwent cervical cancer screening between January 1st, 2019, and June 30th, 2022, in Ordos City. These women had valid results for both the polymerase chain reaction (PCR)-reverse dot blot (RDB) HPV test and the liquid-based cytology (thinprep cytologic test/TCT). Data were extracted from the database of KingMed Diagnostics laboratories. The prevalence of HPV genotypes within different age groups and cytology diagnoses were calculated. Results Among 26,692 women, 7136 (26.73%) women were HPV positive, 5696 (21.34%) women were high-risk HPV (HR-HPV) positive, and 2102 (7.88%) women had multiple HPV infections. The most frequently detected HPV genotypes were HPV16 (4.72%) and HPV52 (4.15%), ranking as the first and second most prevalent genotypes, respectively. The prevalence of HR-HPV increased with age groups and severity of cervical lesions. Notably, the positive rate of HR-HPV among women aged 35–64 years showed a decreasing trend over the respective years, ranging from 26.00 to 19.70% (Ptrend &lt; 0.001). Conclusion In conclusion, the epidemiology of HPV genotypes partly reflects the effectiveness of regional cervical cancer prevention and control efforts in the past. These findings can inform future initiatives concerning HPV vaccination and screening in the region.

Prevalence and genotype distribution of human papillomavirus infection among 66000 women from 2014 to 2023 in the plateau region of Southwest China

Persistent infection with high-risk human papillomavirus (HR-HPV) plays a key role in the onset of cervical cancer. This study was designed to examine the epidemiological trends and genotype distribution of HPV from 2014 to 2023 in the plateau region of Southwest China. The findings could offer valuable insights for clinical screening of cervical cancer and the formulation of HPV vaccination policies. This retrospective study analyzed 66,000 women who received HPV-DNA testing at the First People's Hospital of Qujing, Yunnan, China, between 2014 and 2023. The cohort consisted of 33,512 outpatients, 3,816 inpatients, and 28,672 individuals undergoing health examinations. Cervical cells were collected for DNA extraction, and PCR amplification along with Luminex xMAP technology were used to detect 27 HPV genotypes. The data analysis was conducted using GraphPad Prism and IBM SPSS Statistics 27 software. The overall HPV infection rate at the First People's Hospital of Qujing declined from 24.92% in 2014 to 16.29% in 2023, averaging 16.02%. Specific infection rates were 18.50% among outpatients, 12.97% among inpatients, and 13.53% for health examination attendees. The predominant high-risk HPV genotypes identified were HPV52 (2.61%), HPV16 (2.06%), HPV58 (1.81%), HPV53 (1.55%), and HPV39 (1.09%). Meanwhile, the most frequent low-risk HPV genotypes were HPV6 (1.30%), HPV61 (1.21%), and HPV11 (0.85%). In HPV-positive cases, the distribution of single, double, triple, and quadruple or more infections were 79.90%, 15.17%, 3.59%, and 1.33%, respectively. The proportions of pure LR-HPV, pure HR-HPV, and mixed infections were 22.16%, 67.82%, and 10.02%, respectively. Age-specific analysis revealed a bimodal distribution of HPV infection, with the infection rate rapidly decreasing from 44.02% in the ≤ 19 age group to 19.55% in the 20-29 age group and 13.84% in the 30-39 age group, followed by a gradual increase to 14.64% in the 40-49 age group, 16.65% in the 50-59 age group, and 22.98% in the ≥ 60 age group. The coverage rates of the three available vaccines are all below 50%. The results of this study indicated a declining trend in HPV prevalence in the plateau region of Southwest China over the period from 2014 to 2023, especially in the reduction of genotypes targeted by vaccines. There were significant variations in the genotypes prevalent among different age groups, years, and patient sources within the same region. The underwhelming vaccination rates emphasize the critical need for developing either a multivalent vaccine or a personalized vaccine that targets the HPV genotypes common in the Chinese population. Furthermore, vaccinating adolescents to curb HPV infection and ensuring regular cervical cancer screenings for postmenopausal women are crucial steps.

Genetic variation of E6 and E7 genes of human papillomavirus type 16 from central China

Abstract Background Persistent high-risk human papillomavirus (HR-HPV) infection is an important factor in the development of cervical cancer, and human papillomavirus type 16 (HPV-16) is the most common HR-HPV type worldwide. The oncogenic potential of HPV-16 is closely related to viral sequence variation. Methods In order to clarify the variant characteristics of HPV-16 E6 and E7 genes in central China, E6 and E7 sequences of 205 HPV‐16 positive samples were amplified by polymerase chain reaction. PCR products of E6 and E7 genes were further sequenced and subjected to variation analysis, phylogenetic analysis, selective pressure analysis and B-cell epitope prediction. Results Twenty-six single nucleotide variants were observed in E6 sequence, including 21 non-synonymous and 5 synonymous variants. Twelve single nucleotide variants were identified in E7 sequence, including 6 non-synonymous and 6 synonymous variants. Four new variants were found. Furthermore, nucleotide variation A647G (N29S) in E7 was significantly related to the higher risk of HSIL and cervical cancer. Phylogenetic analysis showed that the E6 and E7 sequences were all distributed in A lineage. No positively selected site was found in HPV-16 E6 and E7 sequences. Non-conservative substitutions in E6, H31Y, D32N, D32E, I34M, L35V, E36Q, L45P, N65S and K75T, affected multiple B-cell epitopes. However, the variation of E7 gene had little impact on the corresponding B-cell epitopes (score &lt; 0.85). Conclusion HPV-16 E6 and E7 sequences variation data may contribute to HR-HPV prevention and vaccine development in Jingzhou, central China.

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

Abstract Background Human 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. Methods Polymerase 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. Results The overall prevalence rate of HPV infection among 181,705 cases was 23.28%, the prevalence of HR-HPV at the age group &lt; 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 &lt; 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. Conclusions The 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 (&gt; 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.

Cervical carcinogenesis risk association of HPV33 E6 and E7 genetic variations in Taizhou, Southeast China

Abstract Background Human papillomavirus (HPV) 33 belongs to the Alphapapillomavirus 9 (α-9 HPV) species group, which also contains types 16, 31, 35, 52, 58 and 67. The purpose of this study was to investigate the genetic variations of HPV33 and to explore its carcinogenicity among women in Taizhou, Southeast China. Methods Exfoliated cervical cells were collected for HPV genotyping. Only single HPV33 infection cases were selected, and their E6 and E7 genes were sequenced using the ABI 3730xl sequencer and then analysed using MEGA X. Results From 2014 to 2020, a total of 185 single HPV33-positive specimens were successfully amplified. We obtained 15 distinct HPV33 E6/E7 variants, which were published in GenBank under accession numbers OQ672665-OQ672679. Phylogenetic analysis revealed that all HPV33 E6/E7 variants belonged to lineage A, of which 75.7% belonged to lineage A1. Compared with CIN1, the proportion of sublineage A1 in CIN2/3 was higher, but there was no significant difference (76.5% vs. 80.6%, P &gt; 0.05). Altogether, 20 single nucleotide substitutions were identified, of which 6 were novel substitutions, including T196G (C30G), A447T, G458T (R117L), G531A, A704A, and C740T. In addition, no significant trends were observed between the nucleotide substitutions of HPV33 E6/E7 variants and the risk of cervical lesions. Conclusion This study provides the most comprehensive data on genetic variations, phylogenetics and carcinogenicity of HPV33 E6/E7 variants in Southeast China to date. The data confirmed that cervical lesions among women in Taizhou are attributable to HPV33, which may be due to the high infection rate of sublineage A1 in the population.

Transcriptional activity of the long control region in human papillomavirus type 33 intratype variants

Abstract Background High-risk human papillomaviruses (HPVs) are responsible for the development of cervical and other anogenital cancers. Intratype sequence variants of certain high-risk HPV types (e.g. 16, 18 and 31) are thought to have different oncogenic potential, partly due to nucleotide sequence variation in the viral long control region (LCR). The LCR has an important role in the regulation of viral replication and transcription. The purpose of this study was to explore sequence variation in the LCR of HPV 33 intratype variants in Hungary and to see whether there are differences in the transcriptional activities of the variants. Methods The complete HPV 33 LCR was amplified from HPV 33 positive cervical samples. After sequencing the LCR variants, multiple sequence alignment and phylogenetic analyses were carried out. Representative HPV 33 LCR sequence variants were selected for cloning and functional analysis. After transient transfection of HeLa cells, luciferase reporter assays were used to analyse the transcriptional activities of different LCR variants. Results Altogether 10 different variants were identified by sequence analysis of the HPV 33 LCR. The results of phylogenetic analysis showed that 3 variants belonged to sublineage A1, while the other 7 variants clustered with sublineage A2. Variants belonging to sublineage A2 had significantly lower transcriptional activities than variants belonging to sublineage A1. Within sublineage A2, the two variants analysed had significantly different transcriptional activities, which was shown to be caused by the A7879G variation. Conclusions Nucleotide variation in the HPV 33 LCR can result in altered transcriptional activity of the intratype variants. Our results can help to understand the correlation between LCR polymorphism and the oncogenic potential of HPV 33 variants.

The features of high-risk human papillomavirus infection in different female genital sites and impacts on HPV-based cervical cancer screening

Abstract Background The causal role of high-risk Human papillomavirus (HR-HPV) in the pathogenesis of anogenital cancers is well established. In contrast, information on HR-HPV distribution of continuous anatomic sites within the female genital tract is limited, and the impact of sample type on the clinical performance in HPV-based cervical cancer screening warrants investigation. Methods A total of 2,646 Chinese women were enrolled in the study from May 2006 to April 2007. We analyzed the infection features by infection status and pathological diagnoses of 489 women with complete HR-HPV type and viral load data on the cervix, upper vagina, lower vagina, and perineum samples. Additionally, we assessed the clinical performance for detecting high-grade cervical intraepithelial neoplasia of grade two or worse (≥ CIN2) among these four types of samples. Results HR-HPV positivity rate was lower in the cervix (51.53%) and perineum (55.83%), higher in the upper (65.64%) and lower vagina (64.42%), and increased with the severity of cervical histological lesions (all P&lt;0.001). Single infection was more dominant than multiple infections at each anatomic site of the female genital tract. The proportion of single HR-HPV infection decreased successively from the cervix (67.05%) to the perineum (50.00%) (Ptrend=0.019) in cervical intraepithelial neoplasia grade 1 (CIN1) and was higher in samples of the cervix (85.11%) and perineum (72.34%) in ≥ CIN2. In addition, the highest viral load was observed in the cervix compared to the other three sites. The overall agreement of the cervical and perineum samples was 79.35% and increased continuously from normal (76.55%) to ≥ CIN2 (91.49%). As for the detection of ≥ CIN2, the sensitivity was 100.00%, 97.87%, 95.74%, and 91.49% for the cervix, upper vagina, lower vagina, and perineum samples, respectively. Conclusions Single HR-HPV infection predominated throughout the female genital tract, but the viral load was lower compared to multiple HR-HPV infections. Despite the decreasing viral load from cervix to perineum, the clinical performance for detecting ≥ CIN2 of the perineum sample was comparable to that of the cervix.

Prevalence and genotype distribution of HPV and cervical pathological results in Sichuan Province, China: a three years surveys prior to mass HPV vaccination

Abstract Background HPV persistent infection is a strong carcinogenic factor that can induce cervical cancer. Investigation of HPV epidemiology and genotype distribution is of great meaning for the development of cervical cancer prevention and control strategies. Methods By using PCR-based hybridization gene chip assay, HPV genotype was detected from 14,185 women that came from HEC (Health Examination Center) or OGOC (Obstetrics and Gynecology Outpatient Clinics) between 2015 and 2017 in Sichuan area. The epidemiology and genotype distribution as well as the relationship between HPV infection and histology/cytology abnormalities were analyzed. Results The positivity rate of HPV was 23.84%. The HPV-positive rate of OGOC group (37.62%) was significantly higher than that of HEC group (15.29%), p  &lt; 0.05. The prevalence of HPV reached peak at age 41–50 (5.86%) in HEC group, but at age 21–30 (14.74%) in OGOC group. Of all the HPV positive women, single genotype infection was the most common form in both HEC and OGOC group (62.06% in total screening population, 74.36% in HEC group and 54.01% in OGOC group). Three most prevalent HPV types were HPV-52 (5.02%), 58 (3.61%), and 16 (3.24%) in total screening population. Of all the HPV positive women, the top three types were HPV-52 (20.93%), CP8304 (15.32%), and 58 (14.42%) in HEC group, while were HPV-52 (21.14%), 16 (16.34%), and 58 (15.61%) in OGOC group. HPV 52/16/58 accounted for 41.84% of cytology and 56.52% of histological abnormalities. Conclusions Women in Sichuan area were facing the great threat of HPV infection, especially the women aged between 21 ~ 30 or 41–50 years old. The priority HPV types were HPV 52, 58, and 16 in OGOC group, while were HPV 52, CP8304, and 58 in HEC group. HPV 52/16/58 accounted for the majority of cytology and histological abnormalities. Our analysis was found to be valuable for providing a scientific basis for the prevention and control strategies of cervical cancer in Sichuan area.

Lineage analysis of human papillomavirus type 39 in cervical samples of Iranian women

AbstractBackgroundThe data with regards to the regional variants of distinct HPV types is of great value. Accordance with this, this study aimed to investigate the sequence variations of E6 gene and long control region of HPV 39 among normal, premalignant and malignant cervical samples in order to characterize the frequent HPV 39 variants circulating in Tehran, Iran.MethodsIn total, 70 cervical samples (45 normal, 16 premalignant, and 9 malignant samples) infected with HPV 39 were analyzed by nested-PCR and sequencing.ResultsOur results revealed that all samples belonged to A lineage. Almost all sequences (98.6%) were classified in A1 sublineage and only one sample (1.4%) was A2 sub lineage.ConclusionsOur findings showed that lineages A, sublineage A1, is dominant in Tehran, Iran. However, the small sample size was the most important limitations of this study. Further studies with larger sample size from different geographical regions of Iran are necessary to estimate the pathogenicity risk of HPV 39 variants in this population.

The prevalence of human herpesvirus 8 in normal, premalignant, and malignant cervical samples of Iranian women

Abstract Background Regard to this fact that the main transmission route of HPV and HHV-8 is via sexual activity, it is reasonable to speculate that coinfection of HPV and HHV-8 may have been played an important role in the development of cervical cancer. The aim of this study was to estimate the prevalence of HHV-8 and the frequency of HPV and HHV-8 coinfection in cervical samples of patients with cervical cancer and healthy individuals. Methods In total, 364 samples from 61 patients with cervical cancer, 124 women with premalignant lesions, and 179 healthy individuals were investigated by nested-PCR. Results The frequency of HHV-8 was found to be 22.9%, 17.7%, and 14.5% in cervical cancer, premalignant lesions, and normal specimens, respectively (P = 0.308). The overall prevalence of coinfection between HHV-8 and HPV was shown to be 16.2%. The HPV prevalence was higher in HHV-8 positive samples than HHV-8 negative specimens in all three studied groups and this difference was reached a statistically significant level (P = 0.002). However, no significant differences were found between HHV-8 positivity and HPV genotypes (P = 0.08). Conclusions Our results showed the higher rate of HHV-8 genome detection in cervical cancer group than control group. However, future studies with larger sample sizes and evaluation of expression of HHV-8 proteins are warranted.

Characteristics of human papillomavirus infection among women with cervical cytological abnormalities in the Zhoupu District, Shanghai City, China, 2014–2019

Abstract Background Human papillomavirus (HPV) infection is currently the main cause of cervical cancer and precancerous lesions in female patients. By analyzing 6-year patient data from Shanghai Zhoupu Hospital in China, we retrospectively analyzed the epidemiological characteristics of women to determine the relationship between HPV genotype and cytological test results. Methods From 2014 to 2019, 23,724 cases of cervical shedding were collected from Zhoupu Hospital in Shanghai, China. By comparing the results of HPV and ThinPrep cytology test (TCT), the HPV infection rate of patients was retrospectively analyzed. HPV genotyping using commercial kits can detect 21 HPV subtypes (15 high-risk and 6 low-risk). According to the definition of the Bethesda system, seven types of cervical cytology results were involved. Results 3816 among 23,724 women, nearly 16.08%, were infected with HPV. The top three highest HPV prevalence rates were high-risk type infection, including HPV52 (3.19%), 58 (2.47%) and 16 (2.34%). The number of single-type HPV infections (3480 (91.20%)) was much larger than the number of multi-type ones (336 (8.8%)). Single-type infections were mainly in women aged 50–60 (16.63%) and women under 30 (15.37%), while multi-type infections were more common in women over 60 (2.67%). By analyzing the long-term trends, between 2014 and 2019, HPV52, 58, and 16 subtypes changed significantly, and the HPV positive rate also changed significantly during this period. Among 4502 TCT positive women, 15 (4.04%), 125 (2.64%),159 (1.54%), 4202 (17.71%) and 1 (0.004%) had atypical glandular cells (AGC), high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL), atypical squamous cells (ASC)and cervical adenocarcinoma, respectively. The HPV infection rates were 66.08%, 63.99%, 115.20%, 119.50%, and 31.72% for NILM, AGCs, HSILs LSILs and ASCs, respectively. Conclusions HPV and TCT screening were very important steps in the secondary prevention of cervical cancer. Through the tracking and analysis of HPV and TCT results in this study, it can provide valuable information for Shanghai's HPV screening and prevention strategies, and provide references for clinical decision-making in the treatment of cervical cancer and precancerous lesions.

Establishment of early diagnosis models for cervical precancerous lesions using large-scale cervical cancer screening datasets

Abstract Background Human papilloma virus (HPV) DNA test was applied in cervical cancer screening as an effective cancer prevention strategy. The viral load of HPV generated by different assays attracted increasing attention on its potential value in disease diagnosis and progression discovery. Methods In this study, three HPV testing datasets were assessed and compared, including Hybrid Capture 2 (n = 31,954), Aptima HPV E6E7 (n = 3269) and HPV Cobas 4800 (n = 13,342). Logistic regression models for diagnosing early cervical lesions of the three datasets were established and compared. The best variable factor combination (VL + BV) and dataset (HC2) were used for the establishment of six machine learning models. Models were evaluated and compared, and the best-performed model was validated. Results Our results show that viral load value was significantly correlated with cervical lesion stages in all three data sets. Viral Load and Bacterial Vaginosis were the best variable factor combination for logistic regression model establishment, and models based on the HC2 dataset performed best compared with the other two datasets. Machine learning method Xgboost generated the highest AUC value of models, which were 0.915, 0.9529, 0.9557, 0.9614 for diagnosing ASCUS higher, ASC-H higher, LSIL higher, and HSIL higher staged cervical lesions, indicating the acceptable accuracy of the selected diagnostic model. Conclusions Our study demonstrates that HPV viral load and BV status were significantly associated with the early stages of cervical lesions. The best-performed models can serve as a useful tool to help diagnose cervical lesions early.

HPV 16 E7 alters translesion synthesis signaling

AbstractA subset of human papillomaviruses (HPVs) are the cause of virtually every cervical cancer. These so-called “high-risk” HPVs encode two major oncogenes (HPV E6 and E7) that are necessary for transformation. Among "high-risk” HPVs, HPV16 causes most cervical cancers and is often used as a representative model for oncogenic HPVs. The HPV16 E7 oncogene facilitates the HPV16 lifecycle by binding and destabilizing RB, which ensures the virus has access to cellular replication machinery. RB destabilization increases E2F1-responsive gene expression and causes replication stress. While HPV16 E6 mitigates some of the deleterious effects associated with this replication stress by degrading p53, cells undergo separate adaptations to tolerate the stress. Here, we demonstrate that this includes the activation of the translesion synthesis (TLS) pathway, which prevents replication stress from causing replication fork collapse. We show that significantly elevated TLS gene expression is more common in cervical cancers than 15 out of the 16 the other cancer types that we analyzed. In addition to increased TLS protein abundance, HPV16 E7 expressing cells have a reduced ability to induct a critical TLS factor (POLη) in response to replication stress-inducing agents. Finally, we show that increased expression of at least one TLS gene is associated with improved survival for women with cervical cancer.

Whole-genome analysis of human papillomavirus 67 isolated from Japanese women with cervical lesions

AbstractBackgroundHuman papillomavirus (HPV) type 67 is phylogenetically classified intoAlphapapillomavirusspecies 9 (alpha-9) together with other carcinogenic types (HPV16, 31, 33, 35, 52 and 58), but is the only alpha-9 type defined as possibly carcinogenic. This study aimed to determine whole-genome sequences of HPV67 isolated from Japanese women with cervical cancer or cervical intraepithelial neoplasia (CIN) to better understand the genetic basis of the oncogenic potential of HPV67.MethodsTotal cellular DNA isolated from cervical exfoliated cells that were single positive for HPV67 (invasive cervical cancer, n = 2; CIN3, n = 6; CIN 2, n = 1; CIN1, n = 2; the normal cervix, n = 1) was subjected to PCR to amplify HPV67 DNA, followed by next generation sequencing to determine the complete viral genome sequences. Variant lineages/sublineages were assigned through viral whole-genome phylogenetic analysis. The transcriptional activity of the virus early promoter was assessed by luciferase reporter assays in cervical cancer cell lines.ResultsPhylogenetic analyses of HPV67 genomes from Japan (n = 12) revealed that 11 belonged to lineage A (sublineage A1, n = 9; sublineage A2, n = 2) and one belonged to lineage B. All cancer cases contained sublineage A1 variants, and one of these contained an in-frame deletion in theE2gene. The long control region of the HPV67 genome did not induce transcription from the virus early promoter in HeLa cells, but showed weak transcriptional activity in CaSki cells.ConclusionsThe single detection of HPV67 in cervical cancer and precancer specimens strongly suggests the carcinogenic potential of this rare genotype. The phylogenetic analysis indicates a predominance of lineage A variants among HPV67 infections in Japan. Since only 23 complete genome sequences of HPV67 had been obtained until now, the newly determined genome sequences in this study are expected to contribute to further functional and evolutionary studies on the genetic diversity of HPV67.

A unique Levey–Jennings control chart used for internal quality control in human papillomavirus detection

Abstract Objective The purpose of this study was to provide an updated estimate of the prevalences of different types of human papillomavirus (HPV) in females in Chaoshan District and to establish an internal quality control (IQC) method for excluding false-positive results in HPV detection by using the Levey–Jennings control chart. Method HPV types were detected in 23,762 cervical samples by using PCR membrane hybridization. The means and standard deviations (SDs) of the positive rates were calculated, the Levey–Jennings chart was plotted, and the rules for “out of control” and “warning” were established. A set of standardized IQC for HPV DNA tests was developed based on the values and Levey–Jennings charts. Result In 466 batches, the positive rate exceeded the 1 + 2SD rule 24 times, but there was no consecutive exceedance, which was considered “in control”. When the positive rate exceeded the 1 + 3SD rule 8 times with consecutive exceedance, it was considered “out of control”. Further examination revealed that detections showing “out of control” had an undesirable random error, indicating that contamination may occur due to improper operation. Conclusion This unique Levey–Jennings control chart is a practical method for eliminating false-positive results in HPV DNA detection and should be widely applicable in molecular diagnostic laboratories.

Human papillomavirus prevalence and genotype distribution landscapes in Shannan City, Tibet Tibetan Autonomous Region, China

Abstract Background Data regarding human papillomavirus (HPV) prevalence and genotype distribution are limited in Shannan City, Tibet Tibetan Autonomous Region, China. The purpose of this study is to provide reliable data for guiding women in Shannan City in cervical cancer screening and HPV vaccine innoculation. Methods HPV testing was performed on women aged 16–109 years (mean age 44.03 ± 9.25 years) from Shannan City in 2019 and 2020, which was implemented technically by gynecological examination, vaginal discharge smear microscopy, cytology, and HPV detection. The overall prevalence, age-specific prevalence, and genotype distribution were analyzed. Results A total of 48,126 women received HPV testing, of which 3929 were detected human papillomavirus. The HPV-positive rate was 8.16% (3929/48,126), and the highest prevalence was in the ≤ 25-year-old age group (12.68%). After the age of 25, the prevalence rate decreased rapidly, and then slowly increased from 7.49% in the 46–55 age group to 9.82% in the ≥ 66 age group, showing a “U-shaped” pattern. The positive prevalence of HPV 16 or 18-only was 1.43%, that of other HPV genotypes except HPV 16 or 18 was 6.39%, and mixed HPV infections including HPV 16 or 18 was 0.34%. Conclusions The HPV infection rate in Shannan city is rather low, and the age-specific prevalence of HPV infection presents a “U” curve, suggesting the importance of screening among younger women and the necessity of detection among older women.

Human papillomavirus E6E7 mRNA and TERC lncRNA in situ detection in cervical scraped cells and cervical disease progression assessment

Abstract Background Human papillomavirus screen in female cervical cells has demonstrated values in clinical diagnosis of precancerous lesions and cervical cancers. Human papillomavirus tests of cervical cells by utilizing Polymerase Chain Reaction (PCR) method provides human papillomavirus infection status however no further virus in situ information. Although it is well known that the tests of human papillomavirus E6/E7 RNA location in infected cervical cells and cell internal malignancy molecular will provide clues for gynecologists to evaluate disease progression, there are technique difficulties to preserve RNAs in cervical scraped cells for in situ hybridization. Methods In current study, after developing a cervical cell collection and preparation method for RNA in situ hybridization, we captured the chance to screen 98 patient cervical cell samples and detected human papillomavirus E6/E7 mRNAs of high-risk subtypes, low-risk subtypes and long non-coding RNA (lncRNA) TERC in the cells. Results There were 69 samples exhibited consistence between human papillomavirus PCR and human papillomavirus RNA in situ hybridization results in cervical collected cells. Among them, 23 were both positive and 46 were both negative. In the rest 29 samples, 8 were HPV RNAscope positive, either high risk or low risk subtypes, however HPV PCR negative. Another 9 samples were HPV PCR results positive whereas RNAscope negative. The last 12 samples were HPV positive detected by both RNAscope and PCR methods, however inconsistent between high-risk and low-risk subtypes. In RNAscope positive samples, viral E6/E7 mRNAs were observed to distribute in cervical scraped cell nucleus and cytoplasm. Moreover, HPV viral RNA gathered clusters were observed outside of cells through human papillomavirus RNA in situ hybridization detection. Varied numbers of human papillomavirus infective cells were detected by RNAscope assay in different patients even though they were all human papillomavirus high-risk subtype positive discovered by human papillomavirus PCR results. A cell malignancy related long non-coding RNA, TERC, has been detected in seven patient samples. The patient follow-up information was further analyzed with RNAscope results which indicated a combination of RNAscope positive signals of TERC and human papillomavirus high risk signals in more than 10 cells (cytoplasm or nucleus) may connect with cervical lesion fast progression which deserves further studies in the future.C Conclusions Taken together, current study has provided an observable clue for gynecologists to evaluate human papillomavirus infection stage and cell malignancy status which may contribute for assessment of cervical disease progression.

Temporal changes in the vaginal microbiota in self-samples and its association with persistent HPV16 infection and CIN2+

Abstract Background The vaginal microbiota has been reported to be associated with HPV infection and cervical cancer. This study was performed to compare the vaginal microbiota at two timepoints in women performing self-sampling and had a persistent or transient HPV16 infection. The women were tested for 12 high-risk HPV (hrHPV) types but only women with single type (HPV16) were included to reduce confounding variables. Methods In total 96 women were included in this study. Of these, 26 were single positive for HPV16 in the baseline test and HPV negative in the follow-up test and 38 were single positive for HPV16 in both tests and diagnosed with CIN2+ in histology. In addition, 32 women that were negative for all 12 HPV tested were included. The samples of vaginal fluid were analyzed with the Ion 16S™ Metagenomics Kit and Ion 16S™ metagenomics module within the Ion Reporter™ software. Results K-means clustering resulted in two Lactobacillus-dominated groups, one with Lactobacillus sp. and the other specifically with Lactobacillus iners. The two remaining clusters were dominated by a mixed non-Lactobacillus microbiota. HPV negative women had lower prevalence (28%) of the non-Lactobacill dominant cluster in the baseline test, as compared to women with HPV16 infection (42%) (p value = 0.0173). Transition between clusters were more frequent in women with persistent HPV16 infection (34%) as compared in women who cleared the HPV16 infection (19%) (p value = 0.036). Conclusions The vaginal microbiota showed a higher rate of transitioning between bacterial profiles in women with persistent HPV16 infection as compared to women with transient infection. This indicate an instability in the microenvironment in women with persistent HPV infection and development of CIN2+.

Prevalence of human papillomavirus genotypes and precancerous cervical lesions in a screening population in Beijing, China: analysis of results from China’s top 3 hospital, 2009–2019

Abstract Background Cervical cancer is the fourth most common cancer in women. Early detection and diagnosis play an important role in secondary prevention of cervical cancer. This study aims to provide more information to develop an effective strategy for the prevention and control of cervical cancer in northern China. Methods A retrospective single-centre descriptive cross-sectional study was conducted in Chinese PLA General Hospital located in Beijing, covering the period from January 2009 to June 2019. The patients who underwent a polymerase chain reaction (PCR)-based HPV genotyping test and cervical pathological diagnosis were included. Furthermore, we limited the interval between the two examination within 180 days for the purpose of making sure their correlation to analyse their relationship. Moreover, the relationship between different cervical lesions and age as well as single/multiple HPV infection was assessed. Results A total of 3134 patients were eligible in this study after HPV genotyping test and pathological diagnosis. Most of the patients (95%) were from northern China. Among the patients, 1745(55.68%) had high-grade squamous intraepithelial neoplasia (HSIL), 1354 (43.20%) had low-grade squamous intraepithelial neoplasia (LSIL) and 35 (1.12%) were Normal. The mean age was 42.06 ± 10.82(range, 17–79 years). The women aged 35–49 years accounted for the highest incidence rate. The top five most commonly identified HPV genotypes in each lesion class were as follows: HPV16, 58, 52, 31 and 51 in the class of HSIL; HPV16, 52, 58, 56 and 51 in the class of LSIL; HPV16, 31, 6,11, 52 and 58 in the class of normal. The frequencies of HPV single genotype infection and multiple genotypes infection were 55.26 and 34.18%, respectively. There was no difference in the attributable proportions of multiple genotypes infection amongst HSIL, LSIL and Normal. Conclusions In Northern China, HPV16 was the most dominant genotype in the patients with pathological examination. The peak age of the onset of HSIL was between 35 and 49 years of age. Infection with multiple HPV genotypes did not increase the risk of HSIL. Type-specific HPV prevalence and attribution proportion to cervical precancerous lesions should be taken into consideration in the development of vaccines and strategy for screening in this population.

Prevalence characteristics of cervical human papillomavirus (HPV) infection in the Zhoupu District, Shanghai City, China

Abstract Background Human papillomavirus (HPV) infection is the leading cause of genital diseases. It can cause a series of cervical lesions. The distribution of HPV genotypes indicates that the increased prevalence of high-risk HPV (HR-HPV) is positively correlated with the severity of cervical lesions. In addition, persistent HR-HPV infection is associated with the risk of cervical cancer. Considering the latest approval of homemade HPV vaccine in China and the prevalence of HPV distribution, this is of great significance for guiding HPV vaccination work. Objective Our study’s purpose was to examine trends of cervical HPV infection rate in each 5-year age group from 2011 to 2019. Methods Retrospective analysis of human papillomavirus prevalence rate of 59,541 women from 2011 to 2019 in the District Zhoupu of Shanghai City in China. HPV genotype testing is performed using a commercial kit designed to detect 15 high-risk HPV genotypes and 6 low-risk HPV genotypes. Trends were examined for each 5-year age group. Results In the District Zhoupu of Shanghai City in China, the prevalence rate of cervical HPV increased significantly among women aged 15–34 years. The most prevalent HR-HPV genotypes were 52, 16, 58, 53, 39, and 51. Conclusion Cervical HPV prevalence rate is very high in younger women in suburb Shanghai. Due to significant differences in infection rates between specific age groups and HPV subtypes, timely intervention is required for these vulnerable populations.

Human myoma tissue-based extracellular matrix models for testing the effects of irradiation on the HPV positive cells

Abstract Background This study was designed to investigate the invasion of human papillomavirus (HPV) positive human cervical carcinoma cell lines in human leiomyoma-based extracellular matrices in vitro, and to test the suitability of the model for studying the irradiation effects on the cancer cell invasion. Methods HPV positive cervical carcinoma cell lines SiHa and CaSki, and HPV negative squamous cell carcinoma cell line HSC-3 were used. CaSki cells contain around 600 copies of HPV 16 virus in the genome, whereas SiHa have only 1–2 copies per cell. Cells were analyzed using two different human tumor derived extracellular matrix methods (3D myoma disc model, and Myogel Transwell invasion assay). Cultures were irradiated with 4 Gy. Myoma invasion area and the depth of invasion were measured with ImageJ 1.51j8 software. Statistical analyses were performed with SPSS Statistics (IBM SPSS® Statistics 25). Results All cells invaded through Myogel coated Transwell membranes and within myoma discs. In myoma discs, a difference in the invasion depth (p = 0.0001) but not in invasion area (p = 0.310) between the HPV positive cell lines was seen, since SiHa (less HPV) invaded slightly better than CaSki (more HPV). HSC-3 cells (HPV negative) invaded deepest (p = 0.048) than either of the HPV positive cell line cells. No difference was detected in the invasion area (p = 0.892) between HPV positive and HPV negative cells. The ionized radiation significantly reduced the invasion depth of HSC-3 (p = 0.008), SiHa (p = 0.0001) and CaSki (p = 0.005). No significant effect on the invasion area was detected in any of the cell lines. However, a significant difference was observed between SiHa and CaSki in the reduction of the invasion depth after radiation (p = 0.013) as the reduction was greater with SiHa than CaSki. Conclusions Both solid and gelatinous human leiomyoma-based extracellular matrix models were suitable platforms to study the invasion of HPV positive cervical carcinoma cells in vitro. SiHa cells with less HPV copy number cells invaded slightly better and were slightly more sensitive to irradiation than CaSki cells with high HPV copy number. However, there was no drastic differences between the invasion properties of these carcinoma cells.

Human immunodeficiency virus is a driven factor of human papilloma virus among women: evidence from a cross-sectional analysis in Yaoundé, Cameroon

Abstract Background Human papillomavirus (HPV) is the leading cause of cervical cancers, causing 270.000 deaths annually worldwide of which 85% occur in developing countries with an increasing risk associated to HIV infection. This study aimed at comparing HPV’s positivity and genotype distribution in women according to their HIV status and determinants. Methods A comparative study was carried out in 2012 at the Chantal BIYA International Reference Centre (CIRCB) among 278 women enrolled consecutively at the General Hospital and the Gynaeco-Obstetric and Paediatric Hospital of the City of Yaoundé. HPV genotyping was performed by real-time PCR, HIV serological screening by serial algorithm, CD4 T cell phenotyping by flow cytometry and HIV viral load by Abbott m2000RT. Statistical analyses were performed using Microsoft Excel 2016 and Graph Pad version 6.0 software; with P  &lt; 0.05 considered statistically significant. Results Globally, mean age was 37 ± 3 years; median CD4-count for HIV+ was 414 cells/mm 3 [IQR: 264.75–588] and median viremia was 50 RNA copies/mL [IQR: &lt; 40–8288]. Overall HPV rate was 38.49% (107/278); 58.88% for single women vs. others (28.97% married, 2.80% divorced, 9.34% for widows), OR: 2.164; p  = 0.0319. Following HIV status, HPV rate was 43.48% (80/184) among HIV+ vs. 28.72% (27/94) among HIV- (OR: 1.937; p  &lt; 0.0142); HPV genotypes among HIV+ vs. HIV- were respectively distributed as follows: genotype 16 (3.75% vs. 0.00%, p  = 0.57), genotype 18 (3.75% vs. 3.70%, p  = 1.00), co-infection 16 and others (8.75% vs. 7.40%, p  = 1.00), co-infection 18 and others (8.75% vs. 11.11%, p  = 0.71), co-infection 16, 18 and others (2.50% vs. 0.00%, p = 1.00) and other genotypes (72.50% vs. 77.78%, p  = 0.80). Among HIV+ participants, HPV rate following CD4 was 62.88% (61/97) for CD4 &lt; 500 vs. 35.71% (20/56) for CD4 ≥ 500 (OR: 3.05; p  = 0.0012) while HPV rate following HIV viremia was 42.71% (41/96) with &lt; 1000 RNA copies/ml vs. 66.00% (33/50) with &gt; 1000 RNA copies/ml (OR = 0.384; p  = 0.009). Conclusion In Yaoundé, HPV rate appear to be very high, with higher rates of genotypes other than 16 and 18. In the event of HIV infection, the risk of HPV positivity is two times higher, favoured essentially by immunodeficiency. Thus, HIV-infected women should be closely monitored to prevent the emergence of cervical cancer.

Enhanced disease progression due to persistent HPV-16/58 infections in Korean women: a systematic review and the Korea HPV cohort study

AbstractBackgroundPersistent human papillomavirus (HPV) infection is a key factor for the development and progression of cervical cancer. We sought to identify the type-specific HPV prevalence by cervical cytology and assess disease progression risk based on high-risk persistent HPV infection in South Korea.MethodsTo investigate the HPV prevalence by Pap results, we searched seven literature databases without any language or date restrictions until July 17, 2019. To estimate the risk of disease progression by HPV type, we used the Korea HPV Cohort study data. The search included the terms “HPV” and “Genotype” and “Korea.” Studies on Korean women, type-specific HPV distribution by cytological findings, and detailed methodological description of the detection assay were included. We assessed the risk of disease progression according to the high-risk HPV type related to the nonavalent vaccine and associated persistent infections in 686 HPV-positive women with atypical squamous cells of uncertain significance or low-grade squamous intraepithelial lesions from the Korea HPV Cohort Study. Type-specific HPV prevalence was the proportion of women positive for a specific HPV genotype among all HPV-positive women tested for that genotype in the systematic review.ResultsWe included 23 studies in our review. HPV-16 was the most prevalent, followed by HPV-58, -53, -70, -18, and -68. In women with high-grade squamous intraepithelial lesions, including cancer, HPV-16, -18, and -58 were the most prevalent. In the longitudinal cohort study, the adjusted hazard ratio of disease progression from atypical squamous cells of uncertain significance to high-grade squamous intraepithelial lesions was significantly higher among those with persistent HPV-58 (increase in risk: 3.54–5.84) and HPV-16 (2.64–5.04) infections.ConclusionsWhile HPV-16 was the most prevalent, persistent infections of HPV-16/58 increased the risk of disease progression to high-grade squamous intraepithelial lesions. Therefore, persistent infections of HPV-16 and -58 are critical risk factors for cervical disease progression in Korea. Our results suggest that equal attention should be paid to HPV-58 and -16 infections and provide important evidence to assist in planning the National Immunization Program in Korea.

Enhanced synergistic antitumor effect of a DNA vaccine with anticancer cytokine, MDA-7/IL-24, and immune checkpoint blockade

Abstract Background MDA-7/IL-24 cytokine has shown potent antitumor properties in various types of cancer without exerting any significant toxicity on healthy cells. It has also been proved to encompass pro-immune Th1 cytokine-like behavior. Several E7 DNA vaccines have developed against human papillomavirus (HPV)-related cervical cancer. However, the restricted immunogenicity has limited their clinical applications individually. To address this deficiency, we investigated whether combining the E7 DNA vaccine with MDA-7/IL-24 as an adjuvant would elicit efficient antitumor responses in tumor-bearing mouse models. Next, we evaluated how suppression of immunosuppressive IL-10 cytokine would enhance the outcome of our candidate adjuvant vaccine. Methods For this purpose, tumor-bearing mice received either E7 DNA vaccine, MDA-7/IL-24 cytokine or combination of E7 vaccine with MDA-7/IL-24 adjuvant one week after tumor challenge and boosted two times with one-week interval. IL-10 blockade was performed by injection of anti-IL-10 mAb before each immunization. One week after the last immunization, mice were sacrificed and the treatment efficacy was evaluated through immunological and immunohistochemical analysis. Moreover, the condition of tumors was monitored every two days for six weeks intervals from week 2 on, and the tumor volume was measured and compared within different groups. Results A highly significant synergistic relationship was observed between the E7 DNA vaccine and the MDA-7/IL-24 cytokine against HPV-16+ cervical cancer models. An increase in proliferation of lymphocytes, cytotoxicity of CD8+ T cells, the level of Th1 cytokines (IFN-γ, TNF-α) and IL-4, the level of apoptotic markers (TRAIL and caspase-9), and a decrease in the level of immunosuppressive IL-10 cytokine, together with the control of tumor growth and the induction of tumor regression, all prove the efficacy of adjuvant E7&amp;IL-24 vaccine when compared to their individual administration. Surprisingly, vaccination with the DNA E7&amp;IL-24 significantly reduced the population of Regulatory T cells (Treg) in the spleen of immunized mice compared to sole administration and control groups. Moreover, IL-10 blockade enhanced the effect of the co-administration by eliciting higher levels of IFN-γ and caspase-9, reducing Il-10 secretion and provoking the regression of tumor size. Conclusion The synergy between the E7 DNA vaccine and MDA-7/IL-24 suggests that DNA vaccines’ low immunogenicity can be effectively addressed by coupling them with an immunoregulatory agent. Moreover, IL-10 blockade can be considered a complementary treatment to improve the outcome of conventional or novel cancer therapies.

Possible role of negative human papillomavirus E6/E7 mRNA as a predictor of regression of cervical intraepithelial neoplasia 2 lesions in hr-HPV positive women

Abstract Background The aim of this study was to evaluate the regression rate of CIN2 p16 positive lesions in women over 25 years of age and identify possible predictors of regression. Methods A total of 128 CIN2 p16 positive patients over 25 years old were considered. The women met the following inclusion criteria: HPV genotype 16, 18, 31, 33, 45 positive, HPV E6 / E7 mRNA test positive, without immune system pathologies, not pregnant and had completed at least two years of follow-up. At each follow-up examination patients were examined by colposcopy, HPV test, E6/E7mRNA, targeted biopsy and p16 protein detection. The final state after the two years of follow-up was classified as progression if the histology showed a CIN3, persistence if the lesion was a CIN2, regression if negative or LSIL. The predicted regression factors evaluated were: HPV E6/E7mRNA, protein p16. Results Overall, we had 35.1% (45 cases) of progression to CIN3, 41.4% (53 cases) of persistence and 23.4% (30 cases) of regression. The regression rate was higher in women with negative mRNA 92.8% (26/28), OR 312 (34.12–1798.76) p = 0.0001, while women with p16 negative had a regression of 22.6% (7/31), OR 0.94 (95% CI 0.36–2.46), p was not significant. We found no significant difference in regression between p16 positive (23.7%) and p16 negative (22.6%) CIN2 p16 lesions. p16 had a VPN of 22.6 (CI 95% 0.159–0.310), indicating that a p16 negative lesion does not exclude a CIN2 + . Conclusions We had a regression rate of 23.4%, which was low if we consider that in the literature the regression rates vary from 55 to 63%. The discrepancy in the results may indeed be explained by the fact that all lesions in our study were hr-HPV positive and belonged to “older women” reflecting a more "high-risk" population. As regression factors we studied p16 and HPV E6/E7 mRNA. The results of our study show that HPV mRNA, if negative, appears to be able to identify CIN2 lesions with a higher probability of regression and underlines how a p16 negative is not an indicator of regression.

Genetic variability of E6 and E7 genes of human papillomavirus type 58 in Jingzhou, Hubei Province of central China

Abstract Background Cervical cancer is a common malignant tumor in women, with a high mortality rate, has great harm to women’s health. Long-term and persistent infection of high-risk human papillomavirus (HR-HPV) is the main reason of the occurrence and development of cervical cancer. Methods The infection rate of HPV-58 is higher in the Jingzhou area. In this study, 172 complete HPV-58 E6-E7 sequences were amplified by polymerase chain reaction (PCR), the amplified products were sequenced, and the gene variations of HPV-58 E6-E7 were analyzed. A Neighbor-Joining phylogenetic tree was constructed by MEGA 11. The secondary structure of E6 and E7 protein was investigated. PAML X was used to analyze the selective pressure. The B cell epitopes of E6 and E7 proteins in HPV-58 were predicted by ABCpred server. Results In E6 sequences, 10 single nucleotide variants were observed, including 7 synonymous and 3 non-synonymous variants. In E7 sequences, 12 single nucleotide variants were found, including 3 synonymous variants and 9 non-synonymous variants. There are 5 novel variants. The phylogenetic analysis showed that all the E6-E7 sequences were distributed in A lineage. No positively selected site was found in E6 sequence, but G63 in E7 sequences was identified as positively selected site. Some amino acid substitutions affected multiple B cell epitopes. Conclusion Various E6 and E7 mutational data may prove useful for development of better diagnostic and vaccines for the region of Jingzhou, Hubei province of central China.

Prevalence and distribution of human papillomavirus (HPV) in Luoyang city of Henan province during 2015–2021 and the genetic variability of HPV16 and 52

Abstract Background Persistent high-risk Human papillomavirus (HPV) subtypes infection has been implicated as a causative of cervical cancer. Distribution and genotypes of HPV infection among females and their variations would assist in the formulation of preventive strategy for cervical cancer. The purpose of the present study is to investigate the prevalence of HPV among females in central China. Methods The distribution and genotypes of HPV among 9943 females attending the gynecological examinations in central of China during 2015–2021 were investigated. HPV genotypes were detected using a commercial kit. Nucleotides sequences of L1, E6 and E7 genes in HPV16 or HPV52 positive samples collected in 2021 were amplified by polymerase chain reaction (PCR). Variations of L1, E6 and E7 in HPV16 and HPV52 were gained by sequencing and compared with the reference sequence. Sublineages of HPV16 and HPV52 were determined by the construction of phylogenetic tree based on L1 gene. Results The overall prevalence of HPV infection was 22.81%, with the infection rate of high-risk human papillomavirus (HR-HPV) was 19.02% and low-risk human papillomavirus (LR-HPV) was 6.40%. The most top five genotypes of HPV infection were HPV16 (7.49%), HPV52 (3.04%), HPV58 (2.36%), HPV18 (1.65%) and HPV51 (1.61%). Plots of the age-infection rate showed that the single HPV, multiple HPV, HR-HPV, LR-HPV infection revealed the same tendency with two peaks of HPV infection were observed among females aged ≤ 20 year-old and 60–65 year-old. The predominant sublineage of HPV16 was A1 and B2 for HPV52. For HPV16, The most prevalent mutations were T266A (27/27) and N181T (7/27) for L1, D32E for E6 and S63F for E7 in HPV16. For HPV52, all of the nucleotide changes were synonymous mutation in L1 (except L5S) and E7 genes. The K93R mutation was observed in most HPV52 E6 protein. Conclusions The present study provides basic information about the distribution, genotypes and variations of HPV among females population in Henan province, which would assist in the formulation of preventive strategies and improvements of diagnostic probe and vaccine for HPV in this region.

Human papillomavirus genotype distribution in Ethiopia: an updated systematic review

Abstract Background Cervical cancer is caused by infection with high-risk human papillomaviruses (HR-HPVs). It is one of the leading causes of cancer-related deaths in Ethiopia and globally. To develop efficient vaccination and HPV-based cervical cancer screening approaches, data on genotype distribution of HPVs is crucial. Hence, the study was aimed to review HPV genotype distribution in Ethiopia. Methods Research articles were systematically searched using comprehensive search strings from PubMed/Medline and SCOPUS. Besides, Google Scholar was searched manually for grey literature. The last search was conducted on 18 August 2021. The first two authors independently appraised the studies for scientific quality and extracted the data using Excel sheet. The pooled HPV genotype distribution was presented with descriptive statistics. Results We have included ten studies that were reported from different parts of the country during 2005 and 2019. These studies included 3633 women presented with different kinds of cervical abnormalities, from whom 29 different HPV genotypes with a sum of 1926 sequences were reported. The proportion of high-risk, possible/probable high-risk and low-risk HPVs were at 1493 (77.5%), 182 (9.4%) and 195 (10.1%), respectively. Of the reported genotypes, the top five were HPV 16 (37.3%; 95% CI 35.2.1–39.5%), HPV 52 (6.8%; 95% CI 5.8–8.0%), HPV 35 (4.8%; 95% CI 3.9–5.8%), HPV 18 (4.4%; 95% CI 3.5–5.3%) and HPV 56 (3.9%: 95% CI 3.1–4.9%). Some of other HR-HPV groups include HPV 31 (3.8%), HPV 45 (3.5%), HPV 58 (3.1%), HPV 59(2.3%), and HPV 68 (2.3%). Among the high-risk types, the combined prevalence of HPV 16/18 was at 53.7% (95% CI 51.2–56.3%). HPV 11 (2.7%: 95% CI 2.1–3.5%), HPV 42 (2.1%: 95% CI 1.5–2.8%) and HPV 6 (2.1%: 95% CI 1.4–2.7%) were the most common low-risk HPV types. Conclusions We noted that the proportion of HR-HPV types was higher and HPV 16 in particular, but also HPV 52, HPV 35 and HPV 18, warrant special attention in Ethiopian’s vaccination and HPV based cervical screening program. Additional data from other parts of the country where there is no previous HPV genotype report are needed to better map the national HPV genotypes distribution of Ethiopia.

Prevalence and distribution of human papillomavirus genotypes among women attending gynecology clinics in northern Henan Province of China

Abstract Background Human papillomavirus (HPV) infection can cause cervical and other cancers, including vulva, vagina, penis, anus, or oropharynx. However, in China's northern Henan Province, data on the prevalence and genotype distribution of HPV among women attending gynecology clinics is limited. This study aimed to investigate the current prevalence and genotype distribution of HPV among women attending gynecology clinics in northern Henan Province. Methods This study included 15,616 women aged 16–81 years old who visited the Xinxiang central hospital's gynecology department between January 2018 and December 2019. HPV DNA was detected by a conventional PCR method followed by HPV type-specific hybridization, which was designed to detect 17 high-risk HPV (HR-HPV) genotypes and 20 low-risk HPV (LR-HPV) genotypes. HPV prevalence and corresponding 95% confidence intervals (95% CI) were calculated using SPSS 18.0. Results The overall HPV prevalence was 19.7% among women in northern Henan Province. Single, double, and multiple HPV infections accounted for 13.7%, 4.3%, and 1.8% of the total cases. Most infections were caused by HR-HPV (71.8%), and single genotype HPV infection (13.7%) was the most common pattern. The most common HR-HPV genotype was HPV16 (4.3%), followed by HPV52 (3.5%) and HPV58 (2.0%). The most common LR-HPV genotype was HPV6 (1.4%), followed by HPV61 (1.1%) and HPV81 (1.1%). Conclusions HPV infection is high among women attending gynecology clinics in northern Henan Province. The highest prevalence was found in women less than 20 years old. In northern Henan Province, the 9-valent HPV vaccine is strongly recommended for regular immunization.