Objective: To evaluate the performance of point-of-care testing for cervical cancer and precancerous lesions screening. Methods: In September 2020, 197 and 273 women were selected by using simple random sampling method from "self-sampling" cohort and "physician-sampling" cohort established in Xiangyuan county, Shanxi Province, China, respectively. Cervical exfoliated cells were collected by women themselves or gynecologists. All samples were detected by POCT and women with positive result were directly referred for colposcopy. Subsequently, all the samples were detected by careHPV and PCR test. Colposcopy and punch biopsy were performed for women with POCT negative but careHPV or PCR test positive at another visit. Using histopathological diagnosis as the gold standard, we calculated sensitivity, specificity and drew the receiver operating characteristic (ROC) curves. The accuracy of POCT was analyzed and compared to that of careHPV and conventional PCR test in cervical cancer and precancerous lesions screening. Results: The median (Q₁ , Q₃) age of 470 women was 51 (45, 57) years old. Based on self-sampling, the sensitivity and specificity of POCT for CIN2+ were 100.00% (95%CI: 56.56%-100.00%) and 28.95% (95%CI: 22.97%-35.76%), respectively. Compared with POCT, POCT HPV16/18 test had similar sensitivity and higher specificity of 89.47% (95%CI: 84.30%-93.08%). Self-sampling POCT HPV16/18 test had an AUC of 0.947 (95%CI:0.910-0.985), which was higher than that of careHPV and PCR test. Physician-sampling POCT test had 100.00% sensitivity (95%CI: 64.57%-100.00%) and 55.85% specificity (95%CI: 49.83%-61.70%) for detecting CIN2+. POCT HPV16/18 test had lower sensitivity (71.43%, 95%CI: 35.90%-91.76%) and higher specificity (92.45%, 95%CI: 88.63%-95.06%). POCT HPV16/18 test generally showed similar AUC on both self-collected samples and clinician-collected samples (0.947 vs 0.819, P=0.217). Conclusion: POCT HPV16/18 test is an effective method with relatively high sensitivity and specificity for cervical cancer screening.
Cervical Intraepithelial Neoplasia/diagnosis* ; Colposcopy ; Early Detection of Cancer/methods* ; Female ; Human papillomavirus 16/genetics* ; Human papillomavirus 18 ; Humans ; Mass Screening/methods* ; Papillomaviridae ; Papillomavirus Infections/diagnosis* ; Point-of-Care Testing ; Pregnancy ; Sensitivity and Specificity ; Uterine Cervical Neoplasms

Objectives: To analyze the type and distribution characteristics of human papillomavirus (HPV) infection along with cervical cytology in middle-aged and elderly women in Guangxi and to provide a basis for the prevention and treatment of cervical cancer in elderly women. Methods: 21 subtypes of HPV and cervical cytology of women over 45-year-old visiting the First Affiliated Hospital of Guangxi Medical University from January 2019 to December 2020 were collected. They were divided into two groups by age, 45-64 years group and over 65 years group. The HPV, HR-HPV, and multiple HPV infection prevalence were analyzed, as well as HPV genotypes, the age distribution of HPV infection rate, and cervical cytology. Results: A total of 6 657 eligible women were included. 6 238 women were in the 45-64 years group, with a HPV prevalence about 20.86% (1 301), while 419 women were in the over 65 years group, with a HPV prevalence about 32.94% (138). The age-associated HPV and HR-HPV prevalence increased with the age, peaking at the age group of 70-74 years (P<0.001). The most prevalent genotype was HPV52, and the infection rate was 5.3% (353), followed by HPV16 and HPV 58, about 4.63% (308) and 3.08% (205) respectively. The majority cytology of HPV-positive middle-aged and elderly women was normal. 8.70% (88) of them were ASC-US, 6.52% (66) for HSIL, 4.55% (46) for LSIL, and 2.96% (30) for ASC-H, and 0.10% (1) for SCC. Compared to middle-aged women, elderly women had a lower negative cytology rate, 69.79% (67) vs. 77.95% (714), but a higher HSIL rate, 13.54% (13) vs. 5.79% (53) (P<0.05). Conclusions: HPV and HR-HPV prevalence of elderly women in a medical center of Guangxi are higher than those of middle-aged women. The most prevalent genotype is HPV16 in elderly women, followed by HPV52 and HPV58.
Aged ; China/epidemiology* ; Female ; Hospitals ; Human papillomavirus 16 ; Humans ; Male ; Middle Aged ; Papillomaviridae/genetics* ; Papillomavirus Infections/genetics* ; Uterine Cervical Neoplasms

Objective: To examine the prevalence and frequencies of human papillomavirus (HPV) genotypes in cervical adenocarcinoma in situ (AIS). Methods: The cases of cervical AIS with concurrent tests of cytology and HPV typing from January 2007 to February 2020 in the Obstetrics and Gynecology Hospital of Fudan University were collected and analyzed. Results: A total of 478 cases of cervical AIS were obtained. The average age of the patients was 39.4 years (range, 19-81 years). The largest age group was 30-39 years (44.8%), followed by 40-49 years (34.7%). Among the 478 patients, 355 underwent high-risk HPV (hrHPV) testing and had a hrHPV-positive rate of 93.8%. Of the 355 patients, 277 also underwent HPV typing and were mostly positive for either or both HPV16 and HPV18 (93.1%), with 55.6% positive for HPV18 and 48.7% positive for HPV16. Among the 478 cases, 266 cases (55.6%) were diagnosed with both AIS and squamous intraepithelial lesion (SIL), while 212 cases (44.4%) were diagnosed with only AIS. Patients infected with HPV16 in the AIS and SIL group significantly outnumbered those in the AIS alone group (P<0.05). Moreover, the rate of positive cytology was 55.9% (167/299 cases), while that of negative cytology was 44.1% (132/299). Among the 109 patients with negative cytology results and co-tested hrHPV, there were 101 HPV-positive cases (92.7%), of which 88 cases were subject to HPV typing and showed an HPV16/18 positive rate of 94.3% (83/88 cases). Conclusions: The combination of HPV typing and cytological screening can maximize the detection rate of cervical AIS, and should continue to be utilized, ideally on a larger scale, in the future.
Adenocarcinoma in Situ/epidemiology* ; Adult ; Aged ; Aged, 80 and over ; Female ; Human papillomavirus 16/genetics* ; Human papillomavirus 18/genetics* ; Humans ; Middle Aged ; Papillomaviridae/genetics* ; Papillomavirus Infections/diagnosis* ; Prevalence ; Uterine Cervical Neoplasms/pathology* ; Young Adult

Objective: To investigate the correlation between methylation in human papillomavirus 16 (HPV16) long control region (LCR) and cervical intraepithelial neoplasia grade ≥2 (CIN2+). Methods: The literature retrieval was conducted by using the databases of PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang data and Weipu according to the inclusion and exclusion criteria, and the retrieval period was from the establishment of the databases to February 27^th, 2022. Software RevMan 5.3 and Stata 15.1 were used for Meta-analysis. Results: A total of 17 literatures were included involving 1 421 subjects. Results of Meta-analysis showed that OR of the correlation between methylation of HPV16 LCR and CIN2+ was 1.56 (95%CI: 0.70-3.47). Subgroup analysis showed that methylation of the 5' terminal, enhancer and promoter regions were not associated with CIN2+, while in four E2 binding sites (E2BS), the methylation of E2BS1, E2BS3 and E2BS4 increased the risk of CIN2+, with the ORs of 3.92 (95%CI: 1.92-7.99), 10.50 (95%CI: 3.67-30.04) and 3.65 (95%CI: 1.58-8.41), respectively. However, subgroup analysis on E2BS2 was not performed due to the limitation of the number of literatures. According to the different sources of population, the risk of CIN2+ in Chinese population was associated with methylation of HPV16 LCR (OR=2.14, 95%CI: 1.31-3.50). There was a correlation between the risk of CIN2+ and HPV16 LCR methylation in the population with pyrosequencing of HPV16 LCR, and OR was 1.75 (95%CI: 1.03-2.98). Conclusion: The risk of CIN2+ is correlated with the methylation of E2BS in HPV16 LCR, which can be used as potential biomarkers.
Female ; Humans ; Methylation ; Human papillomavirus 16/genetics* ; Asian People ; Uterine Cervical Neoplasms ; Uterine Cervical Dysplasia

To explore the molecular mechanism of human papillomavirus subtype 16(HPV-16)E7 oncogene-induced DNA re-replication in response to DNA damage. Flow cytometry was performed to examine the cell cycle changes in RPE1 E7 cells stably expressing HPV-16 E7 and its control cell RPE1 Vector after DNA damage.Immunoblotting assay was used to evaluate the early mitotic inhibitor 1(Emi1)expression in RPE1 E7 and RPE1 Vector cells with or without DNA damage.The changes of the proportion of polyploidy was detected by flow cytometry in DNA-damaged RPE1 E7 cells interfered by Emi1 small interfering RNA. Compared with the control cells,the proportion of polyploids in RPE1 E7 cells was significantly increased in response to DNA damage(=6.397,=0.0031).Emi1 protein expression was significantly increased in DNA damaged RPE1 E7 cells(=8.241,=0.0012).The polyploid ratio of RPE1 E7 cells was significantly reduced after Emi1 was interfered by two independent small interfering RNAs(=2.916,=0.0434;=3.452,=0.0260). In response to DNA damage,Emi1 promoted DNA re-replication caused by HPV-16 E7.
DNA Damage ; DNA Replication ; Human papillomavirus 16 ; Mitosis ; Oncogene Proteins, Viral

To investigate the DNA methylation in ZNF772 promoter region and its mRNA and protein expressions and analyze the clinical significance of DNA methylation of ZNF772 gene in cervical cancer. Cervical squamous cell carcinoma (SCC) tissues were harvested from three patients (SCC group),and normal cervical tissues from healthy individuals of the same age were used as the control group. Hyper-methylation and lower transcripts were screened by whole-genome bisulfite sequencing (WGBS) and RNA sequencing. Furthermore,in 40 cervical tissue samples in SCC group and 45 normal cervical tissues in the control group,DNA methylation status and mRNA expression of ZNF772 were measured by using real-time quantitative polymerase chain reaction (RT-qPCR) and bisulfite sequencing polymerase chain reaction (BSP). The protein expression was detected by immunohistochemistry. In the SCC group,the potential relationships of DNA methylation status in ZNF772 promoter and mRNA expression with the clinicopathological parameters of cervical cancer were analyzed. As shown by WGBS and RNA sequencing,the abnormal DNA methylated gene ZNF772 was associated with mRNA expression. RT-qPCR verified that the mRNA expression of ZNF772 was significantly lower in SCC group than in control group (=8.351,=0.016). Immunohistochemistry further confirmed that the positive expression of ZNF772 protein was down-regulated in SCC group (=3.802,=0.005). BSP showed that the DNA methylation rate of ZNF772 promoter region (-420,-422 locus) in SCC group was significantly higher than that in control group (=8.566,=0.038;=6.332,=0.043). Spearman correlation analysis showed that,in SCC group,DNA hypermethylation in ZNF772 promoter was negatively correlated with the mRNA expression (=-0.351,=0.045;=-0.349,=0.032) and was significantly correlated with HPV16/18 infection,tumor size,World Health Organization pathological grade,and International Federation of Gynecology and Obstetrics clinical stage (=0.018,=0.012,=0.009,and =0.035,respectively). The DNA hypermethylation in the promoter region of ZNF772 gene is involved in the occurrence and development of cervical cancer.
Cell Line, Tumor ; DNA Methylation ; DNA-Binding Proteins ; genetics ; Female ; Gene Expression Regulation, Neoplastic ; Human papillomavirus 16 ; Human papillomavirus 18 ; Humans ; Promoter Regions, Genetic ; Uterine Cervical Neoplasms ; genetics ; Zinc Fingers

OBJECTIVE: Human papillomaviruses (HPVs) are among the agents responsible for infection and cancer of the skin and mucous membranes in the human body. The aim of this study was to investigate the frequency and type distribution of HPVs in married female patients with gynecological complaints, who had visited the Maternity Hospital in Erzurum, Turkey. METHODS: In this study, 263 cervical swab samples were taken from married women using the Pap smear method and were investigated for positive reactivity against HPV. The L1 gene region of HPV was investigated using molecular methods. For this purpose, polymerase chain reaction (PCR) assays and sequence analysis of positive samples were performed. Phylogenetic analyses were performed using a bioinformatics approach after sequencing. RESULTS: HPV-DNA was detected in 17 (6.5%) samples. Highest positive reactivity to HPV-DNA was found in the 35–44 age group at 9.2%. Fourteen out of seventeen positive samples were included in the phylogenetic analysis. All isolates clustered in the Alphapapillomavirus genus. Six samples were found to be HPV 70 positive, four were HPV 16 positive, and the rest were HPV 54, 72, 81, and 114 positive. When genotyping data were evaluated according to the risk group, we found that 28.6% of the 14 samples were found to be high risk-HPV, and 71.4% were low risk-HPV. CONCLUSIONS: As per our knowledge, this is the first report on the phylogenetic analysis of HPV genotypes isolated from women in Turkey. The prevalence of low- and-high risk HPV was determined in married women in Erzurum, and these results contribute to the epidemiological data on the distribution of HPV types for this region.
Alphapapillomavirus ; Computational Biology ; Female ; Genotype ; Hospitals, Maternity ; Human Body ; Human papillomavirus 16 ; Humans ; Methods ; Mucous Membrane ; Papanicolaou Test ; Papillomavirus Infections ; Polymerase Chain Reaction ; Prevalence ; Sequence Analysis ; Skin Neoplasms ; Turkey ; Vaginal Smears

OBJECTIVE: To evaluate the risk of genotype-specific human papillomavirus (HPV) infections for the spectrum of cervical carcinogenesis and the distribution of HPV types according to age and different cervical lesions METHODS: This study included HPV-positive women who underwent cervical biopsy at the Cheil General Hospital & Women's Healthcare Center between July 1, 2011 and December 31, 2017. HPV genotyping was conducted using a Cheil HPV DNA chip kit. RESULTS: The study sample consisted of 400 normal, 399 cervical intraepithelial neoplasia (CIN) 1, 400 CIN 2, 400 CIN 3, and 389 cervical cancer cases. HPV 16 was the most common type found with a prevalence of 9.5% in normal, 6.8% in CIN 1, 15.0% in CIN 2, 44.5% in CIN 3, and 64.3% in cervical cancer. The most common HPV types were 16, 52, 58, 53, 51, 56, 68, and 18 in all study samples. HPV 16, 31, 33, and 58 were more common in CIN 2/3 and cancer, and HPV 39, 51, 53, 56, 66, and 68 were more common in CIN 1 and normal cases (p<0.001). In CIN 3 and cervical cancer, HPV 16 was the most common type in all age groups. HPV 52 was the most common type in CIN 2 (all age groups) and in CIN 1/normal (age ≤30 years) cases. Among the high-risk HPV types, 16, 31, 33, 52, and 58 showed significant risk for high-grade disease. CONCLUSIONS: HPV 16, 31, 33, 52, and 58 showed the significant risk of high-grade disease for cervical carcinogenesis.
Biopsy ; Carcinogenesis ; Cervical Intraepithelial Neoplasia ; Delivery of Health Care ; Female ; Genotype ; Hospitals, General ; Human papillomavirus 16 ; Humans ; Oligonucleotide Array Sequence Analysis ; Papillomaviridae ; Prevalence ; Uterine Cervical Neoplasms

No abstract available.
Human papillomavirus 16 ; Vaccination

Objective: To determine the prevalence of HPV high risk positivity among women patients ages 30 to 65 with biopsyproven external genital warts (condyloma acuminata) specifically for HPV 16, HPV 18, and for other high risk types 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66/68, 73, and 82. Methodology: A cross-sectional study was conducted at the Department of Obstetrics and Gynecology Out-Patient Services of the Philippine General Hospital involving 57 women, 30 to 65 years old, with biopsy proven external genital warts or condyloma acuminata. These women underwent human papillomavirus (HPV) genotyping test for the high risk types (HR-HPV) from cervical samples using the automated polymerase chain reaction (PCR) technology. Results: Fifteen out the 57 subjects had at least one of the HR-HPV types for an overall prevalence of 26.3%. Of the 15, 8 (53.3%) had at least 2 HR-HPV types with one subject having the most number of types at 6. Among the strains, the most common is HPV 51 and 52 each with a prevalence of 8.77% followed by HPV 53 and 59 at 7% each. HPV 16 and 18 each only had a 3.5% prevalence the same as HPV 58, 73, and 82. HR-HPV positivity was most common in the 30 to 39 age group (80%), and equally in the nulligravid and the secundigravid (40% each). None had current or past cigarettesmoking history and 33% had some form of hormonal contraception. Conclusion The overall prevalence of high risk HPV (HR-HPV) among these 57 Filipino women with external genital warts is 26.3%. The higher prevalence of HPV 51, 52, 53, and 59 over HPV 16 and 18 in this group does not follow the usual epidemiological characteristics reported about this disease.
Outpatients ; Human papillomavirus 16 ; Philippines ; Papillomaviridae