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

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.

Interaction of High- and Low-Risk human papillomavirus genotypes is associated with a reduced risk of developing cervical cancer (Preprint)

BACKGROUND Cervical cancer is among the most common type of cancers in women and is associated with human papillomavirus (HPV) infection. OBJECTIVE The link between cervical cancer and high-risk HPV infection has been well documented, although the effect of simultaneous infection with high- and low-risk HPV or low-risk HPV alone on the risk of developing cervical malignancy is remained to be unanswered in guideline METHODS We have investigated the association of high and low-risk HPVs (HR or LR) genotype with cervical carcinoma risk, as well as pathological and cytological information in cases recruited from a population-based cohort study of 790 patients. RESULTS The percentage of HR+LR and HR-HPV16/18 were 9.30% and 11.20% in class II, 7.15% and 7.10% in class IV and 7.15% and 5.80% in As-CUS smears. Interestingly concurrent infection with HR-HPV and LR-HPV types led to a notable decline in the risk of developing malignancy in comparison with the high-risk group (OR=0.3 (0.098-0.925), p-value=0.04). The percentage of individuals with cervical malignancy was 10.2% and 28.2% within the co-infected and the HR-HPV participants. CONCLUSIONS Our finding demonstrated that simultaneous infection with high- and low-risk HPV reduces the risk of cervical malignancy.

HPVE6-USP46 Mediated Cdt2 Stabilization Reduces Set8 Mediated H4K20-Methylation to Induce Gene Expression Changes

E6 from high-risk strains of HPV is well known to transform cells by deregulating p53. We reported that in HPV transformed cell-lines E6 from high-risk HPV can recruit the USP46 deubiquitinase to substrates such as Cdt2 and stabilize the latter, and that USP46 is important for growth of HPV induced tumors in xenografts. Here we show that in cervical cancer biopsies the stabilization of Cdt2 in the HPV-induced cancers leads to the decrease of a CRL4-Cdt2 substrate, the histone H4K20 mono-methyltransferase Set8, and decrease in H4K20me1 or H4K20me3 that can be detected by immunohistochemistry. In HPV-transformed cancer cell lines in vitro, knockdown of E6 decreases Cdt2 and increases Set8. Co-knockdown of Set8 shows that some of the gene expression changes produced by E6 knockdown is due to the increase of Set8. EGFR and EGFR regulated genes were identified in this set of genes. Turning to the mechanism by which E6 stabilizes Cdt2, we find that a purified E6:USP46 complex has significantly more de-ubiquitinase activity in vitro than USP46 alone, demonstrating that E6 can directly interact with USP46 in the absence of other proteins and that it can substitute for the known activators of USP46, UAF1 and WDR20. Deletion mapping of Cdt2 shows that there are three discrete, but redundant, parts of the substrate that are essential for stabilization by E6: USP46. The helix–loop–helix region or the WD40 repeat driven beta-propeller structure of Cdt2 are dispensable for the stabilization implying that interaction with DDB1 (and the rest of the CRL4 complex) or with the substrate of the CRL4-Cdt2 E3 ligase is not necessary for E6:USP46 to interact with and stabilize Cdt2. The identification of 50 amino acid stretches in the 731 amino acid Cdt2 protein as being important for the stabilization by E6 underlines the specificity of the process. In summary, E6 activates the deubiquitinase activity of USP46, stabilizes Cdt2 utilizing multiple sites on Cdt2, and leads to degradation of Set8 and changes in gene-expression in HPV-transformed cells.

HPV-mediated Cervical Cancer: A Systematic review on Immunological Basis, Molecular Biology and Immune evasion mechanisms

Background: Human papillomavirus (HPV), one of the most frequently transmitted viruses globally, causing several malignancies including cervical cancer Aim: Owing to their unique pathogenicity HPV viruses can persist in the host organism for a longer duration than other virus types, to complete their lifecycle. During its association with the host, HPV causes various pathological conditions affecting the immune system by evading the host immune- mechanisms leading to the progression of various diseases, including cance Method: To date, ~ 150 serotypes were identified, and certain high-risk HPV types are known to be associated with genital warts and cervical cancer. As of now, two prophylactic vaccines are in use for the treatment of HPV infection, however, no effective antiviral drug is available for HPV-associated disease/infections. Numerous clinical and laboratory studies are being investigated to formulate an effective and specific vaccine again HPV infections and associated diseases Result: As the immunological basis of HPV infection and associated disease progress persist indistinctly, deeper insights on immune evasion mechanism and molecular biology of disease would aid in developing an effective vaccine. Conclusion: Thus this review focuses, aiming a systematic review on the immunological aspects of HPV-associated cervical cancer by uncovering immune evasion strategies adapted by HPV.

Detection and Outcome of Endocervical Atypia in Cytology in Primary HPV Screening Programme

Most endocervical adenocarcinomas (EAC) are associated with high-risk HPV (hrHPV) infection, with HPV genotypes 16, 18 and 45 accounting for >90% of the cases. Among endocervical glandular lesions, screening with hrHPV test has previously shown to predict the outcome better than cytology, although around one-fifth of the EAC remain negative both in hrHPV testing and cytology. The study consists of two consecutive HPV-primary screening rounds, conducted in 2012–2015 and 2017–2020. Of the 87 women aged 35 to 60 years of age diagnosed with Atypical endocervical cells, NOS or Atypical endocervical cells, favor neoplastic cytology during the first screening round, 63 (72.4%) were hrHPV positive and 24 (27.6%) were hrHPV negative. Among hrHPV positive patients, three EAC, two adenocarcinomas in situ (AIS), one AIS + high-grade intraepithelial lesion (HSIL) and 13 HSIL were found. Of the histologically verified lesions, 68.4% (13/19) were purely of squamous origin. All the EAC and AIS were HPV16 or HPV 18 positive. No high-grade histological lesions were found among the hrHPV negative patients with cytological glandular atypia. A later database search revealed one HPV-negative, gastric-type mucinous EAC that was missed by the HPV primary screening.