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

BACKGROUND: Variant analysis of distinct HPV types is important from different aspects including epidemiology, pathogenicity, and evolution. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Clinical validation of the Roche cobas HPV test on the Roche cobas 5800 system for the purpose of cervical screening.

This study assessed the relative clinical sensitivity and specificity, as well as reproducibility, for high-risk HPV types of the Roche cobas HPV test when processed using the Roche cobas 5800 system. The results from this study demonstrate that the cobas HPV test using the cobas 5800 system fulfils the Meijer criteria for use in population-based cervical screening. This clinical validation study also examines the clinical sensitivity and specificity based on partial genotyping, with separate detection of HPV16 and HPV18, compared with the Roche cobas 4800 HPV test, a second-generation standard comparator assay. The cobas HPV test has a relative clinical sensitivity of 1.000, when compared with the cobas 4800 HPV test to detect histologically confirmed CIN2+ lesions in woman aged 30 years or older, with a relative clinical specificity of 0.995. The general intra- and inter-laboratory agreement for the cobas HPV test on the cobas 5800 system for finding a HPV positive result were 99.1% and 99.6%, respectively.IMPORTANCEThis study demonstrates, for the first time, the clinical performance of the Roche cobas HPV test when processed using the new cobas 5800 system [cobas (5800)]. This study shows that the cobas (5800) demonstrates relative clinical sensitivity and specificity, when compared with a standard comparator HPV test, which meets the international HPV test validation requirements. Intra- and inter-laboratory reproducibility also fulfills these criteria. The current study demonstrates that the cobas (5800) can be used for primary HPV-based cervical screening on cervical specimens.

Genetic diversity, variation and recombination among the human papillomaviruses (HPVs) genomes isolated in China: a comparative genomic and phylogenetic analysis.

Human papillomaviruses (HPVs) are widespread, sexually transmitted group of viruses that infect most individuals at some stage, causing genital warts and cancers. They are members of the Papillomaviridae family, which contains about 400 HPV types. China is among the high HPV burden countries with reported infections of multiple HPV types, accounting for 17.3% of global deaths and 18.2% of global new cases. Thus, understanding the genetic variation and geographic diversity characteristics of HPVs isolated in China is critical for global HPV prevention strategies. Thus, we analyzed the available HPV genome sequences isolated in China that grouped into two categories (alpha- and gamma-papillomaviruses) based on full-length genomes. The most common were HPV-16, -6, -58, and -52 respectively. In addition, four of the novel strains isolated in China, e.g. TG550, JDFY01, CH2, and L55 clustered with the HPV-mSK 159, 244, 201, and 200 respectively. Our phylogeographic network analysis indicated that the L55, TG550, and CH2 are genetically identical to the mSK 200, 046, and 201 respectively, while JDFY01 appeared separately, connected to the mSK-040 following five mutational steps. Also, we found ten recombination events among HPV-6/11 types within their E1, E2, E7, L1/L2 proteins, and Long Control Region ORFs. We achieved the consensus amino acid sequences of HPV proteins and found a conserved stretch of amino acids within E5A of all HPVs circulating in China. These findings offer valued insights into the genetic relationships, distribution, and evolution of the HPVs in China that may assist in adapting effective HPV preventive measures.

Criteria for second generation comparator tests in validation of novel HPV DNA tests for use in cervical cancer screening.

While HC2 and GP5+/6+ PCR-EIA were pivotal in test validation of new HPV assays, they represent the first generation of comparator tests based upon technologies that are not in widespread use anymore. In the current guideline, criteria for second-generation comparator tests are presented that include more detailed resolution of HPV genotypes. Second-generation comparator tests should preferentially target only the 12 genotypes classified as carcinogenic (IARC-group I), and show consistent non-inferior sensitivity for CIN2+ and CIN3+ and specificity for ≤CIN1 compared to one of the first-generations comparators, in at least three validation studies using benchmarks of 0.95 for relative sensitivity and 0.98 for relative specificity. Validation should take into account used storage media and other sample handling procedures. Meta-analyses were conducted to identify the assays that fulfill these stringent criteria. Four tests fulfilled the new criteria: (1) RealTime High-Risk HPV Test (Abbott), (2) Cobas-4800 HPV test (Roche Molecular System), (3) Onclarity HPV Assay (BD Diagnostics), and (4) Anyplex II HPV HR Detection (Seegene), each evaluated in three to six studies. Whereas the four assays target 14 carcinogenic genotypes, the first two identify separately HPV16 and 18, the third assay identifies five types separately and the fourth identifies all the types separately.

Unveiling the seroprevalence of human papillomavirus in Guangdong, China: Implications for vaccination strategies.

Seroepidemiological characteristics of human papillomavirus (HPV) in community residents reflect natural infection and can guide the reform of vaccination programs. A population-based serological survey was conducted in Guangdong Province. Serum anti-HPV IgG antibody levels were determined by an ELISA. Neutralizing antibodies against HPV6, 11, 16, and 18 were detected via a pseudovirus-based neutralization assay (PBNA). A total of 5122 serum samples were collected from community residents, including 1989 males and 3133 females, in three cities of Guangdong Province. The rate of HPV IgG antibody positivity in females was 5.39% (95% CI: 4.6-6.2), which was greater than that in males (2.36%; 95% CI: 1.7-3.1). HPV IgG antibodies were more frequently detected in females aged 51-60 years (11.30%; 95% CI: 7.6-16.0), whereas in males, the detection increased with age and reached 4.94% (95% CI: 2.8-6.9) in the group aged ≥71 years. The seropositivity of neutralizing antibodies against HPV6 and 11 was greater than that against HPV16 and 18. The serum neutralizing antibody titers in individuals who received three doses of a vaccine were 7- to 12-fold greater than those in individuals who did not receive the vaccine. The neutralizing antibody titers slightly decreased within 40 months and ranged from 0.038 to 0.057 log ED50 per month. A moderate consistency between the HPV ELISA and PBNA results was observed (Kappa score = 0.49, r = 0.249, 0.635, 0.382, and 0.466 for HPV6, 11, 16, and 18, respectively). The HPV seropositivity rate among healthy residents of Guangdong Province was found to be low among children and adolescents and to increase with age. The serum neutralizing antibody titers were significantly greater in the vaccine group than that in the control group, and this difference persisted over time, which indicated promising protection against HPV infection.

High prevalence of HPV-56 and HPV-39 in Sari, Iran: an analysis of genotype distribution.

BACKGROUND: Human papillomavirus (HPV) is responsible for the most common sexually transmitted infection, particularly among sexually active individuals. Understanding the geographical distribution and epidemiology of the most prevalent HPV genotypes is essential for developing effective prevention strategies. Consequently, this study aimed to examine the distribution of HPV genotypes among HPV-positive women and men in Sari, the capital city of Mazandaran province in northern Iran. MATERIALS AND METHODS: HPV DNA was extracted (PZP Company, Molecular IVD, Iran) from genital and cervical samples of the study participants. Genotyping was conducted for 90 cases utilizing the High + Low Papilloma Strip test (Operon Company, Spain). Demographic data were statistically analyzed in correlation with the virological data (STATA version 17). RESULTS: Overall, 67.7% (61 out of 90) of the cases tested positive for HPV, with 75% of those being classified as high-risk. The participant group consisted of 92% females (83) and 8% males (7). The highest HPV prevalence, 75% (36), was observed in females and males aged under 31, with the majority of positive cases belonging to high-risk genotypes. The most frequently identified genotypes were HPV-11 (23%), HPV-6 (21%), HPV-56 (18%), HPV-39 (16%), HPV-16, HPV-91, and HPV-66 each comprising (14%). HPV-56 was the most common high-risk genotype, accounting for 11 cases (18%), followed by HPV-39, which was present in 10 cases (16%). CONCLUSION: The prevalence of HPV infection was particularly high among individuals under the age of 31 for both genders, with men exhibiting a 100% infection rate. These findings emphasize the urgent need for targeted education aimed at the younger population and the implementation of infection control measures. Specifically, widespread HPV vaccination targeting HPV-6, HPV-11, HPV-39, and HPV-56 should be prioritized for the general population.

Population-based age- and type-specific prevalence of human papillomavirus among non-vaccinated women aged 30 years and above in Germany.

BACKGROUND: A persisting high-risk human papillomavirus (HR-HPV) infection is causal for cervical cancer; however, there is limited population-based data on the prevalence of HPV infections in Germany. We assessed the age and type-specific HPV prevalence, and associated risk factors in HPV unvaccinated women aged 30 and above. METHODS: The MARZY prospective population-based cohort study was conducted between 2005 and 2012 in Mainz and Mainz-Bingen, Germany. Eligible women were randomly recruited from population registries and invited for cervical cancer screening (n = 5,275). A study swab (liquid-based cytology) was taken and HPV testing was performed with GP5+/6 + polymerase chain reaction (PCR) followed by genotyping. We assessed HPV types as HR-HPV, 'moderate' risk and low-risk (LR-HPV). Logistic regression was performed to identify factors associated with HPV infection, stratified by HPV types. RESULTS: 2,520 women were screened with a valid PCR result. Overall HPV prevalence was 10.6% (n = 266), with 6.5% HR-HPV positive (n = 165), 1.5% 'moderate' risk type (n = 38) and 3.3% LR-HPV type (n = 84) positive. 8.9% had a single infection (n = 225) and 1.6% had multiple types (n = 41). The most common HR-HPV types were 16, 56, 52 and 31 and LR-HPV 90 and 42. Of 187 HR-HPV infections detected (among 165 women), 55.1% (n = 103) were with HPV types not covered by available bivalent or quadrivalent HPV vaccines. About 23% (n = 43) were of types not covered by the nonavalent vaccine (HPV 35, 39, 51, 56, 59). The HR and LR-HPV prevalence were highest in the age group 30-34 years (HR 9.8%, 'moderate' risk 3.0% and LR 5.6%), decreasing with increasing age. HR-HPV prevalence in women with normal cytology was 5.5%. In women with a high-grade squamous intraepithelial lesion (HSIL), prevalence was 66.7%. Women currently not living with a partner and current smokers had increased chances of an HR-HPV infection. CONCLUSION: The overall population-based HPV prevalence was relatively high. An important share of prevalent HR-HPV infections constituted types not covered by current HPV vaccines. With the advent of HPV screening and younger vaccinated cohorts joining screening, HPV types should be monitored closely, also in older women who were not eligible for HPV vaccination.

Characterization of multiple human papillomavirus types in the human vagina following ovarian hormonal stimulation.

The objective of study was to characterize HPV in vaginal samples from women being seen at the Center for Reproductive Medicine and Infertility at Weill Cornell Medicine before and following ovarian stimulation. A total of 29 women made samples available for analysis by viral metagenomics. Eighteen women were HPV-positive, six (33.3%) at their initial visit and 15 (83.3%) following hormone stimulation (p = 0.0059). Pairwise comparison of nucleotide sequences and phylogenetic analysis showed the classification sequences into two genera: Alphapapillomavirus and Gammapapillomavirus. Sequences were from 8 HPV types: HPV 51 (n = 2), HPV 68 (n = 1), HPV 83 (n = 9), HPV 84 (n = 2), HPV 121 (n = 6), HPV 175 (n = 1) and HPV 190 (n = 1). Additionally, C16b and C30 likely represent new types. In summary, multiple HPV types are present in the vagina of reproductive age women and are induced by hormone used to stimulate ovulation.

Distribution and diagnostic value of single and multiple high-risk HPV infections in detection of cervical intraepithelial neoplasia: A retrospective multicenter study in China.

The risk associated with single and multiple human papillomavirus (HPV) infections in cervical intraepithelial neoplasia (CIN) remains uncertain. This study aims to explore the distribution and diagnostic significance of the number of high-risk HPV (hr-HPV) infections in detecting CIN, addressing a crucial gap in our understanding. This comprehensive multicenter, retrospective study meticulously analyzed the distribution of single and multiple hr-HPV, the risk of CIN2+, the relationship with CIN, and the impact on the diagnostic performance of colposcopy using demographic information, clinical histories, and tissue samples. The composition of a single infection was predominantly HPV16, 52, 58, 18, and 51, while HPV16 and 33 were identified as the primary causes of CIN2+. The primary instances of dual infection were mainly observed in combinations such as HPV16/18, HPV16/52, and HPV16/58, while HPV16/33 was identified as the primary cause of CIN2+. The incidence of hr-HPV infections shows a dose-response relationship with the risk of CIN (p for trend <0.001). Compared to single hr-HPV, multiple hr-HPV infections were associated with increased risks of CIN1 (1.44, 95% confidence interval [CI]: 1.20-1.72), CIN2 (1.70, 95% CI: 1.38-2.09), and CIN3 (1.08, 95% CI: 0.86-1.37). The colposcopy-based specificity of single hr-HPV (93.4, 95% CI: 92.4-94.4) and multiple hr-HPV (92.9, 95% CI: 90.8-94.6) was significantly lower than negative (97.9, 95% CI: 97.0-98.5) in detecting high-grade squamous intraepithelial lesion or worse (HSIL+). However, the sensitivity of single hr-HPV (73.5, 95% CI: 70.8-76.0) and multiple hr-HPV (71.8, 95% CI: 67.0-76.2) was higher than negative (62.0, 95% CI: 51.0-71.9) in detecting HSIL+. We found that multiple hr-HPV infections increase the risk of developing CIN lesions compared to a single infection. Colposcopy for HSIL+ detection showed high sensitivity and low specificity for hr-HPV infection. Apart from HPV16, this study also found that HPV33 is a major pathogenic genotype.

Update on Effects of the Prophylactic HPV Vaccines on HPV Type Prevalence and Cervical Pathology.

Most national prophylactic HPV vaccination programs started in approximately 2008, with either the bivalent Cervarix HPV16/18 or quadrivalent Gardasil (HPV6/11/16/18) vaccines, which were then followed by introduction of the nonavalent Gardasil 9 (HPV6/11/16/18/ 31/33/45/52/58) vaccine from 2015. Since that time, these products have demonstrated their ability to prevent infection with vaccine-covered HPV types and subsequent development of HPV-related cervical and genital pathologies. The data indicate that vaccination of young girls prior to sexual debut is more effective than vaccination of older HPV+ve women. Although some studies have shown a decline in the prevalence of vaccine-covered HPV types, there are national and regional differences in overall vaccine efficacy. Furthermore, several recently published studies show an increase in the prevalence of non-vaccine-covered HPV types in vaccinated populations, which is indicative of HPV type-replacement. It is also notable that vaccine-related changes in HPV type prevalence spread between vaccinated and unvaccinated women at the same geographical location-presumably via sexual transmission. In conclusion, it is not yet clear what effect dissemination of vaccine-associated changes in HPV type prevalence will have on vaccine efficacy and cervical pathology, particularly in mixed populations of vaccinated and unvaccinated women. However, it is very clear these observations do underscore the need for long-term continuation of cervical screening combined with regular reassessment of testing practices.