Common HPV Types Research Articles

Mucosal and cutaneous Human Papillomavirus seroprevalence among adults in the prevaccine era in Germany — Results from a nationwide population-based survey

BackgroundHuman Papillomavirus (HPV) vaccination of girls was introduced in Germany in 2007. However, data on the distribution of vaccine-relevant HPV types in the general population in Germany in the prevaccine era are limited. MethodsSerum samples collected during the German National Health Interview and Examination Survey 1998 (GNHIES98), a nationally representative study including men and women aged 18–79 years, were tested for antibodies to 19 mucosal and cutaneous HPV types. Multivariable regression models were developed to identify associations between demographic and behavioral characteristics and HPV seropositivity. ResultsOf the 6517 serum samples tested, almost a quarter was seropositive for at least one of the nine HPV vaccine types with no clear age-pattern. HPV-6 and HPV-59 were the most common mucosal types, while HPV-1 and HPV-4 were the most common cutaneous HPV types. Factors independently associated with HPV-16 seroprevalence were seropositive to other sexually transmitted infections and lifetime number of sex partners, as well as urbanity (only among females). ConclusionsPrevalence of naturally acquired antibodies to HPV types which can be prevented by vaccination is high in both sexes and all age groups. These data can serve as baseline estimates to evaluate the population-level impact of the current vaccination strategy.

Human Papillomavirus Status in Primary Lesions and Pelvic Lymph Nodes and Its Prognostic Value in Cervical Cancer Patients with Lymph Node Metastases.

BackgroundThe aim of this study was to assess the presence of HPV DNA in cervical tissues and lymph nodes in patients who have uterine cervical neoplasms with lymphatic metastases and who underwent surgery for invasive cervical cancer and pelvic lymphadenectomy, to establish the utility of HPV type and viral load in predicting disease progression.Material/MethodsWe retrospectively assessed 88 patients with uterine cervical neoplasms with lymph node metastases. All 88 patients were in FIGO stage IA-IIB. A total of 316 paraffin-embedded archival tissues (88 cervical samples and 228 pelvic lymph node specimens) were acquired. All the samples were analyzed using real-time PCR to determine HPV DNA presence/type and to quantify viral load.ResultsIn total, 17 HPV genotypes were detected in the cervical lesions and pelvic lymph nodes of the patients. The most common HPV type in all samples was HPV16, followed by HPV18. The existence of HPV16 DNA and low HPV16 viral load in cervical lesions were also significantly associated with disease recurrence. Furthermore, lymphovascular space involvement was also correlated with worse disease outcome.ConclusionsHPV16 DNA presence and low viral load in primary lesions can be used to predict disease recurrence. HPV DNA is a favorable prognostic indicator in patients with uterine cervical neoplasms who have lymphatic metastases.

Incident genital HPV infections and potential impact of HPV vaccines in adult women living with HIV/AIDS

ABSTRACT This study aims to describe and characterize incident HR-HPV infections and associated diseases in HIV-infected women. 805 HIV-infected women enrolled in the VALHIDATE Study were screened and followed-up for HPV by co-testing. Social, behavioral and health data were collected. HPV-DNA positive samples were typed using a commercial kit or RFLP analysis. Conventional Pap-smears were evaluated using the 2001 Bethesda System. The participants with abnormal cytological results were referred for colposcopy. 565 HIV-infected women (median age: 43 years) were analysed, 40.9% had >5 lifetime sexual partners, 77.2% contracted HIV through sexual intercourse, 93% were receiving antiretroviral treatment and 77.3% had undetectable HIV-RNA. The women underwent 1254 follow-ups (median follow-up: 33 months) for 1430.6 PersonYear-Follow-Up. 37.4% of baseline HPV-negative women acquired incident HPV-infections, 69.6% of which were HR-HPVs. HPV-53 was the most common HPV type detected (9.3%). 18.2% of women showed incident or progressive cytological abnormalities (7.8% ASC-US, 9.7% LSIL and 0.6% HSIL) and colposcopy revealed CIN2 (N = 2), CIN1 (N = 2) and VIN3 (N = 1). The preventable fraction of incident infections was 11.3%, 16.7%, and 35.2% for the 2v-4v-9v-HPV vaccines respectively (χ2 p < 0.0001). The overall burden of incident lesions attributable to the vaccine types were 9.1% for 2v-, 14.5% for 4v- and 30.9% for 9v-vaccine. High HPV incidence rates and high percentages of multiple HR-HPV infections were observed in a cohort of HIV-infected women receiving effective antiretroviral treatment. Primary prevention strategies based on the new 9v-HPV vaccine may help to prevent incident infections and disease progression in this cohort of women.

Abstract 3326: Upregulation of epigenetic changes acquired by HPV16 E6/E7 oncoproteins in mouse keratinocytes: Targeting ATM/PI3K

Abstract Human Papillomavirus (HPV), a non-enveloped epitheliotropic double stranded DNA virus, is an etiological agent of oral cancer. Oral cancer is related to the persistent infection by high-risk HPV type 16, E6/E7 oncoproteins. The E6/E7 oncoproteins significantly contribute to the carcinogenic genetic instability effect of high-risk HPV through the degradation of two gatekeeper proteins, p53 and pRB, respectively. The ATM gene, also known as a gatekeeper protein plays a central role in the complex processes that repair DNA strand breaks. The ATM gene is located at 11q22.3 and belongs to a protein family known as the PI3K. Many studies have tried to clarify the epigenetic instability role of ATM in cancer function and susceptibility. However, there are no studies addressing the relationship between HPV infection-oral cancer, ATM/PI3K expression, and genomic instability. The aim of this study is to analyze the influence of HPV16 E6/E7 oncoproteins in oral cancer and the epigenetic profile. In our experimental procedures, we proposed a novel approach to study HPV-induced epigenetic changes with reconstructed human oral epithelium in SCID mouse. We used HPV-16, which is the most common HPV type found in oral cancer. Two plasmids were used to produce HPV-16 E6/E7. The first plasmid p16sheLL expresses the two viral capsid proteins, L1 and L2. The second plasmid pBR322HPV16 contains the full length HPV-16 genome. This approach closely mimics the architecture of normal human oral epithelium. In our study, we first focused on analyzing selected cellular gene loci where DNA methylation profiles are known to be altered, either by HPV infection or in oral cancer. We examined the following gene promoters DcR1/DcR2 (apoptosis regulation), p16 (cell cycle control), DAPK (cancer metastasis), and MGMT (DNA repair). We also analyzed progressive morphological and cytopathic changes in the HPV-infected oral epithelia. These data indicate that HPV E6/E7 oncoproteins can promote increased upregulation of apoptosis, disrupt cell cycle regulation, and decrease DNA double strand break repair. Epigenetics and chromosomal instability events were noted, specifically, the deletion of the distal region of chromosome 11q22-23 in the E6/E7 transfected keratinocytes. These results indicate that HPV-16, E6/E7 oncoproteins induced epigenetic changes in mouse keratinocytes, which may further promote oral carcinogenesis. Citation Format: Eva McGhee, Mengtao Li, Yi-Ling Lin, Liliana Zarate, Naomi Long, Mai Do, Chinelo Ezechukwu, Nichelle Cox, Hyun Chung, Jenna Cormier, Meidrah Tyler, Victoria Vidal, Billy Ballard, Roland Pattillo, Jay Vadgama. Upregulation of epigenetic changes acquired by HPV16 E6/E7 oncoproteins in mouse keratinocytes: Targeting ATM/PI3K [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3326.

PHS94 - Differences in HPV Vaccine Uptake by Nativity Status Among American Men Aged 18-32

About 16,500 HPV-associated cancers occur in the United States annually among men. HPV is thought to be responsible for more than 90% of anal, 70% of oropharynx and 60% of penile cancers. HPV vaccination reduces the risk of infection from the most common HPV types that cause HPV-associated cancers. There is limited research on vaccination uptake among men based on nativity status (i.e., U.S.- versus foreign-born). We examined whether there were significant differences in HPV vaccination uptake between U.S.-born and foreign-born men. The National Health Interview Survey 2014-2016 was examined for men, aged 18–32 years (n =6598). HPV vaccine initiation was defined as receipt of at least one dose of the vaccine and completion as receipt of the three doses. Weighted, multivariable binary logistic regression models were used to assess the association between nativity status and HPV vaccine uptake, adjusting for demographic, socioeconomic, and healthcare factors. Approximately 16% of men self-identified as foreign-born, 8% had initiated the HPV vaccine, and 3% had completed the HPV vaccine. After adjusting for covariates, compared to U.S.-born men, foreign-born men were 47% [(adjusted odds ratio) 0.53; (95 % confidence interval) 0.36–0.78] less likely to initiate the HPV vaccine but there were no difference between the two groups in terms of vaccine completion. Men were more likely to initiate and complete the HPV vaccine if they had visit the doctor’s office 6+ times (3.13; 2.16–4.53), and 1-5 times (1.84; 1.42–2.39) vs. no doctor’s office within the last 12 months. The results held for HPV vaccine completion. We found that HPV vaccine uptake among men was very low overall, and foreign-born men had lower initiation compared to US born men. Public health interventions to improve HPV vaccination need to be developed for all men irrespective of nativity status.

Comparison of the Cepheid Xpert HPV test and the HC2 High-Risk HPV DNA Test for detection of high-risk HPV infection in cervical smear samples in SurePath preservative fluid.

PurposeCytological and histological cervical screening methods for human papillomavirus may be subjective. Current guidelines recommend the use of direct human papillomavirus screening by molecular methods in conjunction with cytology for the detection of high-risk human papillomavirus types with carcinogenic potential. In this study, we compared the performance of the molecular Cepheid Xpert HPV test to the FDA-approved HC2 High-Risk HPV DNA Test on samples from patients presenting for cervical screening, regardless of the cytology results, in which cervical cell samples were originally collected for Papanicolaou (Pap) smear specimens in Becton Dickinson (BD) SurePath preservative fluid.MethodologyCervical cells were obtained for Pap smear specimens from 343 women attending Qatif Central Hospital in Saudi Arabia for cervical cancer screening using a Cytobrush Plus GT and immersed in BD SurePath preservative fluid in BD SurePath collection vials. The study was carried out between December 2015 and July 2016.ResultsThe Xpert HPV test was positive in 27 (7.9 %) of the samples. The HC2 High-Risk HPV DNA Test was positive in 32 (9.3 %) of the samples. The most common HPV types according to the Xpert HPV test were HPV other types, either alone (n=15) or in combination with HPV16 (n=3). The overall concordance rate between the tests was 98.5 %. The positive concordance was 84.4 %.ConclusionThe Xpert HPV test is convenient to use on cervical cell samples collected for Pap smear specimens in BD SurePath preservative fluid within an hour and is a viable alternative to the HC2 High-Risk HPV DNA Test for HPV testing.

Prevalence and distribution of human papillomavirus genotypes in Chinese women between 1991 and 2016: A systematic review

BackgroundHuman papillomavirus (HPV) associated cervical cancer is one of the most common cancers and ranked as the eighth most common killer for Chinese women. A dozen of HPV vaccines are being developed in China without a solid China-specific distribution of carcinogenic HPV types, thus, we performed this systematic review to explore the China-specific spectrum of high-risk types causing cancer. MethodsStudies on HPV infection among Chinese women were searched. All retrieved articles were screened and reviewed by a standardized algorithm. Distribution of carcinogenic HPV types and age-specific prevalence were analyzed using random-effects model. ResultsA total of 303 articles were included in the final analysis. The top 10 common HPV types detected in ICC patients, in descending order of frequency, were HPV 16 (62.5%), 18 (12.4%), 58 (8.6%), 52 (5.7%), 33 (4.6%), 31 (3.5%), 55 (2.4%), 68 (2.4%), 53 (2.2%) and 45 (2.0%) respectively. Similar spectrum was found in women with precancer. The prevalence of HPV infection peaked between 20 and 24 years with a rate of 24.3%, thereafter declined substantially and stabilized at middle-ages. Compared to women living in the developed provinces, the second peak was observed among women aged 45–55 years in less developed regions. ConclusionIn general, the spectrum of HPV types in women with precancer/cancer and the pattern of age-specific prevalence were consistent with that of elsewhere worldwide. However, some distinguished characteristics could also be concluded, and these imprinting should be considered and integrated when developing vaccines and strategy for disease control in China.

Papillomaviruses: HPV as the etiological factor of head and neck cancers

Abstract The HPV virus, belonging to papillomaviruses, causes genital, lung, head and neck cancers. It is currently estimated that there are 190 types of HPV. Over 700 million people worldwide are infected with the virus. In the United States, 14 million new infections occur every year. The most common HPV types responsible for carcinogenesis of head and neck areas are types 16 and 18. The virus infects human epithelial cells, for example during a sexual intercourse. Transmission from mother to child during birth is also possible. There is evidence linking HPV with laryngeal cancer, leukoplakia, tonsil cancer or Bowen’s disease. HPV vaccines are available to help prevent infection by certain types of the virus, e.g. 9-valent HPV vaccine called Gardasil-9. 1. Introduction. 2. Structure of HPV. 3. Taxonomy. 4. Infection. 5. Pathogenicity. 6. Treatment. 7. Vaccines. 8. Summary

Human papillomavirus genotype distribution in cervical samples among vaccine naïve Barbados women.

This study was undertaken to provide baseline HPV genotype distribution among women in Barbados before HPV immunization was introduced. This information would then be used as a denominator for post-vaccine surveillance and is expected to aid in understanding the effect of vaccination on cervical disease in Barbados. Liquid-based cytology specimens were collected from 413 women (age range 18-65years) attending three clinics, in a pre-vaccination, population-based study. After consent was obtained, sexual behavior and socio-demographic information were acquired from self-administered questionnaires. HPV types were detected using Luminex-based HPV PCR genotyping methodology. HPV was detected in 33% (135/413) of the subjects overall (95% CI 32.7, 33.37), of which 70% (95/135) were high-risk types, with 35 different types being detected in this population. Single and multiple high-risk HPV types were detected in 14% (13/95) and 31% (29/95) of the subjects, respectively. The most common high-risk HPV types detected were 45(n = 22, 23%), 16 (n = 17, 18%), 52 (n = 16, 17%), and 58 (n = 10, 11%). Persons with the highest level of infection by age were 21-25 (n = 25/135;19%; 95% CI 18.8, 19.3); 26-30 (n = 22/135;16%; 95% CI 15.9, 16.2); 31-35 (n = 19/135;14%; 95% CI 13.9, 14.2); 36-40 (n = 17/135;13%; 95% CI 12.2, 13.2), and 18-21 (n = 15/135;11%; 95% CI 10.9, 11.2). 91/413 (22%) persons had a normal cytology result. A high prevalence of HPV type 45 was found in the screening population of women in Barbados. The results of cytological examinations and HPV positivity suggest that both tests should be used for greater reliable diagnosis of HPV infection.

Expressions of programmed death (PD)-1 and PD-1 ligand (PD-L1) in cervical intraepithelial neoplasia and cervical squamous cell carcinomas are of prognostic value and associated with human papillomavirus status.

The programmed death 1/programmed death 1 ligand (PD-1/PD-L1) pathway can decrease the immune clearance effects of antigen-presenting cells and T lymphocytes to promote immune evasion of cervical cancer cells. However, the effects of this pathway on cervical intraepithelial neoplasia (CIN) progression and squamous cell carcinoma (SCC) metastasis are not clear. We herein investigated whether human papillomavirus infection could affect PD-1 and PD-L1 expression in CIN, and whether their expression is associated with CIN progression and SCC metastasis. We collected paraffin-embedded samples from two cohorts of patients: (i) CIN samples from cohort I (40 women who tested positive or negative for high-risk human papillomavirus [HR-HPV] with grades 0, I, and II-III CIN); and (ii) paired primary and metastatic tumor samples from cohort II (20 SCC patients with or without metastasis). Immunohistochemistry was used to detect expressions of PD-L1 in tumor cells and PD-1 in tumor-associated macrophages and tumor-infiltrating lymphocytes. We also measured P16INK4a expression and interferon-γ levels in the cervical tissues. The most common HPV type seen in both cohorts of patients was HPV16, followed by HPV18. Increase in PD-L1 and PD-1 expression was positively correlated with HPV-positivity, increase in CIN grade, and tumor metastasis. Furthermore, upregulation of the PD-1/PD-L1 pathway was associated with decreased expression of the pro-inflammatory cytokine, interferon-γ and increased expression of P16INK4a . Expression of PD-L1 and PD-1 could be used as clinical prognostic biomarkers for evaluating CIN and cervical cancer because of its positive correlation with CIN progression and tumor metastasis.

Cervical HPV type-specific pre-vaccination prevalence and age distribution in Croatia.

The main etiological factor of precancerous lesion and invasive cervical cancer are oncogenic human papillomaviruses types (HPVs). The objective of this study was to establish the distribution of the most common HPVs in different cervical lesions and cancer prior to the implementation of organized population-based cervical screening and HPV vaccination in Croatia. In this study, 4,432 cervical specimens, collected through a 16-year period, were tested for the presence of HPV-DNA by polymerase chain reaction (PCR) with three sets of broad-spectrum primers and type-specific primers for most common low-risk (LR) types (HPV-6, 11) and the most common high-risk (HR) types (HPV-16, 18, 31, 33, 45, 52, 58). Additional 35 archival formalin-fixed, paraffin embedded tissue of cervical cancer specimens were analyzed using LiPA25 assay. The highest age-specific HPV-prevalence was in the group 18–24 years, which decreased continuously with age (P<0.0001) regardless of the cytological diagnosis. The prevalence of HR-HPV types significantly increased (P<0.0001) with the severity of cervical lesions. HPV-16 was the most common type found with a prevalence (with or without another HPV-type) of 6.9% in normal cytology, 15.5% in atypical squamous cells of undetermined significance, 14.4% in low-grade squamous intraepithelial lesions, 33.3% in high-grade squamous intraepithelial lesions, and 60.9% in cervical cancer specimens (P<0.0001). This study provides comprehensive and extensive data on the distribution of the most common HPV types among Croatian women, which will enable to predict and to monitor the impact of HPV-vaccination and to design effective screening strategies in Croatia.

A population-based study of cervical cytology findings and human papillomavirus infection in a suburban area of Thailand

Despite the high incidence of cervical cancer in Thailand, large population-based studies on cervical cytology and HPV prevalence and genotype distribution are rare. This study aimed to determine cervical cytology results and the prevalence and distribution of HPV among Thai females in Bangkhayaeng subdistrict, Pathumthani province, Thailand. Of 4681 female inhabitants, aged 20–70years, 1523 women finally participated in the study. Cervical samples using liquid-based cytology were collected during February–August 2013 and analyzed for HPV genotype by the LINEAR ARRAY® HPV Genotyping Test (Roche, USA). All participants with abnormal cytology or HPV positivity underwent colposcopy and biopsy. Of 1523 eligible women, 4.1% had abnormal cytology including ASC-US (2.4%), LSIL (1.0%), and HSIL (0.5%). The HPV infection rate was 13.7%. The prevalences of high-risk, probable high-risk, and low-risk HPV types were 5.6%, 3.5%, and 6.8%, respectively. The most common high-risk HPV types detected were HPV-16 (1.31%), HPV-51 (1.25%), and HPV-52 (1.25%). The most common probable high-risk and low-risk HPV types detected were HPV-72 (1.51%), HPV-62 (1.38%), and HPV-70 (1.18%). The rates of CIN2–3 and cancer in this cohort were 1.4% and 0.3%, respectively. In conclusion, HPV prevalence in this study was lower than reported in studies conducted in Western countries or other Asia countries, despite the high prevalence of CIN2+ and cancer. HPV type screening results of the general population in Bangkhayaeng subdistrict were similar to those reported in other countries, with HPV-16 the most common type. However, higher frequencies of HPV-51 and HPV-52 were observed. Despite the availability of a free screening program in this area, the participation rate remains low.

HPV prevalence and type distribution in Cypriot women with cervical cytological abnormalities

BackgroundHuman papillomavirus (HPV) is the most common sexually transmitted agent, and it can cause cervical lesions and cancer in females. Currently, information regarding the prevalence of HPV in Cyprus is lacking. The aim of this study was to evaluate the HPV type-specific prevalence in 596 women, aged 19–65 years, with cytological abnormalities. Additionally, in a subset of 348 women for whom cytology results of the Pap test were available, the association between HPV infection and cervical disease was investigated.MethodsHPV detection and typing was carried out using PCR and restriction fragment length polymorphism analysis, respectively.ResultsOverall, the HPV prevalence was 72.8%, and it was shown to be age dependent, with a decreasing prevalence until the age of 45 years (p = 0.0018, χ2). Two hundred and fifty-eight women (59.4%) were infected with high-risk HPV, 151 (34.8%) with low-risk HPV, and 25 (5.8%) with HPV types of unknown risk. The most common high-risk HPV type was HPV16 (17.7%), followed by HPV31 (12.9%), HPV58 (7.1%), HPV68 (4.6%), HPV18 (4.1%), and HPV56 (3.7%). Among the women for whom cytology results were available, 268 (77%) were HPV positive, with a sample distribution as follows: 188 (74%) had atypical squamous cells of undetermined significance (ASCUS), 61 (85.9%) had low-grade squamous intraepithelial lesion (L-SIL), and 19 (82.6%) had high-grade squamous intraepithelial lesion (H-SIL). HPV16 was the most common type among women affected by L-SIL (19.7%) and H-SIL (15.8%), with HPV31 being the most common type in women affected by ASCUS (16.5%).ConclusionsThe present study provides the first epidemiological data related to HPV prevalence and type distribution in Cypriot women with cytological abnormalities.

Serine/Arginine-Rich Splicing Factor 3 and Heterogeneous Nuclear Ribonucleoprotein A1 Regulate Alternative RNA Splicing and Gene Expression of Human Papillomavirus 18 through Two Functionally Distinguishable cis Elements.

Human papillomavirus 18 (HPV18) is the second most common oncogenic HPV type associated with cervical, anogenital, and oropharyngeal cancers. Like other oncogenic HPVs, HPV18 encodes two major (one early and one late) polycistronic pre-mRNAs that are regulated by alternative RNA splicing to produce a repertoire of viral transcripts for the expression of individual viral genes. However, RNA cis-regulatory elements and trans-acting factors contributing to HPV18 alternative RNA splicing remain unknown. In this study, an exonic splicing enhancer (ESE) in the nucleotide (nt) 3520 to 3550 region in the HPV18 genome was identified and characterized for promotion of HPV18 929^3434 splicing and E1^E4 production through interaction with SRSF3, a host oncogenic splicing factor differentially expressed in epithelial cells and keratinocytes. Introduction of point mutations in the SRSF3-binding site or knockdown of SRSF3 expression in cells reduces 929^3434 splicing and E1^E4 production but activates other, minor 929^3465 and 929^3506 splicing. Knockdown of SRSF3 expression also enhances the expression of E2 and L1 mRNAs. An exonic splicing silencer (ESS) in the HPV18 nt 612 to 639 region was identified as being inhibitory to the 233^416 splicing of HPV18 E6E7 pre-mRNAs via binding to hnRNP A1, a well-characterized, abundantly and ubiquitously expressed RNA-binding protein. Introduction of point mutations into the hnRNP A1-binding site or knockdown of hnRNP A1 expression promoted 233^416 splicing and reduced E6 expression. These data provide the first evidence that the alternative RNA splicing of HPV18 pre-mRNAs is subject to regulation by viral RNA cis elements and host trans-acting splicing factors. Expression of HPV18 genes is regulated by alternative RNA splicing of viral polycistronic pre-mRNAs to produce a repertoire of viral early and late transcripts. RNA cis elements and trans-acting factors contributing to HPV18 alternative RNA splicing have been discovered in this study for the first time. The identified ESS at the E7 open reading frame (ORF) prevents HPV18 233^416 splicing in the E6 ORF through interaction with a host splicing factor, hnRNP A1, and regulates E6 and E7 expression of the early E6E7 polycistronic pre-mRNA. The identified ESE at the E1^E4 ORF promotes HPV18 929^3434 splicing of both viral early and late pre-mRNAs and E1^E4 production through interaction with SRSF3. This study provides important observations on how alternative RNA splicing of HPV18 pre-mRNAs is subject to regulation by viral RNA cis elements and host splicing factors and offers potential therapeutic targets to overcome HPV-related cancer.

Risk, Persistence and Multiplicity of HPV Infections among HIV Negative and HIV Positive Nigerian Women

Abstract 64 Background: The incidence, prevalence, persistence, and multiplicity of high-risk HPV infection is different between HIV positive and HIV negative women. We examined the association between HIV, prevalent HPV, and persistent HPV infections among women in a prospective cohort in Nigeria. Methods: We enrolled women presenting at cervical cancer screening programs in Abuja, Nigeria, between 2012 and 2014 and collected information on their demographic characteristics, risk factors of HPV infection, and cervical exfoliated cells samples at baseline, 6 month and 12 month follow-up visits. DNA enzyme immunoassay (DEIA) and Roche Linear Array HPV Genotyping Test were used to characterize HPV. Persistent HPV infection was defined as a positive result on 2 consecutive DEIA tests. We used logistic regression models to estimate the association between HIV and risk of HPV infection. Results: Among the 1,020 women enrolled, the mean age (±SD) was 37(8), and 44% and 56% were HIV+ and HIV-, respectively. HPV52 and 35 were the most common HPV types in the study population. The prevalence was 34% for any HPV, 24% for persistent HPV and 9% for multiple HPV infections; these were higher among HIV+ women (p-value &lt;0.001). The multivariate odds ratio (OR) and 95 % CI comparing HIV+ to HIV- women was 6.29 (95% CI 3.64 – 10.87, p-value &lt;0.001) for any high-risk HPV; 6.22 (95% CI 3.02 – 12.83, p-value &lt;0.001) for persistent high-risk HPV; and 6.46 (95% CI 2.69 – 15.52, p-value &lt;0.001) for multiple high-risk HPV infections, Conclusions: HIV infection is associated with increased risk of persistence and multiplicity of low-risk and high-risk HPV infections. These findings may explain, in part, the increased risk of cervical cancer among women with HIV infections. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: Sally N. Adebamowo No relationship to disclose Toyosi Olawande No relationship to disclose Ayotunde Famooto No relationship to disclose Eileen O. Dareng No relationship to disclose Olayinka Olaniyan No relationship to disclose Richard Offiong No relationship to disclose Clement A. Adebamowo Speakers' Bureau: Merck [Table: see text]

Durable immunity to oncogenic human papillomaviruses elicited by adjuvanted recombinant Adeno-associated virus-like particle immunogen displaying L2 17–36 epitopes

Vaccination with the minor capsid protein L2, notably the 17–36 neutralizing epitope, induces broadly protective antibodies, although the neutralizing titers attained in serum are substantially lower than for the licensed L1 VLP vaccines. Here we examine the impact of other less reactogenic adjuvants upon the induction of durable neutralizing serum antibody responses and protective immunity after vaccination with HPV16 and HPV31 L2 amino acids 17–36 inserted at positions 587 and 453 of VP3, respectively, for surface display on Adeno-Associated Virus 2-like particles [AAVLP (HPV16/31L2)]. Mice were vaccinated three times subcutaneously with AAVLP (HPV16/31L2) at two week intervals at several doses either alone or formulated with alum, alum and MPL, RIBI adjuvant or Cervarix. The use of adjuvant with AAVLP (HPV16/31L2) was necessary in mice for the induction of L2-specific neutralizing antibody and protection against vaginal challenge with HPV16. While use of alum was sufficient to elicit durable protection (>3 months after the final immunization), antibody titers were increased by addition of MPL and RIBI adjuvants. To determine the breadth of immunity, rabbits were immunized three times with AAVLP (HPV16/31L2) either alone, formulated with alum±MPL, or RIBI adjuvants, and after serum collection, the animals were concurrently challenged with HPV16/31/35/39/45/58/59 quasivirions or cottontail rabbit papillomavirus (CRPV) at 6 or 12 months post-immunization. Strong protection against all HPV types was observed at both 6 and 12 months post-immunization, including robust protection in rabbits receiving the vaccine without adjuvant. In summary, vaccination with AAVLP presenting HPV L2 17–36 epitopes at two sites on their surface induced cross-neutralizing serum antibody, immunity against HPV16 in the genital tract, and long-term protection against skin challenge with the 7 most common oncogenic HPV types when using a clinically relevant adjuvant.

The role of HPV genotyping testing in follow-up of high grade squamous intraepithelial lesion after treatment

To assess the clinical value of HPV genotyping in follow-up after treatment for cervical high grade squamous intraepithelial lesion (HSIL). Two hundred and thirty eight patients with HSIL receiving conization in Cancer Hospital, Chinese Academy of Medical Sciences from Dec, 2006 to Jan, 2009 were accrued in our study. All the patients were prospectively observed after conization every 6 months for 3 times or till histologically confirmed recurrence. The items in every visit included pelvic examination, cervical cytology and HPV genotyping. Twenty-one HPV genotypes were detected by PCR-hybridization method. The last follow-up was July 31, 2010, and the median follow-up time was 28.3 months (range 6.5-43.0 months). Kaplan-Meire method as used for analyzed the median recurrent time, and the relationships between HPV status and recurrent disease were calculated by and log-rank test and Cox-regression model. Among the 238 patients, 110 cases (46.2%, 110/238) had positive result of HPV DNA testing at any visit. The most common HPV types detected in follow-up were HPV16 (45.6%), HPV58 (26.5%), and HPV52 (16.9%). There was no correlation between recurrent disease and any individual high risk HPV infections (P>0.05). Seventeen recurrent cases (7.1%) were identified in 238 patients within a median recurrent time of 14.9 months (range 6.0-32.1 months). In univariate analyses, HPV positive at any visit, persistent infection, multiple infection, type specific persistent infection and positive HPV at 18 months after conization were indicators for residual/recurrent disease (P<0.05). In multivariate analysis, only multiple HPV infection (HR=8.6, 95% CI: 1.8-41.7, P=0.008) and type specific persistent HPV infection (HR=5.1, 95% CI: 1.0-24.8, P=0.042) had an elevated risk of recurrent disease. HSIL with multiple HPV infection and type specific persistent HPV infection in follow-up are at high risk of recurrent disease. Patients with HPV turning into negative within 18 months after treatment have a low risk of recurrence.

Human papilloma virus genotyping in women with abnormal cytology

To assess presence of HPV infection and identification of the most common HPV types in patients with abnormal cytology based on the Bethesda system (atypical squamous cells). 81 women with abnormal cytology based on the Bethesda system (atypical squamous cells) were qualified for the study. Material was taken from the cervical canal, the vaginal portion of the cervix and the vagina onto a liquid medium to detect HPV DNA and genotyping of 19 most common oncogenic types of high and medium risk was performed with the Papillomastrip method and for HPV types 6 and 11 with the PCR method. HPV was detected in 53 out of 81 examined women, which accounted for 66%. The most common HPV types were: 6/11 - 23 cases (43% of women with infection), 16 - 23 cases (43% of women with infection), 18 and 33 with 9 cases each (17% of women with infection). Coexistence of 6/11 with 16 or 18 - 13 concerned 15 patients (28% of women with infection) and presence of HPV 16 or 18 was detected in 28 cases (53% of women with infection). Positive HPV type contained in the quadrivalent vaccine against human papillomavirus 6/11 and 16 or 18 was detected in 38 patients (72% of women with infection). 40% of HPV positive women were infected with only one type of the virus, 26%--with two types and 23% with three types. In 81 women with abnormal cytology based on the Bethesda system (atypical squamous cells) within 66% of HPV positive results the most common were type 6/11 (of low oncogenic potential but responsible for anogenital warts) and type 16 of high oncogenic potential.

Distribution of human papillomavirus genotypes in early-stadge cervical adenocarcinoma and its clinical significance

To explore the distribution of high-risk HPV-genotypes in early-stage cervical adenocarcinoma and understand the clinical significance of HPV genotyping. From June 2000 to May 2010, a total of 101 paraffin surgical specimens of cervical adenocarcinoma were genotyped by nested polymerase chain reaction (nested PCR). The associations of HPV18 with clinicopathological parameters and survival were further analyzed. DNA extraction was successfully performed for 96 samples. The HPV-positive rate of early-stage cervical adenocarcinoma was 95.8% (92/96). Two common HPV types were HPV16 (59.4%) and HPV18 (60.4%). The prevalence rates of single, double and multiple HPV infections were 22.9%, 32.3% and 40.6% respectively. The positive rates of lymph node metastasis and vascular involvement with HPV18 infection were 27.6% and 22.4% versus 7.9% and 7.9% for those without HPV18 infection.Univariate analysis showed that positive surgical margin, uterine corpus invasion, lymph node metastasis and HPV18 infection were the predictive factors for poor prognosis of patients with cervical adenocarcinoma. Multivariate analysis revealed that lymph node metastasis was an independent prognostic factor for both disease-free and overall survivals. And uterine corpus invasion was an independent prognostic factor of overall survival for early-stage cervical adenocarcinoma patients. HPV16 and HPV18 are major types responsible for early-stage cervical adenocarcinoma.Infection with HPV18 is prone to lymph node metastasis and vascular involvement.However, there is no correlation with disease-free survival or overall survival.

Are 20 human papillomavirus types causing cervical cancer?

In 2012, the International Agency for Research on Cancer concluded that there was consistent and sufficient epidemiological, experimental and mechanistic evidence of carcinogenicity to humans for 12 HPV types (HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58 and HPV59) for cervical cancer. Therefore, these types were considered as 1A carcinogens. They all belong to the family of the α-Papillomaviridae, in particular to the species α5 (HPV51), α6 (HPV56), α7 (HPV18, HPV39, HPV45, HPV59) and α9 (HPV16, HPV31, HPV33, HPV35, HPV52, HPV58). Less evidence is available for a thirteenth type (HPV68, α7), which is classified as a 2A carcinogen (probably carcinogenic). Moreover, seven other phylogenetically related types (HPV26, HPV53, HPV66, HPV67, HPV68, HPV70 and HPV73) were identified as single HPV infections in certain rare cases of cervical cancer and were considered possibly carcinogenic (2B carcinogens). Recently, Halec et al [7] demonstrated that the molecular signature of HPV-induced carcinogenesis (presence of type-specific spliced E6*| mRNA; increased expression of p16; and decreased expression of cyclin D1, p53 and Rb) was similar in cervical cancers containing single infections with one of the eight afore-mentioned 2A or 2B carcinogens to those in cancers with single infections with group 1 carcinogens. Ninety six percent of cervical cancers are attributable to one of the 13 most common HPV types (groups 1 and 2A). Including the additional seven HPV types (group 2B) added 2.6%, to reach a total of 98.7% of all HPV-positive cervical cancers. From recently updated meta-analyses, it was shown that HPV68, HPV26, HPV66, HPV67, HPV73 and HPV82 were significantly more common in cancer cases than in women with normal cervical cytology, suggesting that for these HPV types, an upgrading of the carcinogen classification could be considered. However, there is no need to include them in HPV screening tests or vaccines, given their rarity in cervical cancers.