Review Article - An overview of human papillomaviruses and current vaccine strategies

Cervical cancer is one of the most common cancers in women worldwide, particularly in developing countries. The viral origin of cervical cancer has been proven beyond any reasonable doubt. Persistent infection with certain subsets of human papillomaviruses is recognized as a necessary cause for the development of cervical cancer. Persistence of oncogenic HPVs, immunodeficiency, high HPV viral load and cofactors like smoking, multiple sex partners and poor nutrition predispose to cervical cancer. Prophylactic vaccines using HPV virus-like particles containing capsid protein L1 have shown protection against disease in animals and are currently undergoing clinical trials. Therapeutic vaccines using HPV E6 and E7 proteins are also being investigated for their ability to remove residual infection

Second Generation Small Molecule Inhibitors of Gankyrin for the Treatment of Pediatric Liver Cancer

Background: Gankyrin, a member of the 26S proteasome, is an overexpressed oncoprotein in hepatoblastoma (HBL) and hepatocellular carcinoma (HCC). Cjoc42 was the first small molecule inhibitor of Gankyrin developed; however, the IC50 values of >50 μM made them unattractive for clinical use. Second-generation inhibitors demonstrate a stronger affinity toward Gankyrin and increased cytotoxicity. The aim of this study was to characterize the in vitro effects of three cjoc42 derivatives. Methods: Experiments were performed on the HepG2 (HBL) and Hep3B (pediatric HCC) cell lines. We evaluated the expression of TSPs, cell cycle markers, and stem cell markers by Western blotting and/or real-time quantitative reverse transcription PCR. We also performed apoptotic, synergy, and methylation assays. Results: The treatment with cjoc42 derivatives led to an increase in TSPs and a dose-dependent decrease in the stem cell phenotype in both cell lines. An increase in apoptosis was only seen with AFM-1 and -2 in Hep3B cells. Drug synergy was seen with doxorubicin, and antagonism was seen with cisplatin. In the presence of cjoc42 derivatives, the 20S subunit of the 26S proteasome was more available to transport doxorubicin to the nucleus, leading to synergy. Conclusion: Small-molecule inhibitors for Gankyrin are a promising therapeutic strategy, especially in combination with doxorubicin

Genital Human Papillomavirus Infection in Indian HIV-Seropositive Men Who Have Sex With Men

BackgroundThe incidence of penile cancer in Indian men is high. Little is known about genital human papillomavirus (HPV) infection in Indian HIV-seropositive men who have sex with men (MSM), a population that may be at particularly high risk for genital HPV infection and, potentially, penile cancer. In this study, we assessed the prevalence and risk factors for genital HPV infection in this population.Design and methodsThree hundred HIV-seropositive MSM were recruited from 2 clinical sites in India. They were tested for genital HPV infection using L1 HPV DNA polymerase chain reaction with probes specific for 29 types and a mixture of 10 additional types. Participants received an interviewer-administered questionnaire that included questions on demographics and behaviors.ResultsHuman papillomavirus data were available from 299 participants. The prevalence of any HPV type in the penis and scrotum was 55% and 54%, respectively. Human papillomavirus type 35 was the most common oncogenic HPV type followed by HPV-16. In multivariate analysis, being the insertive partner with 100+ male partners increased the odds of any penile HPV infection compared with not being insertive with any partners (odds ratio, 2.5; 95% confidence interval, 1.3-5.1). Circumcision was protective against penile HPV infection (odds ratio, 0.39; 95% confidence interval, 0.19-0.76).ConclusionsThe prevalence of penile and scrotal HPV infection was high among Indian HIV-seropositive MSM. The most common oncogenic HPV type in this population, HPV-35, is not included in any currently available HPV vaccines. Insertive anal sex with men and lack of circumcision were the primary risk factors for penile HPV infection in this population

Prevalence of Anal HPV Infection Among HIV-Positive Men Who Have Sex With Men in India

BackgroundIndia has a large population of HIV-positive individuals, including men who have sex with men (MSM), and the incidence of human papillomavirus (HPV)-related cancers is high. In developed countries, HIV-positive MSM exhibit the highest prevalence of anal HPV infection and incidence of anal cancer. Little is known about anal HPV infection in HIV-positive Indian MSM.MethodsWe evaluated 300 HIV-positive MSM from 2 cities in India. Men were tested for anal HPV infection using L1-HPV DNA polymerase chain reaction with probes specific for 29 types and a mixture of 10 additional types. CD4 level and plasma HIV viral load were measured. Participants completed an interviewer-administered questionnaire including a sexual history.ResultsThe prevalence of anal HPV was 95% (95% confidence interval: 91% to 97%). The 3 most common types were HPV 35 (20%), HPV 16 (13%), and HPV 6/11 (13%). History of taking antiretroviral medications decreased risk of anal HPV 16 infection [relative risk (RR): 0.6 (0.4-1.0)]. Having an increased number of vaginal sex partners lowered risk of any anal HPV infection. Ever having receptive sex increased risk of any anal HPV [RR: 1.2 (1.1-1.4)] and anal HPV 16 [RR: 6.5 (1.8-107)].ConclusionsAlmost all Indian HIV-positive MSM had anal HPV infection. The prevalence of HPV 16 was lower and the prevalence of other oncogenic HPV types was higher than in similar populations in North America and Europe. Vaccine-based prevention strategies for HPV infection in India should consider potential differences in HPV type distribution among HIV-infected MSM when designing interventions

Performance of the Aptima High-Risk Human Papillomavirus mRNA Assay in a Referral Population in Comparison with Hybrid Capture 2 and Cytology▿

This study compared the Aptima human papillomavirus (HPV) (AHPV; Gen-Probe Incorporated) assay, which detects E6/E7 mRNA from 14 high-risk types, the Hybrid Capture 2 HPV DNA (HC2; Qiagen Incorporated) test, and repeat cytology for their ability to detect high-grade cervical lesions (cervical intraepithelial neoplasia grade 2+ [CIN2+]) in women referred to colposcopy due to an abnormal Papanicolaou (Pap) smear. A total of 424 clinical specimens, stored in liquid-based cytology (LBC) vials at room temperature for up to 3 years, were tested by repeat cytology, the AHPV assay, and the HC2 test. Assay results were compared to each other and to histology results. The overall agreement between the AHPV assay and the HC2 test was 88.4%. The sensitivity (specificity) of cytology, the HC2 test, and the AHPV assay for the detection of CIN2+ was 84.9% (66.3%), 91.3% (61.0%), and 91.7% (75.0%) and for the detection of CIN3+ was 93.9% (54.4%), 95.7% (46.0%), and 98.2% (56.3%), respectively. Of the disease-positive specimens containing high-risk HPV (HR HPV) DNA as determined by Linear Array (Roche Diagnostics), the AHPV assay missed 3 CIN2 and 1 microfocal CIN3 specimen, while the HC2 test missed 6 CIN2, 4 CIN3, and 1 cervical carcinoma specimen. The AHPV assay had a sensitivity similar to but a specificity significantly higher (P < 0.0001) than the HC2 test for the detection of CIN2+. The AHPV assay was significantly more sensitive (P = 0.0041) and significantly more specific (P = 0.0163) than cytology for the detection of disease (CIN2+)

Association between human papillomavirus DNA and temporal arteritis

<p>Abstract</p> <p>Background</p> <p>To examine the relationship between human papillomavirus (HPV) and giant cell arteritis (GCA) of the temporal artery.</p> <p>Methods</p> <p>The study group consisted of 22 cases of histologically positive/biopsy confirmed GCA. The control groups consisted of 21 histologically negative temporal artery biopsies and fifteen cases of vascular margins of nephrectomies. For detection of the presence of HPV, two methods were used: 1) polymerase chain reaction (PCR) with INNO-LiPA HPV Genotyping Extra, 2) Cervista™ HPV HR. All cases were from the files of the Barnes-Jewish Hospital and Washington University in St. Louis.</p> <p>Results</p> <p>HPV DNA was detected by PCR and genotyping in 16 of 22 (73%) histologically positive cases of GCA and in only five of 21 (24%) histologically negative temporal artery biopsies. Among the vascular margin controls, only three of 15 (20%) were positive for HPV DNA. The second, independent method (Cervista^TM) confirmed the aforesaid results with 100% concordance with the exception of three cases which had low genomic DNA for which it was not possible to perform the test. The differences in HPV positivity between the histologically positive and negative temporal artery biopsies and between the histologically positive temporal artery biopsies and controls were both statistically significant (p = 0.001 and 0.002, respectively).</p> <p>Conclusions</p> <p>The results of our study revealed a statistically significant association between HPV positivity and biopsy confirmed temporal giant cell arteritis GCA (p = 0.001). Further studies are necessary to elucidate the pathophysiology underlying this association.</p

Performance Characteristics and Comparison of Abbott and artus Real-Time Systems for Hepatitis B Virus DNA Quantification ▿

Virological monitoring of hepatitis B virus (HBV) DNA is critical to the management of HBV infection. With several HBV DNA quantification assays available, it is important to use the most efficient testing system for virological monitoring. In this study, we evaluated the performance characteristics and comparability of three HBV DNA quantification systems: Abbott HBV real-time PCR (Abbott PCR), artus HBV real-time PCR with QIAamp DNA blood kit purification (artus-DB), and artus HBV real-time PCR with the QIAamp DSP virus kit purification (artus-DSP). The lower limits of detection of these systems were established against the WHO international standards for HBV DNA and were found to be 1.43, 82, and 9 IU/ml, respectively. The intra-assay and interassay coefficients of variation of plasma samples (1 to 6 log10 IU/ml) ranged between 0.05 to 8.34% and 0.16 to 3.48% for the Abbott PCR, 1.53 to 26.85% and 0.50 to 12.89% for artus-DB, and 0.29 to 7.42% and 0.94 to 3.01% for artus-DSP, respectively. Ninety HBV clinical samples were used for comparison of assays, and paired quantitative results showed strong correlation by linear regression analysis (artus-DB with Abbott PCR, r = 0.95; Abbott PCR with artus-DSP, r = 0.97; and artus-DSP with artus-DB, r = 0.94). Bland-Altman analysis showed a good level of agreement for Abbott PCR and artus-DSP, with a mean difference of 0.10 log10 IU/ml and limits of agreement of −0.91 to 1.11 log10 IU/ml. No genotype-specific bias was seen in all three systems for HBV genotypes A, C, and D, which are predominant in this region. This finding illustrates that the Abbott real-time HBV and artus-DSP systems show more comparable performance than the artus-DB system, meeting the current guidelines for assays to be used in the management of hepatitis B