Can genital-tract human papillomavirus infection and cervical cancer be prevented with a vaccine?

Human papillomavirus (HPV) infection is the cause of squamous cell carcinoma of the uterine cervix. This causative relationship has provided the rationale and incentive for development of a prophylactic vaccine. Such a vaccine, if found to be effective, could reduce the need for cervical cancer screening and have a profound effect on the incidence of cervical and other anogenital cancers. This review begins by examining the basic biological and epidemiological principles relevant to the development of HPV preventative vaccines. It then summarises studies examining the use of vaccines to prevent HPV infection in animals and humans, and, finally, discusses some of the unanswered issues surrounding vaccine development against HPV infection and cervical cancer

Evidence for cross-protection but not type-replacement over the 11 years after human papillomavirus vaccine introduction

Examination of cross-protection and type replacement after human papillomavirus (HPV) vaccine introduction is essential to guide vaccination recommendations and policies. The aims of this study were to examine trends in non-vaccine-type HPV: 1) genetically related to vaccine types (to assess for cross-protection) and 2) genetically unrelated to vaccine types (to assess for type replacement), among young women 13-26 years of age during the 11 years after HPV vaccine introduction. Participants were recruited from a hospital-based teen health center and a community health department for four cross-sectional surveillance studies between 2006 and 2017. Participants completed a survey that assessed sociodemographic characteristics and behaviors, and cervicovaginal swabs were collected and tested for 36 HPV genotypes. We determined changes in proportions of non-vaccine-type HPV prevalence and conducted logistic regression to determine the odds of infection across the surveillance studies, propensity-score adjusted to control for selection bias. Analyses were stratified by vaccination status. Among vaccinated women who received only the 4-valent vaccine (n = 1,540), the adjusted prevalence of HPV types genetically related to HPV16 decreased significantly by 45.8% (adjusted odds ratio [AOR] = 0.48, 95% confidence interval [CI] = 0.31-0.74) from 2006-2017, demonstrating evidence of cross-protection. The adjusted prevalence of HPV types genetically related to HPV18 did not change significantly (14.2% decrease, AOR = 0.83, 95% CI = 0.56-1.21). The adjusted prevalence of HPV types genetically unrelated to vaccine types did not change significantly (4.2% increase, AOR = 1.09, CI = 0.80-1.48), demonstrating no evidence of type replacement. Further studies are needed to monitor for cross-protection and possible type replacement after introduction of the 9-valent HPV vaccine

The Human Papillomavirus Type 11 E1∧E4 Protein Is Phosphorylated in Genital Epithelium

AbstractThe most abundant viral transcript in human papillomavirus (HPV) 11-infected xenograft tissue has been shown to encode the E1∧E4 protein. The function of E1∧E4 protein has not been determined. Several potential phosphorylation sequence motifs were identified in the HPV 11 E1∧E4 protein, including potential sites of phosphorylation by mitogen-activated protein kinase (MAPK), cAMP-dependent protein kinase (PKA), casein kinase II, and protein kinase C. To test phosphorylation of the HPV 11 E1∧E4 protein, a soluble maltose binding protein (MBP) fusion was produced in Escherichia coli. Only MAPK and PKA phosphorylated the E1∧E4 protein. Phosphoamino acid analysis showed that one or more threonine residues were phosphorylated by MAPK, and both serine and threonine residues were phosphorylated by PKA. MBP–E1∧E4 mutant proteins were designed to delineate the E1∧E4 phosphoacceptor residues. MAPK was shown to phosphorylate E1∧E4 on threonine 53 within a MAPK consensus phorphorylation sequence motif. PKA was shown to phosphorylate E1∧E4 at two residues: threonine 36 within a consensus motif and serine 44 within a variant of the PKA consensus phosphorylation sequence motif. HPV 11-infected human genital tissue grown as a xenograft in an athymic mouse was labeled with [32P]orthophosphate. Phosphoamino acid analysis of E1∧E4 protein immunoprecipitated from 32P-labeled tissue revealed that both serine and threonine residues were phosphorylated. Analysis by liquid chromatography–mass spectrophotometry was consistent with phosphorylation of residues within the PKA and MAPK phosphorylation sequence motifs. Expression of E1∧E4 protein containing phosphorylation substitution mutations showed that the PKA mutant did not differ from wild-type E1∧E4 protein in intracellular distribution. In contrast, the MAPK mutant did not localize exclusively to the cytoplasm nor did it colocalize with wild-type E1∧E4 protein. We conclude that HPV 11 E1∧E4 protein is phosphorylated in vitro and in vivo. Our data are consistent with phosphorylation of HPV 11 E1∧E4 protein by MAPK and PKA in infected tissue

Association of HPV types 6, 11, 16, and 18 DNA detection and serological response in unvaccinated adolescent women

Antibodies directed against the human papillomavirus (HPV) L1 protein are detected in approximately 70% of individuals with HPV infections. The factors associated with a serological response are not characterized. It is hypothesized that the HPV viral load, duration of detection, or both would be associated with seropositivity in adolescent women. Adolescent women (n = 117), ages 15-17 at enrolment were followed for a mean of 6.2 years. Quarterly vaginal swabs (mean 22 per participant) were used to identify HPV 6, 11, 16, or 18 DNA (Roche PCR/Linear Array). Type-specific HPV infection was defined as ≥2 positive assays. To approximate viral load, Roche PCR/Linear Array test strips were scored visually based on the strength of signal relative to beta-globin controls. Sera collected near the end of study were tested by cLIA. Regression models were fit to assess associations between strength of signal (as represented by mean and cumulative strength of signal), duration of HPV detection, seropositivity, and serotiter. Detection of HPV DNA was associated with seropositivity for four types combined and for types 6, 16, and 18. Overall, 70.1% of DNA positive episodes were associated with type-specific seropositivity. The cumulative HPV DNA signal strength during periods of HPV detection for types 6, 11, 16, and 18 combined was associated with seropositivity (OR = 1.21, 95% CI 1.02-1.44 P = 0.026). No other HPV DNA predictors were found to be associated with seropositivity or serotiter

Epidemiology of Any and Vaccine-Type Anogenital Human Papillomavirus Among 13-26-Year-Old Young Men After HPV Vaccine Introduction

PURPOSE: The aims of this study were to determine prevalence of and factors associated with any human papillomavirus (HPV) and vaccine-type HPV among young men after vaccine introduction, stratified by vaccination status. METHODS: Young men were recruited from clinical sites from 2013 to 2015, completed a survey, and were tested for 36 anogenital HPV types. We determined factors associated with ≥1 HPV type among all participants, and vaccine-type HPV (HPV6, 11, 16, and/or 18) among all, vaccinated and unvaccinated participants, using multivariable regression. RESULTS: Mean age was 21.5 years and 26% had received at least one HPV vaccine dose. HPV prevalence was lower in vaccinated versus unvaccinated young men (50.5% vs. 62.6%, p = .03). HPV positivity was discordant by anogenital site. At both sites, 59.4% were positive for ≥1 HPV type and 26.0% for ≥1 4-valent vaccine type. In multivariable logistic regression, factors associated with ≥1 HPV type among all participants were frequency of oral sex (odds ratio [OR] = 1.80, 95% confidence interval [CI] = 1.00-3.24), recent smoking (OR = 1.84, CI = 1.17-2.90), and sexually transmitted infection history (OR = 1.56, CI = 1.02-2.38). Factors associated with vaccine-type HPV among all participants were white versus black race (OR = 1.91, CI = 1.10-3.34) and gonorrhea history (OR = 2.52, CI = 1.45-4.38); among vaccinated participants were private versus Medicaid insurance (OR = 5.6, CI = 1.46-20.4) and private versus no insurance (OR = 15.9, CI = 3.06-83.3); and among unvaccinated participants was gonorrhea history (OR = 1.83, CI = 1.03-3.24). CONCLUSIONS: Anogenital HPV prevalence was high and vaccination rates low among young men 2-4 years after vaccine introduction, underscoring the urgency of increasing vaccination rates and vaccinating according to national guidelines

The Grizzly, February 2, 2006

New Member Education Begins Another Season at Ursinus • What Happened to the Kreme? • CAB\u27s Events in the Spring of 2006 • Bomberger Cam • Sigma Xi Lecture at Olin • Virginity Vexing • Dancer and Cultural Historian to Speak at Ursinus • Pre-departure Paris • Ursinus Gets Greener by Doing More than Landscaping • Dealing with Stress • Opinions: There are no Maids Here; Return of Open Mic Night; The New Pornographers Break Through with Twin Cinema • Bears Veto Diplomats • Daley\u27s Lay-up Beats Diplomatshttps://digitalcommons.ursinus.edu/grizzlynews/1704/thumbnail.jp

Human papillomavirus seroprevalence and seroconversion following baseline detection of nine human papillomavirus types in young women

Background: Estimates of the humoral immune response to incident human papillomavirus (HPV) infections are limited. Methods: In this post hoc analysis of 3875 women aged 16-23 years from a 4-valent HPV vaccine trial (NCT00092482), HPV seroprevalence on day 1 was measured with a 9-valent HPV (HPV 6/11/16/18/31/33/45/ 52/58) competitive Luminex immunoassay and compared with cervical/external genital HPV detection by po-lymerase chain reaction. In the control group, among women who were HPV DNA-negative on day 1, sero-conversion following initial HPV detection was estimated using Kaplan-Meier methods. Results: Type-specific HPV seropositivity among women with no day 1 cervical/external genital HPV detection was 0.6%-3.6%. Women with any 9-valent HPV (9vHPV) cervical/external genital detection (796/3875; 20.5%) had concordant seropositivity ranging from 13.4% (HPV 45) to 38.5% (HPV 6). Among women in the control group who were negative for all HPV types on day 1, seroconversion by month 30 after initial detection ranged from 29% (HPV 45) to 75% (HPV 16). Conclusions: Humoral immune response to HPV is variable and dynamic, depending on type-specific exposure. This longitudinal analysis provides insight into the relationship between incident infection and seropositivity

The Grizzly, January 26, 2006

Dr. Martin Luther King Jr. Day Observed and Celebrated at Ursinus • Renowned Rodin Exhibit Premieres in Berman Museum • Ursinus Establishes Salinger Scholarship and Offers Salinger\u27s Dorm Room • Francophone Film Festival at Ursinus • Artist to Perform in Lansdale • Uninvited Guests • Excellent Opportunity is Available through Career Services • Turning Over a New Leaf • My Personal Pact Against Segregation • Weigh in on Proper Fitness Center Etiquette • Opinions: Whole Foods Market Harvests Natural Energy; The New Prejudice: The Unruly Child? • Fiery Free Throws from Fureyhttps://digitalcommons.ursinus.edu/grizzlynews/1703/thumbnail.jp

The Grizzly, February 23, 2006

Possibility of Honor Code Comes Under Review Again at Ursinus • Date Auction Raises Money for Airband Charity • WVOU: Preview of the Semester\u27s Events • Countdown to Relay Continues • Batteries Included • Airband Begins a Successful Year • A Vitamin a Day Keeps the Doctor Away • Kwan Bows out of Olympics • Opinions: How Did You Celebrate Black History Month?; Apple Twists Unexpected in Extraordinary Machine • Crown Hopes for Royal Family • History Made as Bears Win 4th CC Titlehttps://digitalcommons.ursinus.edu/grizzlynews/1707/thumbnail.jp

The Grizzly, February 9, 2006

Preview of Black History Month at Ursinus • Wellness Center Relocated • Higher Education Lobbyist to Speak • Relay for Life Kick-off Exhibits Large Turnout and Hope for Event • Scents and Sensibility • Le Metropolitan • Rodin Curator to Lecture • Residence Life Creates Exciting New Housing Options • Monkey Business Takes on a Whole New Meaning • Getting Around: Why Biking is Better • Opinions: Real Love, I\u27m Looking for Real Love; Many Faces of Beck; Fighting for a Spot: The Pains of Parking on Campus • Dynasty! 20 Straight CC Winshttps://digitalcommons.ursinus.edu/grizzlynews/1705/thumbnail.jp