Search

Author(s): Wagner, Sarah; Roberson, David; Boland, Joseph; Kreimer, Aimee R; Yeager, Meredith; Cullen, Michael; Mirabello, Lisa; Dunn, S Terence; Walker, Joan; Zuna, Rosemary; Porras, Carolina; Cortes, Bernal; Sampson, Joshua; Herrero, Rolando; Rodriguez, Ana Cecilia; Quint, Wim; Van Doorn, Leen-Jan; CVT Group; Hildesheim, Allan; Schiffman, Mark; Wentzensen, Nicolas | Abstract: BackgroundHuman papillomaviruses (HPV) cause over 500 000 cervical cancers each year, most of which occur in low-resource settings. Human papillomavirus genotyping is important to study natural history and vaccine efficacy. We evaluated TypeSeq, a novel, next-generation, sequencing-based assay that detects 51 HPV genotypes, in 2 large international epidemiologic studies.MethodsTypeSeq was evaluated in 2804 cervical specimens from the Study to Understand Cervical Cancer Endpoints and Early Determinants (SUCCEED) and in 2357 specimens from the Costa Rica Vaccine Trial (CVT). Positive agreement and risks of precancer for individual genotypes were calculated for TypeSeq in comparison to Linear Array (SUCCEED). In CVT, positive agreement and vaccine efficacy were calculated for TypeSeq and SPF10-LiPA.ResultsWe observed high overall and positive agreement for most genotypes between TypeSeq and Linear Array in SUCCEED and SPF10-LiPA in CVT. There was no significant difference in risk of precancer between TypeSeq and Linear Array in SUCCEED or in estimates of vaccine efficacy between TypeSeq and SPF10-LiPA in CVT.ConclusionsThe agreement of TypeSeq with Linear Array and SPF10-LiPA, 2 well established standards for HPV genotyping, demonstrates its high accuracy. TypeSeq provides high-throughput, affordable HPV genotyping for world-wide studies of cervical precancer risk and of HPV vaccine efficacy.

Background Factors that lead human papillomavirus (HPV) infections to persist and progress to cancer are not fully understood. We evaluated co-factors for acquisition, persistence, and progression of non–HPV-16/18 infections among HPV-vaccinated women. Methods We analyzed 2153 women aged 18–25 years randomized to the HPV-vaccine arm of the Costa Rica HPV Vaccine Trial. Women were HPV DNA negative for all types at baseline and followed for approximately 11 years. Generalized estimating equation methods were used to account for correlated observations. Time-dependent factors evaluated were age, sexual behavior, marital status, hormonally related factors, number of full-term pregnancies (FTPs), smoking behavior, and baseline body mass index. Results A total of 1777 incident oncogenic non–HPV-16/18 infections were detected in 12 292 visits (average, 0.14 infections/visit). Age and sexual behavior–related variables were associated with oncogenic non–HPV-16/18 acquisition. Twenty-six percent of incident infections persisted for ≥1 year. None of the factors evaluated were statistically associated with persistence of oncogenic non–HPV-16/18 infections. Risk of progression to Cervical Intraepithelial Neoplasia grade 2 or worst (CIN2+) increased with increasing age (P for trend = .001), injectable contraceptive use (relative risk, 2.61 [95% confidence interval, 1.19–5.73] ever vs never), and increasing FTPs (P for trend = .034). Conclusions In a cohort of HPV-16/18–vaccinated women, age and sexual behavior variables are associated with acquisition of oncogenic non–HPV-16/18 infections; no notable factors are associated with persistence of acquired infections; and age, parity, and hormonally related exposures are associated with progression to CIN2+.

Vulvar cancer is rare, accounting for approximately 4% of gynecological malignancies worldwide [1]. However, the incidence of vulvar cancer has been increasing, particularly in young women [2, 3]. In the United States from 2000 to 2009, the incidence of vulvar cancer has significantly increased among both white and African American women; 1.4% and 0.9% annual percentage change, respectively [3]. This increase is believed to be due to a rise in human papillomavirus (HPV) infection [2, 4–6]. Worldwide, it is estimated that HPV infection is the causative agent in approximately 43% of vulvar cancers [7]. HPV 16 and 18 infections combined account for 93% of HPV-associated vulvar cancers [8]; thus, prophylactic vaccination has the potential to reduce the incidence of vulvar cancer. Two vaccines prevent HPV 16 and 18 infections at the cervix: the bivalent HPV16/18 vaccine Cervarix®, GlaxoSmithKline Vaccines [GSK]) [9] and the quadrivalent HPV6/11/16/18 vaccine (Gardasil™, Merck and Co, Inc) [10]. Data presented in abstract form for the bivalent vaccine reported a 75% reduction in HPV16/18-associated vulvar/vaginal precursor lesions (a combined endpoint) among vaccinated women compared to controls [11]. For the quadrivalent vaccine, high (>95%) vaccine efficacy (VE) against HPV16/18-associated vulvar intraepithelial neoplasia grades 1, 2, and 3 was demonstrated [10], garnering an indication from the US Food and Drug Administration (FDA) for prevention of vulvar cancer. VE against HPV16/18 infections at the vulva has yet to be reported. Efficacy against HPV16/18-associated vulvar lesions was demonstrated by both pharmaceutical vaccine trials using HPV DNA testing of vulvar lesions, which represented a small subset of the total trial population [10, 11]. Given that VE against HPV-associated lesions is the result of prevention of HPV infection, we reasoned that use of a virologic endpoint for the estimation of vulvar VE would provide additional novel information on an intermediate endpoint on the pathway to cancer. Likewise, perhaps due to the rarity of HPV-associated vulvar cancer, only 6 studies have been published on the epidemiology of vulvar HPV infection in cancer-free women [12–17] and only 1 study reported risk factors associated with high-risk HPV infection of the vulva [17]. To address the limited knowledge of vulvar VE as well as the epidemiology of vulvar HPV infection, we implemented a vulvar specimen collection at the final (year 4), randomized blinded study visit of the Costa Rica Vaccine Trial (CVT). The goals of this value-added analysis were to (1) estimate the reduction of prevalent HPV16/18 infections at the vulva compared to cervix among HPV vaccinated women compared to controls 4 years after vaccination, and (2) characterize the prevalence of and risk factors for vulvar HPV infection in the control arm of this study population.

Anal cancer is rare, with age-standardized annual incidence rates of 0.2–1.4 cases/100 000. Rates are higher in women and vary by geographical location [1]. During the past 3–4 decades, a significant increase in anal cancer rates has been reported for both sexes in many developed countries [2–4]. Several epidemiological studies suggest that oncogenic human papillomavirus (HPV) infection, a necessary cause of cervical cancer, is the main cause of anal cancer and its precursor lesions [5–9]. A recent meta-analysis [10] of 29 anal cancer studies estimated that HPV DNA was present in 84% of anal cancers worldwide and confirmed previous observations that HPV-16 was the most frequent genotype associated with anal carcinoma (>75% of cases), followed by HPV-18 and HPV-33 (approximately 10% of cases combined). Research on the natural history of anal HPV infection suggests that sexual behavior is the main risk factor [11–16]. However, the majority of the research to date has focused on high-risk groups, such as men who have sex with men (MSM) or human immunodeficiency virus–infected male and female subjects. Thus, little is known about anal HPV infection in healthy women. Only one prospective study, which occurred in Hawaii [16], investigated anal HPV infection among healthy women (age range, 18–55 years). The overall prevalence of anal HPV infection was 27%. During follow-up, the vast majority (approximately 90%) of infections cleared by 1 year [17]. The epidemiology of anal HPV infections might vary by age, geographical location, and other characteristics; thus, additional epidemiological studies are warranted to better understand the natural history of anal HPV infection in other general populations. The aim of the present study was to estimate prevalence of individual anal HPV types in young healthy women in Costa Rica and to characterize risk factors for anal HPV infection in this group.

Background. Little is known about the prevalence of human papillomavirus (HPV) infection in young adults in Asia. Methods. We invited female and male students in Busan, South Korea, to participate in a survey that included, for females, self-collection of vaginal cells and, for males, physician-performed collection of exfoliated genital cells. The prevalences of 25 HPV types were evaluated, by a polymerase chain reaction-based assay, in 672 female students (median age, 19 years) and in 381 male students (median age, 22 years). Results. HPV DNA was detected more frequently in female students (15.2%) than in male students (8.7%); in both sexes, high-risk HPV types were predominant. Among sexually active students, HPV prevalence was 38.8% in females and 10.6% in males. In female students, currently smoking cigarettes and having multiple lifetime sex partners were the strongest risk factors for HPV infection; in male students, associations between HPV prevalence and sexual habits were similar to those in female students but never attained statistical significance. Conclusions. Young women in South Korea start having penetrative sexual intercourse relatively late (median age, 18 years), but, once they begin, HPV prevalence quickly rises to levels comparable with those found in university students in the United States and in northern Europe. The high rate of participation in our study suggests that trials of new vaccines against HPV may be feasible among university students in South Korea.

Studies have reported an increased incidence of oropharyngeal cancer predominantly among younger birth cohorts in developed countries [1–8]. This upsurge has been attributed to an increase in human papillomavirus (HPV)–driven oropharyngeal cancers [7], primarily due to HPV-16 infection, which accounts for approximately 90% of HPV-positive oropharyngeal cancers [9, 10]. Detection of oral HPV-16 DNA in oral rinse/gargle samples was associated with a substantial increase in the odds of prevalent oropharyngeal cancer [10]. However, little is known about the epidemiology of oral HPV infection. To our knowledge, only 3 large studies (≥1000 participants), based predominantly in the United States, have examined the epidemiology of oral HPV in healthy individuals [11–13]. Prevalence of any type of oral HPV ranged from approximately 2% to 7%; reported risk factors included increasing age, male sex, higher number of sexual partners, and tobacco use [11–13]. Additionally, these studies focused on detection of oral mucosal HPV types from the genus Alphapapillomavirus. Yet, recent evidence suggests that the oral region of healthy individuals also contains a high prevalence of cutaneous HPV types (predominantly Betapapillomavirus and Gammapapillomavirus), which have previously been thought to uniquely infect keratinized epithelium and are associated with skin lesions [14–18]. Few studies have reported the prevalence of oral HPV in resource-poor regions. In Latin America, only 5 small studies (

Information on the prevalence of cervical infection with different human papillomavirus (HPV) types among young women is essential to support the introduction of HPV vaccine in Uganda.Cross-sectional findings are presented from a cohort study of 1,275 sexually active women aged 12-24 years seeking health services at a clinic for teenagers in Kampala, Uganda. We assessed the presence of 39 HPV types by use of highly sensitive polymerase chain reaction assays.The prevalence of HPV infection was 74.6%, and the prevalence of human immunodeficiency virus infection was 8.6%. High-risk HPV types were found in 51.4% of women, and the most frequently detected high-risk types were, in decreasing order, HPV 52, 51, 18, and 16. A total of 71.8% of the women who were positive for HPV 16 and/or 18 were also infected with other high-risk HPV types. HIV-positive women had a higher prevalence of HPV infection (87.8% vs 73.2%) and of multiple-type infections (64.6% vs 37.3%), compared with HIV-negative women. Employment in the tertiary sector, lifetime number of sexual partners, concurrent pregnancy, and the presence of genital warts were significantly associated with HPV positivity.The prevalence of HPV infection is high among young women in Kampala, Uganda. Clinics for teenagers provide an opportunity to monitor the impact of HPV vaccines and, possibly, to catch up unvaccinated young women who have recently become sexually active.

A polymerase chain reaction (PCR)-mediated genotyping assay for Candida albicans has been developed. By amplification of genomic regions bordered by eukaryotic or prokaryotic repeat-like motifs, differences between C. albicans isolates can be determined. The resolution of this typing procedure is at least as good as that of other genotypic assays. To ascertain the epidemiologic and clinical usefulness of this PCR genotyping, a retrospective analysis of serial C. albicans isolates from neutropenic adults treated with fluconazole was done. By PCR genotyping, 40 strains were detected in 24 patients. Eighteen C. albicans strains were found on multiple samplings in individual patients. It appears that most patients remain colonized with a C. albicans strain of constant genotypic characteristics. However, exceptions were observed. In 7 (29%) of 24 patients, strains deviating from the most frequently encountered type could be identified. All but 1 strain remained susceptible to fluconazole in vitro after treatment in vivo. It was not possible to demonstrate a relation of genotypic variation and antifungal susceptibility changes.