Graphical abstractStrong expression of p16 in a gingival tumor positive for HPV 18 is depicted. Of the 122 oral cavity cancer cases, joint positivity for HPV 16/18 and p16 INK4a was observed in 33% ...(4/12) of gingival tumors compared to 0% (0/6)–8% (2/26) for other subsites (p = 0.01).
Human papillomavirus (HPV) is a common sexually transmitted infection. Men who have sex with men (MSM) and transgender women (TGW) are at high risk for anal HPV infection and subsequent anal cancer. ...This study assessed the association of partner discordances with prevalent high-risk anal HPV (HRAHPV) among MSM and TGW.
Participants were enrolled in the cross-sectional young men's HPV study of gay, bisexual, and other MSM, and TGW, aged 18 to 26 years, from 2 cities. Participants completed a confidential standardized computer-assisted interview and provided self-collected anal swabs for type-specific HPV DNA testing. Multivariate analyses were conducted for 3 discordances of interest (i.e., partner age, race/ethnicity, and concurrent partner) to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI).
Eight hundred sixty-two participants were included for partner race/ethnicity discordance, 601 for partner age discordance, and 581 for concurrent partner analysis. Most reported being older than 21 years, cisgender male, and gay. Adjusted odds of HRAHPV were not significantly increased among participants reporting partner age discrepancy >10 years (aOR, 0.89; 95% CI, 0.51-1.56), partner race/ethnicity discordance (aOR, 0.88; CI, 0.62-1.24), or partner with concurrent partners (aOR, 0.85; 95% CI, 0.50-1.42), compared with those who did not.
This analysis did not identify any partner discordances associated with HRAHPV. Because HPV infection can persist for years, sexual mixing patterns with early partners might be more relevant than the most recent sex partner. Prevalence of HRAHPV was high and could be preventable by preexposure vaccination, as recommended for everyone through age 26 years including MSM and TGW.
Since 2006, the US human papillomavirus (HPV) vaccination program has led to decreases in HPV infections caused by high-risk vaccine-targeted HPV types (HPV 16/18). We assessed differences in ...high-risk HPV prevalence by cervical cytology result among 20- to 24-year-old persons participating in routine cervical cancer screening in 2015-2017 compared with 2007.
Residual routine cervical cancer screening specimens were collected from 20- to 24-year-old members of 2 integrated healthcare delivery systems as part of a cross-sectional study and were tested for 37 HPV types. Cytology results and vaccination status (≥1 dose) were extracted from medical records. Cytology categories were normal, atypical squamous cells of undefined significance, low-grade squamous intraepithelial lesions (SIL), or high-grade SIL/atypical squamous cells cannot exclude high-grade SIL. Prevalences of HPV categories (HPV 16/18, HPV 31/33/45/52/58, HPV 35/39/51/56/59/66/68) were estimated by cytology result for 2007 and 2015-2017.
Specimens from 2007 (n = 4046) were from unvaccinated participants; 4574 of 8442 specimens (54.2%) from 2015-2017 were from vaccinated participants. Overall, HPV 16/18 positivity was lower in 2015-2017 compared with 2007 in all groups: high-grade SIL/atypical squamous cells cannot exclude high-grade SIL, 16.0% vs 69.2%; low-grade SIL, 5.4% vs 40.1%; atypical squamous cells of undefined significance, 5.0% vs 25.6%; and normal, 1.3% vs 8.1%. Human papillomavirus 31/33/45/52/58 prevalence was stable for all cytology groups; HPV 35/39/51/56/59/66/68 prevalence increased among low-grade SIL specimens (53.9% to 65.2%) but remained stable in other groups.
Prevalence of vaccine-targeted high-risk HPV types 16/18 was dramatically lower in 2015-2017 than 2007 across all cytology result groups while prevalence of other high-risk HPV types was mainly stable, supporting vaccine impact with no evidence of type replacement.
As immunization programs for human papillomavirus (HPV) are implemented more widely around the world, interest is increasing in measuring their impact. One early measurable impact of HPV vaccine is ...on the prevalence of specific HPV types in a population. In low‐resource settings, a potentially attractive strategy would be to monitor HPV prevalence using clinical cervical cancer screening test results to triage specimens for HPV typing. We assessed this approach in a nationally representative population of U.S. females aged 14–59 years. Using self‐collected cervico‐vaginal swab specimens from 4,150 women participating in the National Health and Nutrition Examination Survey during 2003–2006, we evaluated type‐specific HPV prevalence detected by the Roche linear array (LA) research test on all specimens, compared with type‐specific HPV prevalence detected by LA conducted only on specimens positive by the digene hybrid capture 2 (HC‐2) clinical test. We calculated weighted prevalence estimates and their 95% confidence intervals (CIs), and examined relative type‐specific HPV prevalence according to the two testing approaches. The population prevalence of oncogenic HPV vaccine types 16/18 was 6.2% (CI:5.4–7.1) by LA if all specimens were tested, and 2.4% (CI:1.9–3.0) if restricted to positive HC‐2. Relative prevalence of individual HPV types was similar for both approaches. Compared with typing all specimens, a triage approach would require testing fewer specimens, but a greater reduction in HPV prevalence or a larger group of specimens would be needed to detect vaccine impact. Further investigation is warranted to inform type‐specific HPV monitoring approaches around the world.
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The impact of human papillomavirus (HPV) immunization on cervical cancer incidence in populations of vaccinated women may not be apparent for decades, complicating evaluation of the early effectiveness of HPV vaccination programs. Evidence presented here indicates that it may be possible to do this by performing HPV‐type analysis on cervical specimens, since one of the earliest measurable effects of HPV vaccine in a population should be a reduction in specific HPV types. The triage of cervical specimens for HPV typing based on results of a clinical HPV test such as the digene hybrid capture 2 (HC‐2) could complement existing cervical cancer screening programs and reduce overall testing costs, and therefore may be appealing for use in low‐resource settings.
Background. Anal cancer rates are higher for human immunodeficiency virus (HIV)–infected adults than for uninfected adults. Limited published data exist characterizing the incidence of precursor ...lesions detected by anal cytology. Methods. The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy was a prospective cohort of 700 HIV-infected participants in 4 US cities. At baseline and annually thereafter, each participant completed a behavioral questionnaire, and healthcare professionals collected anorectal swabs for cytologic examination and human papillomavirus (HPV) detection and genotyping. Results. Among 243 participants with negative baseline results of anal cytology, 37% developed abnormal cytology findings (incidence rate, 13.9 cases/100 person-years of follow-up; 95% confidence interval CI, 11.3–16.9) over a median follow-up duration of 2.1 years. Rates among men having sex with men, among women, and among men having sex with women were 17.9 cases/person-years of follow-up (95% CI, 13.9–22.7), 9.4 cases/person-years of follow-up (95% CI, 5.6–14.9), and 8.9 cases/person-years of follow-up (95% CI, 4.8–15.6), respectively. In multivariable analysis, the number of persistent high-risk HPV types (adjusted hazard ratio aHR, 1.17; 95% CI, 1.01–1.36), persistent high-risk HPV types except 16 or 18 (aHR, 2.46; 95% CI, 1.31–4.60), and persistent types 16 or 18 (aHR, 3.90; 95% CI, 1.78–8.54) remained associated with incident abnormalities. Conclusions. The incidence of abnormal anal cytology findings was high and more likely to develop among persons with persistent high-risk HPV.
We conducted a baseline study of human papillomavirus (HPV) type prevalence in invasive cervical cancers (ICCs) using data from 7 cancer registries (CRs) in the United States. Cases were diagnosed ...between 1994 and 2005 before the implementation of the HPV vaccines.
Cancer registries from Florida, Kentucky, Louisiana, Michigan, Hawaii, Iowa, and Los Angeles, California identified eligible ICC cases and obtained sections from representative blocks of archived tumor specimens for DNA extraction. All extracts were assayed by linear array and, if inadequate or HPV negative, retested with INNO-LiPA Genotype test. Clinical and demographic factors were obtained from the CRs and merged with the HPV typing data to analyze factors associated with different types and with HPV negativity.
A total of 777 ICCs were included in this analysis, with broad geographic, age, and race distribution. Overall, HPV was detected in 91% of cases, including 51% HPV-16, 16% HPV-18 (HPV-16-negative), and 24% other oncogenic and rare types. After HPV-16 and -18, the most common types were 45, 33, 31, 35, and 52. Older age and nonsquamous histology were associated with HPV-negative typing.
This study provides baseline prevaccine HPV types for postvaccine ICC surveillance in the future. HPV-16 and/or -18 were found in 67% of ICCs, indicating the potential for vaccines to prevent a significant number of cervical cancers.
Strong expression of p16 in a gingival tumor positive for HPV 18 is depicted. Of the 122 oral cavity cancer cases, joint positivity for HPV 16/18 and p16INK4a was observed in 33% (4/12) of gingival ...tumors compared to 0% (0/6)–8% (2/26) for other subsites (p = 0.01).
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•HPV DNA and p16INK4a were each detected in ∼30% of oral cavity cases but were poorly correlated.•HPV 16, found in 22% of tumors, was the most frequently detected of seven genotypes.•Joint positivity for HPV 16 and/or 18 and p16INK4a was observed in 7% of cases.•HPV 16/18 and p16INK4a positivity was highest in gingival tumors (33%) and in more recently diagnosed cases.•Neither HPV DNA nor p16INK4a were associated with overall survival.
The role of HPV in oral cavity cancers was investigated using two markers of viral exposure.
HPV DNA and p16INK4a expression were evaluated in tumor tissue from a U.S. population-based sample of 122 invasive oral cavity cancer cases.
HPV DNA was detected in 38 of 122 (31%) oral cavity tumors. Seven genotypes were detected including HPV 16, which was found in 22% of tumors. p16INK4a was expressed in 30% of tumors and was poorly correlated with HPV DNA detection (Kappa <0.1). Joint positivity for HPV 16 and/or 18 and p16INK4a was observed in only 7% of cases. When comparing cases diagnosed in 1993–1999 and in 2000–2004, positivity for HPV DNA 16/18 increased from 19% to 39% (p = 0.02) and joint HPV 16/18 – p16INK4a positivity increased from 0% to 12% (p = 0.01). For gingival tumors, HPV 16 and/or 18 positivity was 67% compared to 11–38% for other sites (p = 0.02); joint HPV 16/18 – p16INK4a positivity was 33% compared to 0–8% for other sites (p = 0.01). The association of HPV with gingival tumors and more recent diagnosis period remained after adjustment for age and stage (p < 0.05). Neither HPV DNA nor p16INK4a were associated with overall survival.
Based on both HPV DNA and p16INK4a, HPV is etiologically linked to a limited subset of oral cavity cancers. However, the role of HPV in oral cavity cancer may vary widely by subsite and may have increased over time, similar to trends observed for oropharyngeal cancer.
Abstract Objective To test the hypothesis that self-collected urine could be used to detect high-risk human papillomavirus (HPV) DNA with sensitivity and specificity comparable to those of standard ...cervical testing. Methods Women attending a gynecology clinic for evaluation of abnormal cytology were recruited. Fifty-two participants (21–60 years of age) collected urine samples, and clinicians collected cervical brush samples. When appropriate, cervical biopsies were obtained during colposcopy. HPV detection and typing were performed on DNA extracts from each sample, using commercial reagents for L1 consensus polymerase chain reaction (PCR) and type-specific hybridization. HPV 16 viral load was determined by quantitative PCR in HPV 16-positive samples. A diagnostic test analysis was conducted for urine samples. Results Fifty paired samples were analyzed, with 76% agreement between samples. The 12 discrepant pairs were all urine negative/cervix positive. The most common HPV types detected were 16, 51, 53, and 62. The urine test correctly identified 100% of the uninfected and 65% of the infected patients. Conclusion The results indicate that HPV DNA detection using urine is less sensitive than cervical sampling in a population with abnormal cytology. Further exploration is warranted to determine clinical utility when other options are unavailable.
Human papillomavirus (HPV) 52 is one of the most frequent high risk HPV types found in cervical and anal infections. Reliable and well characterized methods for HPV 52 detection are therefore of ...great importance. Unfortunately one of the most widely used commercially available HPV typing assays, the Roche Linear Array (LA), detects type 52 only through its XR probe which cross-reacts with types 33, 35 and 58 and fails to give unambiguous detection of HPV 52.
To address this problem a real-time TaqMan PCR assay for HPV 52 targeting the E6/E7 region was developed and validated, which can be applied as robust duplex assay simultaneously detecting beta-globin as genomic control and reference or as highly sensitive single target detection assay.
Optimized primer and probe concentrations produced linear PCR amplifications over seven logs of targets (10(1) - 10(7)). The detection limit for HPV 52 was reproducibly at 10 copies per reaction for the duplex assay format and 5 copies for the single-plex format. The assay was very type-specific and no amplification signal was observed with 10(7) copies of the related HPV33, 35, and 58 DNA. Of 89 samples that tested unambiguously positive for HPV 52 in the LA, 75 were confirmed in the duplex format and 88 in the single-plex format. An additional 100 samples negative for HPV 52 in LA were all negative in both HPV 52 real-time PCR assay formats.
These results indicate 92.6% and 99.5% accuracy relative to LA for the duplex and single-plex formats, respectively. In ongoing testing of 18,484 from various studies, 10.8% required the HPV52 TaqMan assay to unequivocally determine the status. Including the HPV 52 duplex assay provides the ability to monitor variations in the cell yield in various methods of sample collection and processing. This additional information is useful in QC monitoring of epidemiologic studies.
In August 2014, the Viral Special Pathogens Branch of the US Centers for Disease Control and Prevention established a field laboratory in Sierra Leone in response to the ongoing Ebola virus outbreak. ...Through March 2015, this laboratory tested >12 000 specimens from throughout Sierra Leone. We describe the organization and procedures of the laboratory located in Bo, Sierra Leone.
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