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Background: Among women whose cervical specimens tested positive for high-risk human papillomaviruses (hrHPV) via the Hybrid Capture 2 assay in the Canadian Cervical Cancer Screening Trial (CCCaST), we assessed hrHPV genotype concordance between BD Onclarity HPV Assay and Roche's Linear Array, overall and stratified by hrHPV viral load. We also evaluated the performance of cytology, cytology combined with hrHPV genotyping (Onclarity assay) for HPV16/18 and non-HPV16/18 types, and hrHPV genotyping triage strategies for the detection of cervical intraepithelial neoplasia grade 2 or 3 and worse (CIN2+/CIN3+). Methods: Standard measures (expected agreement, agreement, and κ values) were used to compare Onclarity to the reference test, Linear Array. Twenty-four triage strategies were evaluated by calculating their sensitivities, specificities, and positive and negative predictive values for CIN2+ and CIN3+ detection. Results: Among 734 hrHPV+ samples tested, there was near perfect concordance irrespective of viral load between the Onclarity and Linear Array assays for the individual genotypes [human papillomaviruses (HPV) 16, 18, 31, 45, 51, 52] by Onclarity (κ values ranged from 0.92–0.98). Strategies with adequate specificity (>75%) and the highest sensitivities to detect CIN3+ among 617 women positive for hrHPV, were positivity to HPV16 and/or 31 (Sensitivity: 65.2%, Specificity: 76.9%) and HPV16 and/or 18 (Sensitivity: 58.7%, Specificity: 81.6%). Conclusions: While confirming the importance of HPV16, we found that HPV31 was comparable with HPV18 for the detection of CIN2/3+ in the triage of women positive for hrHPV. Impact: HPV31 may be an important genotype in the triage of women positive for hrHPV.

Background Infections with human papillomaviruses (HPVs) may enter a latent state, and eventually become reactivated following loss of immune control. It is unclear what proportion of incident HPV detections are reactivations of previous latent infections vs new transmissions. Methods The HPV Infection and Transmission among Couples through Heterosexual activity (HITCH) cohort study prospectively followed young newly formed heterosexual partners recruited between 2005 and 2011 in Montréal, Canada. We calculated the fraction of incident HPV detections nonattributable to sexual transmission risk factors with a Bayesian Markov model. Results are the median (2.5th-97.5th percentiles) of the estimated posterior distribution. Results A total of 544 type-specific incident HPV detection events occurred in 849 participants; 33% of incident HPV detections occurred in participants whose HITCH partners were negative for that HPV type and who reported no other sex partners over follow-up. We estimate that 43% (38%–48%) of all incident HPV detections in this population were not attributable to recent sexual transmission and might be potentially reactivation of latent infections. Conclusions A positive HPV test result in many cases may be a reactivated past infection, rather than a new infection from recent sexual behaviors or partner infidelity. The potential for reactivation of latent infections in previously HPV-negative women should be considered in the context of cervical cancer screening.

Background Interplay between vaginal microbiome and human papillomavirus (HPV) remains unclear, partly due to heterogeneity of microbiota. Methods We used data from 546 women enrolled in a cross-sectional study in 5 Brazil. We genotyped vaginal samples for HPV and sequenced V3–V4 region of 16S rRNA gene for vaginal microbiome analysis. We used stepwise logistic regression to construct 2 linear scores to predict high-risk HPV (hrHPV) positivity: one based exclusively on presence of individual bacterial taxa (microbiome-based [MB] score) and the other exclusively on participants’ sociodemographic, behavioral, and clinical (SBC) characteristics. MB score combined coefficients of 30 (of 116) species. SBC score retained 6 of 25 candidate variables. We constructed receiver operating characteristic curves for scores as hrHPV correlates and compared areas under the curve (AUC) and 95% confidence intervals (CI). Results Overall, prevalence of hrHPV was 15.8%, and 26.2% had a Lactobacillus-depleted microbiome. AUCs were 0.8022 (95% CI, .7517–.8527) for MB score and 0.7027 (95% CI, .6419–.7636) for SBC score (P = .0163). Conclusions The proposed MB score is strongly correlated with hrHPV positivity—exceeding the predictive value of behavioral variables—suggesting its potential as an indicator of infection and possible value for clinical risk stratification.

A demonstration project of primary human papillomavirus (HPV) testing was initiated in 2011 among more than 23,000 women attending routine cervical cancer screening. We examined the additional diagnostic performance of HPV genotyping for detecting disease in women with abnormal cytology.Women aged 30 to 65 years were originally screened for HPV using Hybrid Capture II test. Women with positive results were triaged using conventional cytology, and those with atypical squamous cells of undetermined significance or worse (≥ASC-US) were referred to colposcopy. We retrospectively genotyped (Roche cobas 4800 HPV system [Roche Molecular Systems Inc, Pleasanton, CA]) cervical specimens that were HPV + with Hybrid Capture II test and extracted women's medical history postbaseline screening. We calculated positive predictive values (PPVs) and 95% confidence intervals (CIs) of triage tests to detect histologically confirmed cervical intraepithelial neoplasia of grade 2 or worse (CIN2 + ) within the first year of follow-up among women positive for HPV16, HPV18, and HPV16 and/or HPV18 as well as among those negative for HPVs 16 and 18.Of 1,396 HPV-positive women, 1,092 (78%) were classified as normal, 136 (10%) had CIN1, 80 (6%) had CIN2, 81 (6%) had CIN3, and 7 women had cancer throughout the entire follow-up period. Seventy CIN2 + cases were detected within the first year of follow-up. The PPV for detecting CIN2 + was 20.9% (63/239; 95% CI = 16.4-25.9) for ASC-US + cytology. In women with ASC-US + , PPVs were 31.2% (24/77; 95% CI = 21.1-42.7) for HPV16 + , 27.8% (5/18; 95% CI = 9.7-53.5) for HPV18 + , 30.8% (28/91; 95% CI = 21.5-41.3) for HPV16 + and/or HPV18 + women, and 16.6% (35/211; 95% CI = 11.8-22.3) in women testing negative for HPVs 16 and 18.Partial genotyping as an additional triage strategy to cytology can markedly improve clinical diagnostic performance.

We assessed carrageenan's potential to inhibit human papillomavirus (HPV) DNA extraction and amplification in vaginal swab samples collected in a trial, assessing the efficacy of a carrageenan-based gel against HPV infections. Experiment #1 consisted of adding gel (carrageenan-containing or placebo) to swabs and comparing HPV DNA detection by polymerase chain reaction (PCR) to unmanipulated samples collected from the same participants. For Experiments #2 and #3, we tested vaginal samples for inhibition by addition of an internal control and amplification by real-time PCR. Experiment #4 investigated carrageenan's interference with the extraction process by assessing HPV45 detectability in undiluted and diluted HPV45 positive samples (n = 3) with carrageenan versus no gel. In Experiment #1, there was a loss of HPV positivity with the addition of carrageenan (n = 9), but none with placebo gel (n = 5). In Experiments #2 and #3, the absence of the amplified product was observed in samples from the carrageenan arm: 3.3% (1/30) and 0.5% (1/199) of samples. In Experiment #4, HPV45 was not detected in undiluted carrageenan-containing samples, but after 1/50 dilution, the same HPV45 copy number was detected. Carrageenan does not affect the DNA extraction process, and inhibition of HPV DNA amplification by carrageenan occurs infrequently.

Background It is unclear whether sexual transmission rates of human papillomaviruses (HPV) differ between sexes and HPV types. We estimate updated transmission rates from the final HITCH cohort study and propose an estimation method that accounts for interval-censored data and infection clearance. Methods We enrolled young women 18-24 years old and their male sex partners ≥18 years old in Montreal, Canada, between 2005 and 2011. We followed women over 24 months and men over 4 months. We tested genital samples with Linear Array for HPV DNA detection and genotyping. We calculated infection transmission rates between partners using a multistate Markov model via a Bayesian approach. We report the posterior median and 2.5%-97.5% percentile intervals (95% PI). Results We observed 166 type-specific incident HPV transmission events in 447 women and 402 men. The estimated median transmission rate from an HPV-positive to a negative partner was 4.2 (95% PI = 3.1 to 5.3) per 100 person-months. The transmission rate from men-to-women was 3.5 (95% PI = 2.5 to 4.7) and from women-to-men was 5.6 (95% PI = 3.8 to 7.0) per 100 person-months, corresponding to a rate ratio of 1.6 (95% PI = 1.0 to 2.5). Partners reporting always using condoms had a 0.22 (95% PI = 0.05 to 0.61) times lower HPV transmission rate than those reporting never using condoms. HPV16/18 did not have particularly high transmission rates relative to other HPV types. Conclusion Our updated analysis supports previous research suggesting higher women-to-men than men-to-women HPV transmission rates and a protective effect of condoms in heterosexual partnerships. Our results also suggest that crude incidence rates underestimate HPV transmission rates due to interval-censoring. See video abstract at http://links.lww.com/EDE/B794.

Given that high-risk human papillomavirus (HPV) is the necessary cause of virtually all cervical cancer, the clinical meaning of HPV-negative cervical precancer is unknown. We, therefore, conducted a literature search in Ovid MEDLINE, PubMed Central, and Google Scholar to identify English-language studies in which (i) HPV-negative and -positive, histologically confirmed cervical intraepithelial neoplasia grade 2 or more severe diagnoses (CIN2+) were detected and (ii) summarized statistics or deidentified individual data were available to summarize proportions of biomarkers indicating risk of cancer. Nineteen studies including 3,089 (91.0%) HPV-positive and 307 (9.0%) HPV-negative CIN2+ were analyzed. HPV-positive CIN2+ (vs. HPV-negative CIN2+) was more likely to test positive for biomarkers linked to cancer risk: a study diagnosis of CIN3+ (vs. CIN2; 18 studies; 0.56 vs. 0.24; P < 0.001) preceding high-grade squamous intraepithelial lesion cytology (15 studies; 0.54 vs. 0.10; P < 0.001); and high-grade colposcopic impression (13 studies; 0.30 vs. 0.18; P = 0.03). HPV-negative CIN2+ was more likely to test positive for low-risk HPV genotypes than HPV-positive CIN2+ (P < 0.001). HPV-negative CIN2+ appears to have lower cancer risk than HPV-positive CIN2+. Clinical studies of human high-risk HPV testing for screening to prevent cervical cancer may refer samples of HPV test–negative women for disease ascertainment to correct verification bias in the estimates of clinical performance. However, verification bias adjustment of the clinical performance of HPV testing may overcorrect/underestimate its clinical performance to detect truly precancerous abnormalities.

Made available in DSpace on 2020-12-12T02:16:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-08-01 Background Composition of the vaginal microbiome is strongly related to a woman's reproductive health and risk of sexually transmitted infections. Ethnoracial, behavioral, and environmental factors can influence microbiome. The Brazilian population is unique in terms of miscegenation of ethnic groups and behavioral characteristics across different regions. We aimed to characterize the vaginal microbiome of women from 5 geographical regions of Brazil. Methods We sequenced V3-V4 regions of 16S rRNA gene in vaginal samples of 609 reproductive-aged women. We performed logistic regression analyses to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between sociodemographic and behavioral factors with Lactobacillus-depleted microbiome (community state type [CST] IV). Results Vaginal samples were grouped into 5 CST: CST I (L. crispatus predominant, 30.5%), CST II (L. gasseri predominant, 4.4%), CST III (Lactobacillus iners predominant, 36.5%), CST IV (Lactobacillus-depleted, 27.4%), and CST V (L. jensenii predominant, 1.2%). Several factors were independently associated with CST IV, such as smoking (OR, 1.80; 95% CI, 1.02-3.18), number of partners (OR, 2.11; 95% CI, 1.20-3.70), and vaginal douching (OR, 2.24; 95% CI, 1.34-3.74). A protective effect was observed for milk/dairy intake (OR, 0.47; 95% CI, 0.27-0.82) and sitz bathing (OR, 0.43; 95% CI, 0.19-0.98). Conclusions Nearly two thirds of Brazilian women may be at an increased risk for adverse outcomes associated with a vaginal microbiota characterized by the depletion of Lactobacillus or dominance by L. iners, whose protective role has been widely questioned. Several factors related to sexual behavior and intimate hygiene were associated with CST IV. Department of Basic Pathology Federal University of Paraná (UFPR) Department of Pathology Botucatu Medical School Sao Paulo State University (UNESP) Division of Cancer Epidemiology McGill University Institute of Genomic Science University of Maryland School of Medicine Department of Gynecology and Obstetrics Federal University of Paraíba (UFPB) Department of Gynecology and Obstetrics Federal University of Paraná (UFPR) Department of Gynecology and Obstetrics Federal University of Goiás (UFG) Department of Nursing Botucatu Medical School Sao Paulo State University (UNESP) Department of Gynecology and Obstetrics State University of Pará (UEPA) Department of Gynecology and Obstetrics Faculty of Medicine State University of Campinas (UNICAMP) Department of Gynecology and Obstetrics Faculty of Medicine Federal University of Rio Grande Do Norte (UFPR) Department of Pathology Botucatu Medical School Sao Paulo State University (UNESP) Department of Nursing Botucatu Medical School Sao Paulo State University (UNESP)

Background Limited evidence indicates greater female-to-male (F–M) transmission of genital infection with human papillomavirus (HPV) relative to male-to-female (M–F). We verified the hypothesis of a differential transmission rate in couple-based studies by conducting a systematic review and meta-analysis. Methods We searched MEDLINE, EMBASE, Scopus, and Cochrane Library databases for studies published until December 2019. We calculated pooled estimates of F–M and M–F transmission rates and their rate differences per 100 person-months, with 95% confidence intervals (CI), using a random-effects model. We counted occurrences of directionality preponderance for each HPV type. Results We identified 7 eligible studies published between 2008 and 2019, providing data for 752 couples. Pooled estimates for F–M and M–F transmission rates were 3.01 (95% CI, 1.19–7.64; I2 = 97%) and 1.60 (95% CI, 0.86–2.98; I2 = 89%), respectively. The overall rate difference was 0.61 (95% CI, −0.27 to 1.49; I2 = 75%). Three studies provided rates by sex and HPV genotype; 2 favored a preponderance of F–M and 1 favored M–F transmission. Conclusions There was slight evidence for a differential transmission rate favoring higher F–M than M–F transmission with substantial statistical heterogeneity across studies.

Most women positive for human papillomavirus (HPV) are cytology normal. The optimal screen-management of these women is unclear given their risk of developing precancer. We performed a systematic review and meta-analysis of progression rates to precancer and cancer for HPV-positive, cytology normal women. We searched MEDLINE, EMBASE and Scopus for prospective studies measuring the cumulative incidence of precancer and cervical cancer in HPV-positive, cytology/histology normal women. Record screening was performed independently by two reviewers. We modeled the cumulative incidence over time using a multilevel random-effects meta-regression model. We used the model to predict HPV type-specific risks of precancer and cancer over follow-up. Data from 162 unique records were used in our analysis. The average incidence rate of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) in high-risk HPV positive but cytology/histology normal women was 1.0 per 100 women-years (95% CI: 1.0-1.1). This corresponds to an average cumulative risk at 1, 3 and 5 years of 2.1% (95% prediction interval 0.0-9.5), 4.3% (95% prediction interval 0.0-11.5) and 6.4% (95% prediction interval 0.0-13.5). HPV type was a strong predictor of the risk of oncogenic progression. There was substantial heterogeneity in the background precancer risk across studies (P-value < .0001). Our HPV type-specific progression risk estimates can help inform risk-based cervical cancer screening guidelines for HPV-positive women. However, precancer and cervical cancer risks are highly variable and may not be generalizable between populations.

DNA methylation analysis may improve risk stratification in cervical screening. We used a pan-epigenomic approach to identify new methylation markers along the continuum of cervical intraepithelial neoplasia (CIN) to cervical cancer. Physician-collected samples (54 normal, 50 CIN1, 40 CIN2 and 42 CIN3) were randomly selected from women at a single-center colposcopy clinic. Extracted DNA was subjected to Illumina Infinium EPIC array analysis, and methylation was assessed blinded to histopathological and clinical data. CpG sites whose state of methylation correlated with lesion grade were assessed (Spearman correlation), and a weighted methylation score was calculated comparing normal to CIN3. Validation of the top selected genes was performed in an independent cohort (100 normal, 50 CIN1, 50 CIN2, 50 CIN3 and 8 cervical cancers) of new patients, referred for colposcopic examination at three hospitals, using targeted DNA methylation Illumina amplicon sequencing. The relationship between a combined weighted marker score and progression from normal through precancerous lesions and cervical cancer was compared using one-way ANOVA. Our analyses revealed 7,715 CpGs whose methylation level correlated with progression (from normal to CIN1, CIN2 and CIN3), with a significant trend of increased methylation with lesion grade. We shortlisted a bigenic (hyaluronan synthase 1, HAS1 and ATPase phospholipid transporting 10A, ATP10A corresponding to cg03419058 and cg13944175 sites) marker set; r = 0.55, p < 0.0001. Validation of the four most discriminating genes (CA10, DPP10, FMN2 and HAS1) showed a significant correlation between methylation levels and disease progression (p-value < 2.2 × 10-16 , adjusted R2 = 0.952). Translational research of the identified genes to future clinical applications is warranted.

Background: Cervical cancer is the fourth leading cause of death among women worldwide, with 85% of the burden falling on low- to middle- income countries. We studied the correlates of cervical cancer incidence and mortality, and case-fatality in Sub-Saharan Africa. Methods: Country-level data on 16 putative cervical cancer correlates for 37 Sub-Saharan African countries were collected from publicly available data sources. We performed univariate and multiple (stepwise) linear regression analyses to identify correlates of cervical cancer incidence and mortality, and case-fatality. Results: In univariate analyses, incidence and mortality rates were significantly correlated with contraceptive use, penile cancer incidence, and human immunodeficiency virus prevalence. Incidence rates were also correlated with literacy rates, whereas mortality rates were correlated with the proportion of rural population and screening coverage. Multiple regression analyses showed contraceptive use (P = 0.009) and penile cancer incidence (P = 0.004) as associated with cervical cancer incidence. Penile cancer incidence (P = 9.77 × 10–5) and number of medical doctors (P = 0.0433) were associated with mortality. The goodness of fit of the incidence and mortality models was moderate at best, explaining 49% and 37% of variability in the data, respectively. However, the case-fatality model had the best fit explaining most of the variation (adjusted R2 = 0.948; P = 6.822 × 10–16). Conclusions: To reduce the burden of cervical cancer in Sub-Saharan Africa, it would be important to design multimodal interventions that not only target screening and HPV vaccination, but also focus on cervical cancer correlates. Impact: Identifying contextual factors associated with cervical cancer in this region could inform targeted interventions.

Anyplex II HPV-28 (HPV-28) can detect individually 28 HPV genotypes. We assessed the agreement between linear array HPV genotyping (LA-HPV) and HPV-28 for detection of 27 HPV genotypes in 410 stored anogenital samples (75 anal samples, 335 physician-collected cervical samples) collected over 5 years from 410 individuals (13 men, 397 women), including 202 HIV-seropositive individuals. HPV DNA was detected in 393 (95.9%, 95% confidence interval [CI]: 93.4-97.4) and 382 (93.2%, 95% CI: 90.3-95.3) samples with HPV-28 and LA-HPV (p = 0.13), respectively, for a good agreement of 96.3% (κ = 0.65). Of the 10503 HPV typing results, 10195 (780 positive, 9577 negative) were concordant, for an agreement of 97.1% (95% CI: 96.7-97.4) and an excellent of κ = 0.82 (95% CI: 0.80-0.84). The mean type-specific concordance for 27 genotypes was 97.0%, 95% CI: 95.8-98.5 (κ = 0.86 ± 0.07, 95% CI: 0.83-0.88). Excellent agreement was obtained individually for all high-risk genotypes (κ = 0.81-0.97) and for most other genotypes except for types 42, 44, 54, 68, and 69. The mean number of types per sample in discordant samples detected with LA-HPV (3.0, 95% CI: 2.7-3.4) was greater than in concordant samples (1.4, 95% CI: 1.3-1.5; p 0.001). In conclusion, HPV-28 compared favorably with LA-HPV, but was more frequently positive for HPV42 and HPV68.

While launching a campaign to eliminate cervical cancer, the World Health Organization called to halt human papillomavirus (HPV) gender-neutral vaccination (GNV) because of limited vaccine supply, raising ethical and legal questions about female-only vaccination versus GNV. We identified ethical and legal aspects of HPV GNV by searching MEDLINE for records up to February 19, 2021. We also provided an overview of HPV vaccines, the evolution of HPV vaccine recommendations in North America, and a timeline of male HPV vaccination introduction by searching PubMed, Google, and government websites. Four HPV vaccines are available: Cervarix, Gardasil, Gardasil9, and Cecolin. Vaccine recommendations in North America evolved from female only to eventually include males. Following the FDA's approval of the first HPV vaccine for males (2009), 35 countries began vaccinating males (2011–2020). On the basis of 59 eligible records out of 652, we identified the following constructs: lower male awareness of HPV and vaccination (n = 13), limited economic resources (n = 5), shared social responsibility (n = 18), unprotected groups from female-only HPV vaccination (n = 10), limited screening for HPV-associated noncervical cancers (n = 6), consideration of ethical principles (n = 17), and HPV vaccine mandates (n = 5). Ethical and legal aspects must be considered when recommending vaccination for females only or GNV.

Background: Vaccination against human papillomaviruses (HPV) prevents HPV infections and, consequently, cervical lesions. However, the effect of vaccination on HPV transmission within couples is unknown. Methods: We used data from HITCH, a prospective cohort study of heterosexual couples (women ages 18–24 years) in Montreal, 2005 to 2013. Vaccination history was self-reported. Genital samples were tested for HPV DNA by PCR (linear array). Type-specific viral loads were quantified using real-time PCR. OR and HR were estimated using multilevel mixed-effects logistic regression and a parametric model for interval- censored survival-time data, respectively. Differences in viral loads were evaluated using the Friedman ANOVA test. Results: Among 497 couples, 12, 16, and 35 women received 1, 2, or 3 vaccination doses at baseline, respectively. Median age at vaccination was 18 years. Most women (92.1%) had their first coitus before vaccination. At baseline, partner concordance of persistent HPV6/11/16/18 infections was lower in vaccinated than unvaccinated women [adjusted OR = 0.10; 95% confidence interval (CI), 0.01–0.65] but not for non α7/α9/α10-HPV types (adjusted OR = 1.00; 95% CI, 0.44–2.29). Incidence of persistent α7/α9/α10 HPV types in women was inversely associated with vaccination status at baseline (adjusted HR = 0.12; 95% CI, 0.03–0.47). Likewise, male partners of vaccinated women had a lower incidence of α7/α9/α10 HPV infections (adjusted OR = 0.22; 95% CI, 0.05–0.95). Vaccinated women with HPV 6/11/16/18 infections had lower viral loads (P = 0.001) relative to unvaccinated women. Conclusions: Vaccination of sexually active women significantly reduced transmission of α7/α9/α10 HPV types in heterosexual couples. Impact: These results underscore and quantify the positive effect of HPV vaccination on HPV transmission within heterosexual couples.

Background: Self-sampling has become an attractive proposition now that human papillomavirus (HPV) primary testing is being incorporated into cervical cancer screening programs worldwide. We compared predictive values of HPV testing based on self- and physician-collected samples, and cytology, in detecting high-grade cervical intraepithelial neoplasia (CIN). Methods: The Cervical And Self-Sample In Screening (CASSIS) study enrolled 1,217 women ages 16–70 years prior to scheduled colposcopies. Vaginal specimens were self-collected using the validated HerSwab device. Cervical specimens were collected by gynecologists. Specimens were tested for presence of high-risk HPV (hrHPV) by the Cobas 4800 HPV test. We estimated positive predictive values (PPV) and negative predictive values (NPV) and 95% confidence intervals (CI) for a subset of women (n = 700) who underwent cervical biopsy and cytology at the actual CASSIS visit. Results: hrHPV was detected in 329 women (47%) with HerSwab and in 327 (46.7%) with physician sampling. Respective values for HPV16/18 were 119 (17%) and 121 (17.3%). On histology, 134 women had CIN1, 49 had CIN2, 48 had CIN3, 5 had CIN2/CIN3, and 3 had cancers. PPVs for CIN2+ of any hrHPV were 28% (95% CI, 23.2–33.1) and 29.7% (95% CI, 24.8–34.9) for HerSwab and physician samples, respectively. Corresponding values for HPV16/18 were 43.7% (95% CI, 34.6–53.1) and 43.8% (95% CI, 34.8–53.1). PPV of cytology (ASC-US+) was 26.6% (95% CI, 21.6–32.0). Corresponding NPVs (same order as PPVs) were 96.4% (95% CI, 93.9–98.1), 97.8% (95% CI, 95.6–99), 90.9% (95% CI, 88.2–93.1), 91% (95% CI, 88.4–93.2), and 94.7% (95% CI, 91.8–96.8). Conclusions: Our results confirm that HPV self-sampling has comparable performance with a physician-collected sample in detecting cervical lesions. Impact: HPV self-sampling has the potential to increase coverage in cervical cancer screening.

BackgroundWe studied the association between human papillomavirus (HPV) viral load (VL) and HPV concordance.MethodsThe HITCH cohort study included young, heterosexual, recently formed, sexually active couples. Questionnaires and genital samples were collected at 0 and 4 months. Samples were tested for HPV DNA by polymerase chain reaction (PCR; Linear Array). VLs of HPV6/11/16/18/31/42/51 were quantified using type-specific real-time PCR. Correlations between VL and type-specific HPV prevalence and incidence were evaluated using multilevel, mixed-effects linear/logistic regression models.Results We included 492 couples. VLs were higher in penile than vaginal samples. VL at subsequent visits correlated significantly within men (r, 0.373), within women (r, 0.193), and within couples (r range: 0.303–0.328). Men with high VL had more type-specific persistent HPV infections (odds ratio [OR], 4.6 [95% confidence interval {CI}, 2.0–10.5]). High VL in men was associated with prevalent (OR, 5.3 [95% CI, 2.5–11.2]) and incident (OR, 6.7 [95% CI, 1.5–30.7]) type-specific HPV infections in their partner. Women’s VL was associated with type-specific HPV prevalence in their partner at the same (OR, 5.9) and subsequent (OR, 4.7) visit.ConclusionsPersistent HPV infections have limited VL fluctuations. VL between sex partners are correlated and seem predictive of transmission episodes.

More than 7000 incident cancers diagnosed in Canada in 2015 were attributable to infections. The future infection-associated cancer burden can be lowered by reducing the prevalence of major cancer-causing infections; hepatitis B virus (HBV), hepatitis C virus (HCV), Helicobacter pylori (H. pylori) and human papillomavirus (HPV). We modeled the future impact of (1) 10%, 25%, and 50% relative reductions in the prevalence of HBV, HCV and H. pylori and (2) different school-based HPV vaccination coverage levels (lower, current, higher) on Canadian cancer incidence by the year 2042. We modeled counterfactual reductions in HBV, HCV and H. pylori prevalence in 2018, assuming a latency period of 15-years, to estimate the impact on cancer incidence starting in 2033. The number of HPV-attributable cancers among vaccinated cohorts was a function of pre-2018 vaccine coverage levels and the 2018 counterfactuals. A 50% counterfactual reduction in the prevalence of HBV, HCV and H. pylori could prevent an estimated 10,585 cancers from 2018 to 2042; a 25% reduction could prevent 5293 cancers and a 10% reduction could prevent 2117 cancers. Assuming continuity of current estimated country-wide HPV vaccine coverage, 3977 anogenital and 1073 head and neck cancers could be prevented from 2018 to 2042, whereas vaccine coverage of 80% in girls and boys could prevent an additional 311 cancers. Almost 16,000 cancers could be prevented in Canada from 2018 to 2042 with a 50% relative reduction in HBV, HCV and H. pylori prevalence and 80% HPV vaccine coverage of girls and boys.

Summary Background Hand-to-genital contact is hypothesised to be a transmission mode of human papillomavirus (HPV) of the Alphapapillomavirus genus. We compared the relative importance of hand-to-genital and genital-to-genital HPV transmission between sexual partners. Methods In this prospective cohort study, we recruited and followed up female university students aged 18–24 years and their male sexual partners in Montreal, QC, Canada (2005–11). Participants were eligible if they had initiated sexual activity within the past 6 months. Women were examined at clinic visits at baseline and every 4–6 months for up to 24 months. Men had a baseline visit and a single follow-up visit approximately 4 months later. Partners provided hand and genital swab samples, which we tested for DNA of 36 HPV types using PCR. We assessed predictors of incident type-specific HPV detections using Cox proportional hazards models. Findings Participants were recruited between June 5, 2006, and April 4, 2013. 264 women and 291 men had valid hand samples. The hazard ratio (HR) of incident detection of HPV in genital samples from women was 5·0 (95% CI 1·5–16·4) when her partner was positive for the same HPV type on his hand versus negative, but adjustment for his genital HPV status reduced the HR to 0·5 (0·1–1·8). Similarly, the HR of incident detection of HPV on men's genitals was 17·4 (95% CI 7·9–38·5) when his partner was positive for the same HPV type on her hand versus negative, but adjustment for her genital HPV status reduced the HR to 2·3 (0·9–6·2). Conversely, the HR of type-specific incident detection of HPV in genital samples associated with partner genital HPV positivity was 19·3 (95% CI 11·8–31·8) for women and 28·4 (15·4–52·1) for men after adjustment for their hand HPV status. Interpretation Clinicians can reassure their patients that HPV transmission is unlikely to occur through hand-to-genital contact. The majority of genital HPV infections are likely to be caused by genital-to-genital sexual transmission. Funding Canadian Institutes for Health Research, National Institutes of Health, Fonds de la Recherche en Sante du Quebec, and Merck & Co.

Objectives To evaluate the efficacy of a carrageenan-based lubricant gel in reducing the risk of genital human papillomavirus (HPV) infections in women. Methods We conducted a planned interim analysis of a randomized, double-blind, placebo-controlled, phase 2B trial. Women aged 18 years and older were randomly assigned (1:1) to a carrageenan-based gel or a placebo gel to be self-applied every other day for the first month and before and after each intercourse during follow-up. Assessments were performed at 0.5, 1, 3, 6, 9 and 12 months. The primary outcome was incidence of a new infection by an HPV type that was not present at baseline. Intention-to-treat analyses were performed. Results Between January 2013 and June 2017, a total of 280 participants were randomly assigned to the carrageenan (n = 141) or the placebo (n = 139) arm. All participants were included in safety analyses, but three (1%) were excluded from efficacy analyses (HPV results unavailable for two participants in the carrageenan and one participant in the placebo arm). The median follow-up time was 9.2 months (interquartile range, 1.9–13.2 months). A total of 59 (42%) of 139 participants in the carrageenan arm and 78 (57%) of 138 participants in the placebo arm became infected by at least one new HPV type (hazard ratio = 0.64, 95% confidence interval = 0.45–0.89, p 0.009). A total of 62 (44%) of 141 participants in the carrageenan arm versus 43 (31%) of 139 participants in the placebo arm reported an adverse event (p 0.02), none of which was deemed related to the gels. Conclusions Our trial's interim analysis suggests that using a carrageenan-based lubricant gel can reduce the risk of genital HPV infections in women.

Carrageenan, an extract from red algae, was identified over a decade ago as a potent inhibitor of human papillomavirus (HPV) infection in vitro. After this discovery, several studies evaluated carrageenan's anti-HPV activity in cells, experimental animals, and humans. We reviewed the evidence for carrageenan's anti-HPV activity. Studies had to be in vitro, in vivo, or in humans and report on carrageenan's anti-HPV activity. Of the 39 records identified in PubMed and 29 records in Clinicaltrials.gov, 22 records were included after screening: 8 in vitro (including 2 ex vivo), 3 in vivo, 5 in vitro and in vivo, 3 clinical studies, and 3 trial protocols. A total of 12 studies evaluated carrageenan exclusively, whereas 7 considered carrageenan combined with additional antiviral or other agents. One study protocol will evaluate carrageenan exclusively, and 2 others will evaluate carrageenan-combination products. Most clinical studies evaluated carrageenan's ability to prevent HPV acquisition (n = 4), whereas one study explored its ability to promote clearance of existing infection (defined as the absence of HPV DNA detection). Carrageenan's anti-HPV activity was observed consistently across study designs, except in 2 studies: 1 in vitro study where 2 of the HPV types tested were not significantly inhibited by carrageenan and 1 phase IIB trial in gay, bisexual, and other men who have sex with men. This review supports the premise that carrageenan, alone or in combination with other antiviral agents, might be a potential prevention strategy complementary to HPV vaccination for women.

Background We assessed the association between serum 25-hydroxyvitamin D levels and genital human papillomavirus (HPV) prevalence, incidence, and clearance among female participants of the HITCH cohort study. Methods We genotyped HPV DNA in vaginal samples and quantified baseline serum 25-hydroxyvitamin D levels using Roche’s Linear Array and Total vitamin D assay, respectively. We used logistic and Cox proportional hazards models to respectively estimate adjusted odds ratios (OR) and hazards ratios (HR) with 95% confidence intervals (CI). Results There was no association between vitamin D levels (every 10ng/mL increase) at baseline and HPV prevalence (OR=0.88, CI:0.73-1.03) or incidence (HR=0.88, CI:0.73-1.06), but we observed a modest negative association with HPV clearance (HR=0.76, CI:0.60-0.96). Vitamin D levels Conclusion This study provided no evidence of an association between low vitamin D levels and increased HPV prevalence, acquisition, or clearance.

We compared clinical performance of p16/Ki-67 dual-stained cytology and human papillomavirus (HPV) genotyping, via different algorithms-alone, or in combination with cytology-to identify cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+) in women referred to as colposcopy. We included 492 cervical specimens (134 normal, 130 CIN1, 99 CIN2, 121 CIN3, 8 cancers) randomly selected from 1158 specimens with valid conventional cytology, HPV (cobas 4800 HPV test) and biopsy results. Dual-stained cytology was retrospectively performed (CINtec PLUS assay) on PreservCyt material; slides were read by a cytologist and confirmed by two pathologists, blinded to cytology, biopsy and genotyping results. Sensitivity and specificity (95% confidence intervals in parentheses) of dual-stained cytology to detect CIN2+ and CIN3+ were compared to other screening tests available for the same women. Positivity rate for dual-stained cytology increased with histological severity: 30.6% in normal, 41.5% in CIN1, 72.7% in CIN2, 86.8% in CIN3 and 87.5% in cancer. Dual-stained cytology alone had lower sensitivity than HPV testing for CIN2+ [80.7% (75.0-85.6) vs 89.9% (85.3-93.5)] and CIN3+ [86.8% (79.7-92.1) vs 92.3% (86.2-96.2)]. However, corresponding specificity values were higher [64.0% (57.9-69.8) vs 56.1% (49.8-62.1) for CIN2+; 54.0% (48.7-59.2) vs 44.4% (39.2-49.6) for CIN3+]. Combining dual-stained cytology with an ASC-US abnormality threshold decreased specificity to 31.4% (25.9-37.4) for CIN2+ and 24.2% (19.9-29.0) for CIN3+. The corresponding values considering low squamous intraepithelial lesion threshold values were 42.8% (36.8-49.0) and 35.0% (30.1-40.1). Dual-stained cytology and HPV testing exhibited similar performance, although the former improved the specificity by 7.9% and 9.6% for CIN2+ and CIN3+, respectively.

Objective We compared the self-sampling performance of the newly designed HerSwab™ device with a physician-collected cervical sample and another self-sample using the cobas® PCR Female swab for the detection of cervical intraepithelial neoplasia (CIN) and cancer. Methods Women referred for colposcopy at McGill University affiliated hospital clinics collected two consecutive self-samples, one with HerSwab™ and one with cobas® swab, after receiving instructions. The order of sampling was randomized. The colposcopist then collected a cervical sample and conducted a colposcopic examination. Samples were tested for human papillomavirus (HPV) DNA. Sensitivity and specificity to detect CIN2+ and respective 95% confidence intervals (CI) were calculated to compare sampling approaches. The HPV testing agreement between samples was measured using the Kappa statistic. Results Of 1217 women enrolled, 1076 had complete results for HPV and cytology; 148 (13.8%) had CIN1, 147 (13.7%) had CIN2/3, and 5 (0.5%) had cancer. There was very good agreement between methods for HPV detection (HerSwab™ versus physician: kappa=0.84; cobas® swabs versus physician: kappa=0.81; HerSwab™ versus cobas® swabs: kappa=0.87). The sensitivity of HPV detection for CIN2+ was 87.6% (95%CI: 79.8–93.2) with self-sampling using HerSwab™, 88.6% (95%CI: 80.9–94.0) with self-sampling using the cobas® swab, and 92.4% (95%CI: 85.5–96.7) with physician sampling. Corresponding estimates of specificity were 58.1% (95%CI: 54.1–62.1), 55.0% (95%CI: 50.9–59.0) and 58.7% (95%CI: 54.6–62.6). Cytology (ASC-US or more severe) done on the physician-collected specimen was 80.2% (95%CI: 70.8–87.6) sensitive and 61.4% (95%CI: 57.2–65.5) specific for CIN2+. Conclusions The HerSwab™ had good agreement with physician sampling in detecting HPV, and adequate performance in detecting high-grade lesions among women referred to colposcopy for abnormal cytology.

Human papillomavirus (HPV) infection, a common sexually transmitted infection, is causally associated with cervical cancer. Vaccination against HPV provides protection; however, HPV vaccines are exclusively prophylactic. Carrageenan, an extract from red algae, demonstrated potent anti-HPV activity in in vitro and animal studies. We describe the protocol for the Carrageenan-gel Against Transmission of Cervical Human papillomavirus (CATCH) study, an ongoing randomized controlled trial among sexually active young females, aimed at evaluating the efficacy of a carrageenan-based gel in reducing type-specific incidence (i.e. new detections of HPV) and prevalence (i.e. absence of a previously detected HPV) of genital HPV infections as well as participant adherence to the intervention. The CATCH study is a phase IIB double-blind randomized placebo-controlled trial. Eligible women 18 years and older are randomized 1:1 to the carrageenan-containing gel or placebo gel arm. For the first month, participants use the study gel intra-vaginally every other day, and over the 12-month study period, prior to and after each act of vaginal intercourse. At each study visit (months 0, 0.5, 1, 3, 6, 9, 12), participants provide a self-collected vaginal sample and record information on sexual activities, adherence, and adverse events using a computerized questionnaire. The primary outcomes are incident and prevalent type-specific cervicovaginal HPV infection. The primary analyses are based on intention-to-treat whereas per-protocol analyses are conducted based on measures of adherence. Trial registration: ISRCTN96104919.

In the province of Québec, Canada, the Bacillus Calmette-Guérin (BCG) vaccine was offered to newborns and school-age children from the 1950s to mid-1970s in an organized tuberculosis prevention program.We aimed to describe the annual rates of skin test administration, proportion of skin tests that were positive, and rates of BCG vaccination from 1956 to 1974 according to age, sex, and administrative region.For rates, numerators were extracted from the Québec BCG Vaccination Registry whereas population denominators were obtained from the Canadian Census and governmental publications. Time trends were assessed with linear regression.A total of 2,755,336 skin tests and 2,531,366 BCG vaccinations were administered. Yearly rates of skin tests, routinely administered before vaccination among all except newborns, were highest among children aged 5-9 (9.3 per 100) and 10-14years (7.9 per 100). The proportion of positive skin tests varied greatly by age, ranging from 10.2% among children1year to 67.2% among adults ≥20years. The vast majority of individuals who had a negative skin test were subsequently vaccinated, whereas those with a positive result were not, as per recommended guidelines. The average annual vaccination rate was highest among children aged1year (43.8 per 100) and 5-9year-olds (6.9 per 100). There were salient differences in immunization rates, including positive skin tests and vaccinations, across administrative regions but no difference by sex.This is the first comprehensive description of the tuberculosis prevention program in Québec which offered free, non-mandatory BCG vaccination. Our results confirm that the targeted groups, newborns and school-age children, were preferentially reached. Socioeconomic, demographic, and organizational factors may explain regional differences in immunization rates. Beyond presenting a historical context for this vaccination campaign, our findings are relevant to contemporary uses of the Québec BCG Vaccination Registry in epidemiological research.

Background: Alpha-human papillomavirus (α-HPV) plays a causal role in cervical cancer, but little is known about the epidemiology of genital Beta-human papillomavirus (β-HPV) infection. Methods: We used Luminex and PCR hybridization to detect β- and α-HPVs prevalence at enrollment and 12-month follow-up in cervical samples from 505 women enrolled in the Ludwig-McGill cohort study. We compared epidemiologic correlates of both β- and α-HPVs and compared genotypes between these genera with respect to co-occurrence and association with cervical cytologic abnormalities. Results: Infection with β-HPV types was more prevalent than that with α-HPV types at both visits (cumulative prevalences: 27.3% vs. 21.6%, respectively, P = 0.034). β-HPVs were mostly transient; however, only 1.98% women retained their original positivity at 12 months, whereas persistence was higher for α-HPVs (5.15%; P = 0.007). Age, parity, and sexual activity variables were predictors of α-HPV but not of β-HPV. α- and β-HPV types occurred independently. Increased risk of cervical abnormalities was restricted to women infected with α-9 or α-6 HPV types. We found no epidemiologic correlates for β-HPV infections. Conclusions: Detection of β-HPV types in the cervix tends to occur as random and transient episodes not explained via the sexual-transmission correlates that characterize infections by α-HPVs. Impact: Although it is plausible that β-HPVs may play a direct or indirect carcinogenic role, the lack of epidemiologic correlates for detection episodes of these viruses and lack of association with cervical lesions speak against their ancillary role as sexually transmitted agents in cervical carcinogenesis. Cancer Epidemiol Biomarkers Prev; 26(8); 1312–20. ©2017 AACR.

Background Assortative sexual mixing, the tendency for individuals to choose partners with similar characteristics to themselves, may be an important contributor to the unequal distribution of sexually transmitted infections in populations. We analyzed the tendency for assortative mixing on demographic and sexual behaviors characteristics in newly formed young adults dating partnerships. Methods Women aged 18 to 24 years and their male sexual partners of no more than 6 months were recruited during 2005 to 2010 at universities in Montreal, Canada. New dating partners were also prospectively recruited during the 2-year follow-up. We used Spearman and Newman coefficients to examine correlations between partners' demographic characteristics and sexual behaviors, and multivariable logistic modeling to determine which characteristics were assortative. Results Participants in 502 recruited partnerships were assortative on age (Spearman P = 0.60), smoking behavior (P = 0.43), ethnicity (Newman coefficient=0.39), lifetime number of sexual partners (P = 0.36), sex partner acquisition rates (P = 0.22), gap length between partnerships (P = 0.20), and on whether they had concurrent partners (P = 0.33). Partners were assortative on number of lifetime partners, sexual partner acquisition rates, concurrency, and gap length between partnerships even after adjustment for demographic characteristics. Reported condom use was correlated between initial and subsequently recruited partners (P = 0.35). There was little correlation between the frequencies of vaginal/oral/digital/anal sex between subsequent partnerships. Conclusions Dating partnerships were substantially assortative on various sexual behaviors as well as demographic characteristics. Though not a representative population sample, our recruitment of relatively new partnerships reduces survivor bias inherent to cross-sectional surveys where stable long-term partnerships are more likely to be sampled.

Lifetime number of sex partners, marital status, and history of sexually transmitted disease were associated with human papillomavirus (HPV) acquisition among women without prior exposure to HPV infection, with no observed differences in risk determinants patterns for HPV infections by length of follow-up. Supplemental digital content is available in the text., Background Global variation in human papillomavirus (HPV) prevalence and persistence may be explained by differences in risk factors, such as sexual activity, oral contraceptive use, and behavioral factors. We evaluated determinants of acquisition and clearance of HPV infection among young women previously unexposed to HPV. Methods Five hundred thirty-four women aged 15 to 25 years who were cytology and HPV DNA negative, and seronegative for anti-HPV-16/18 antibodies, were recruited (July 2000–September 2001) from study centers in Brazil, the United States, and Canada (NCT00689741/NCT00120848). They were followed up for 76 months. Cervical samples were HPV genotyped via polymerase chain reaction. We used multivariable (forward stepwise, P = 0.15) Cox proportional hazards regression to estimate rate ratios (RR) and 95% confidence intervals (CI), separately according to length of follow-up time. Results On short-term follow-up (0–27 months), 257 (48%; 8535.80 person-months; incidence rate = 30.11; 95% CI, 26.64–34.02) incident HPV infections were detected. Marital status, lifetime number of sex partners, history of any sexually transmitted disease, and occasional use of oral contraceptives were strongly associated with acquisition of any HPV. Having 2 or more lifetime sex partners (RR, 2.03; 95% CI, 1.37–3.02) and a history of any sexually transmitted disease (RR, 1.98; 95% CI, 1.19–3.29) were the most important determinants of high-risk HPV (hrHPV) incidence. During the entire follow-up (0–76 months), an increased hrHPV clearance was found among women in North America (RR, 1.38; 95% CI, 1.08–1.78) and black women (RR, 1.64; 95% CI, 1.04–2.60). Greater number of lifetime partners was associated with reduced clearance rates for any HPV (RR, 0.65; 95% CI, 0.43–0.98). Conclusions We identified variation in risk of HPV acquisition and clearance among women unexposed to HPV at baseline.

Background: Human papillomavirus (HPV) types 6 and 11 are mainly associated with the development of genital warts and recurrent respiratory papillomatosis. We examined intratypic genetic variability of both viral types with the development of cervical cytologic abnormalities in Brazilian women. Methods: We used PCR sequencing to characterize variants of HPVs 6 and/or 11 in cervical swabs from women in the Ludwig–McGill Cohort Study. We used a binomial generalized estimating equations (GEE) model with logit link to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations between HPV 6 and 11 variants and cytologic abnormalities. Results: B1 and B3 HPV6 and A2 HPV11 variants were the most common isolates identified. Compared with HPV6-negative women, the ORs among women harboring HPV6 B1 or B3 variants were 6.3 (95% CI, 2.3–17.0) and 2.3 (95% CI, 0.6–9.7) for atypical cells of undetermined significance (ASCUS)/low squamous intraepithelial lesions (LSIL), respectively, and 1.7 (95% CI, 0.6–5.1) and 1.2 (95% CI, 0.3–4.7) for ASCUS/LSIL/high squamous intraepithelial lesions (HSIL). Respective ORs were 5.0 (95% CI, 1.7–14.6) and 2.8 (95% CI, 1.0–8.1) upon comparing women with HPV11 A2 variants to HPV11-negative women. All associations disappeared when adjusting for coinfections with high-risk HPV types. Conclusions: Our data do not support an association between low-risk HPVs 6 and 11 genetic variability and cervical abnormalities. Impact: Risk of cervical cytologic abnormalities is not affected by intratypic polymorphism in HPVs 6 and 11.

International audience

Background Visual inspection with acetic acid (VIA) and Lugol’s iodine (VILI) are used to screen women for cervical cancer in low-resource settings. Little is known about correlates of their diagnostic accuracy by healthcare provider. We examined determinants of VIA and VILI screening accuracy by examiner in a cross-sectional screening study of 1528 women aged 30 years or older in a suburb of Kinshasa, Democratic Republic of Congo. Methods We used a logistic regression model for sensitivity and specificity to estimate the diagnostic accuracy of VIA and VILI, independently performed by nurse and physician, as a function of sociodemographic and reproductive health characteristics. Results Nurses rated tests as positive more often than physicians (36.3% vs 30.2% for VIA, 26.2% vs 25.2% for VILI). Women’s age was the most important determinant of performance. It was inversely associated with sensitivity (nurse’s VIA: p

International audience; BACKGROUND: Results have been conflicting as to whether Bacillus Calmette-Guérin (BCG) vaccine, a non-specific stimulator of the immune function, protects, predisposes or is unrelated to the development of childhood asthma. In this systematic review and meta-analysis, we qualitatively and quantitatively appraised the epidemiological evidence. METHODS: Eligible studies were identified using a search strategy that included a computerized literature search and a manual search of each article's reference list, up to June 2008. A total of 23 studies were included (10 cohort, 5 case-control and 8 cross-sectional). Each study was summarized and rated for methodological quality. Pooled odds ratio (OR) estimates and 95% confidence intervals (CIs) were calculated using fixed-effects (FE) or random-effects (RE) models; if heterogeneity was present, the latter was used. Three indicators of BCG exposure were considered including BCG vaccination, tuberculin response and scar diameter. RESULTS: The pooled estimate of association for 23 studies reporting on any of the three indicators suggested a protective effect of BCG exposure on childhood asthma occurrence. The studies were heterogeneous, especially when tuberculin response was considered. Restriction to a subgroup of 16 studies that considered BCG vaccination indicated a protective effect with no evidence of heterogeneity. The overall pooled OR using an FE model was 0.86 (95% CI 0.79-0.93). Exclusion of three studies with the lowest quality scores showed a similar association. CONCLUSION: These results strengthen the epidemiological evidence in support of the hypothesis that exposure to the BCG vaccine in early life prevents asthma, possibly through a modulation of the immune maturation process.

Cervical cancer control includes primary prevention through vaccination to prevent human papillomavirus (HPV) infection and secondary prevention through screening to detect and treat cervical precancerous lesions. This review summarizes the evidence for the population impact of vaccines against oncogenic HPV types in reducing the prevalence of cervical precancerous lesions. We examine the gradual shift in screening technology from cervical cytology alone to cytology and HPV cotesting, and finally to the recognition that HPV testing can serve alone as the new screening paradigm, particularly in the initial post-vaccination era. We should expect an impact on screening performance and practices, as cohorts of HPV-vaccinated girls and adolescents reach cervical cancer screening age. In preparation for changes in the screening paradigm for the vaccination era, we propose that policymaking on cervical cancer screening should mirror current practices with other cancers as benchmarks. Cervical precancerous lesions will become a very rare condition following the widespread implementation of HPV vaccines with broader coverage in the number of preventable oncogenic types. Irrespective of screening technology, the false positive results will far outnumber the true positive ones, a tipping point that will herald a new period when the harms from cervical cancer screening will outweigh its benefits. We present a conceptual framework to guide decision making when we reach this point within 25-30 years.

Cervical cancer (CC) morbidity and mortality have decreased in the United States, but they remain high among black women. We assessed racial disparities in CC mortality, accounting for socioeconomic status (SES). We linked data from the 1988 to 2007 Surveillance Epidemiology and End Results (SEER) database to the US Census. Additional SES information was obtained through linkage with Area Resource Files. We used the Kaplan-Meier method for estimating probabilities following CC diagnosis and Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CC mortality by race. The models were incrementally adjusted for marital status, registry, period, stage, age at diagnosis, histology, treatment, household income, poverty and unemployment rates. We stratified the analyses by disease stage and American state. A total of 44,554 women with CC were identified. Compared to white women, black women had a higher risk of dying from CC; crude and adjusted HRs were 1.41 (CI: 1.34-1.48) and 1.09 (CI: 1.03-1.15), respectively. Corresponding estimates for Hispanic women were 0.85 (CI: 0.80-0.89) and 0.75 (CI: 0.71-0.80). Black women diagnosed at late disease stages had a higher risk of CC death, whereas Hispanic women diagnosed at early and late stages had significantly lower risks. Black CC patients in California experienced poorer survival relative to white women. Conversely, longer CC survival was seen among Hispanic women in California, Georgia and Utah. While crude estimates indicated an increased CC death risk among black women, risks diminished upon adjustment for clinical and sociodemographic characteristics.

BACKGROUND: When using administrative databases for epidemiologic research, a subsample of subjects can be interviewed, eliciting information on undocumented confounders. This article presents a thorough investigation of the validity of a two-stage sample encompassing an assessment of nonparticipation and quantification of the extent of bias. METHODS: Established through record linkage of administrative databases, the Quebec Birth Cohort on Immunity and Health (n=81,496)aims to study the association between Bacillus Calmette-Guerin (BCG) vaccination and asthma. Among 76,623 subjects classified in 4 BCG-asthma strata, a two-stage sampling strategy with a balanced design was used to randomly select individuals for interviews. We compared stratum-specific socio demographic characteristics and healthcare utilization of Stage 2 participants (n=1643) with those of eligible nonparticipants (n=74,980) and non respondents (n=3157). We used logistic regression to determine whether participation varied across strata according to these characteristics. The effect of nonparticipation was described by the relative odds ratio (ROR=ORparticipants/ORsource population) for the association between socio demographic characteristics and asthma. RESULTS: Parental age at childbirth, area of residence, family income, and healthcare utilization were comparable between groups. Participants were slightly more likely to be women and have a mother born in Quebec. Participation did not vary across strata by sex, parental birthplace, or material and social deprivation. Estimates were not biased by nonparticipation; most RORs were below one and bias never exceeded 20%. CONCLUSIONS: Our analyses evaluate and provide a detailed demonstration ofthe validity of a two-stage sample for researchers assembling similar research infrastructures.

International audience; Human papillomaviruses (HPV) are associated with head and neck cancers (H&NC). Transmission of HPV to the upper aerodigestive tract occurs plausibly through sexual contact, although epidemiologic evidence on the role of sexual behaviours in H&NC aetiology is inconsistent. We conducted a meta-analysis of studies examining the association between four indicators of sexual behaviours (number of sexual partners and oral sex partners, oral sex practice, and age at first intercourse) and H&NC. Summary odds ratios (OR) and 95% confidence intervals (CI) were estimated using fixed and random effects models for each indicator, contrasting 'highest' to 'lowest', 'ever' to 'never', or 'youngest' to 'oldest' categories. Twenty case-control studies were included out of 3838 identified publications. Using random effects models, summary ORs suggested an increased risk of H&NC for number of sexual partners [OR=1.29, 95% CI: 1.02-1.63] (19 studies) and number of oral sex partners [OR=1.69, 95% CI: 1.00-2.84] (5 studies), whereas no effect was observed with oral sex practice [OR=1.09, 95% CI: 0.88-1.35] (17 studies) and age at first intercourse [OR=1.40, 95% CI: 0.71-2.79] (6 studies). For number of sexual partners and oral sex practice, which were assessed in more studies, we further excluded studies contributing to heterogeneity and those not adjusted for age, sex, smoking, and alcohol consumption. The summary ORs were 0.95 (95% CI: 0.75-1.20) for number of sexual partners and 1.03 (95% CI: 0.84-1.26) for oral sex practice. Our findings highlight that observed associations might be partly attributed to confounding effects of sociodemographic and behavioural factors.

Knowledge of cervical human papillomavirus (HPV) status might influence a cytotechnician's assessment of cellular abnormalities. The authors compared original cytotechnicians' Papanicolaou (Pap) readings for which HPV status was concealed with Pap rereads for which HPV status was revealed separately for 3 screening populations.Previously collected cervical Pap smears and clinical data were obtained from the Canadian Cervical Cancer Screening Trial (study A), the Democratic Republic of Congo Community-Based Screening Study (study B), and the Brazilian Investigation into Nutrition and Cervical Cancer Prevention (study C). Smears were reread with knowledge of HPV status for all HPV-positive women as well as a sample of HPV-negative women. Diagnostic performance of Pap cytology was compared between original readings and rereads.A total of 1767 Pap tests were reread. Among 915 rereads for HPV-positive women, the contrast between "revealed" and "concealed" Pap readings demonstrated revisions from negative to positive results for 109 women (cutoff was atypical squamous cells of undetermined significance or worse) and 124 women (cutoff was low-grade squamous intraepithelial lesions [LSIL] or worse). For a disease threshold of cervical intraepithelial neoplasia of grade 2 or worse, specificity significantly declined at the atypical squamous cells of undetermined significance cutoff for studies A (86.6% to 75.3%) and C (42.5% to 15.5%), and at the LSIL cutoff for study C (61.9% to 37.6%). Sensitivity remained nearly unchanged between readings, except in study C, in which reread performance was superior (91.3% vs 71.9% for the LSIL cutoff).A reduction in the diagnostic accuracy of Pap cytology was observed when revealing patients' cervical HPV status, possibly due to a heightened awareness of potential abnormalities, which led to more false-positive results.

The majority of cross-sectional studies have shown a higher prevalence of ventilatory impairment in welders while only few longitudinal studies were able to detect chronic effects on spirometry or bronchial responsiveness. The aim of the study was to determine the incidence of probable occupational asthma (OA), bronchial obstruction and hyperresponsiveness among 286 students entering an apprenticeship programme in the welding profession. This epidemiological prospective cohort study consisted of a baseline assessment survey and two follow-up assessments. A respiratory symptom questionnaire was administered at each visit. Spirometry and methacholine bronchial challenge test results, conducted once prior to onset of exposure and later after an average of 15 months of apprenticeship, were available for 194 subjects. The incidence of probable OA was approximately 3% (6 of 194). The incidence of bronchial hyperresponsiveness, defined as a > or = 3.2-fold decrease in the provocative concentration causing a 20% fall in the forced expiratory volume in one second from baseline to the end of the study was 11.9%. A statistically significant difference was found between the baseline and end of study for the lung function values. In particular, the forced expiratory volume per cent predicted had significantly dropped by 8.4% on average. The significance of these early pulmonary function changes in relation to possible chronic effects of exposure to welding fumes and gases remains to be explored.

International audience; BACKGROUND:The exact nature and direction of the association between a history of allergic diseases and lung cancer risk remain controversial.OBJECTIVE:To examine the association between self-reported history of allergic diseases and lung cancer using data from a population-based case-control study conducted in the Montreal metropolitan area (1996-2002).METHODS:The study is based on interview data collected from 1,169 incident lung cancer cases and 1,486 controls. Separate logistic regression models were used to estimate the relative risk of lung cancer, using odds ratios (ORs) and 95% confidence intervals (CIs), in subjects with vs without asthma, eczema, or hay fever after adjustment for several sociodemographic and lifestyle factors, including smoking.RESULTS:For asthma, the OR was 0.90 (95% CI 0.65-1.24), which decreased to 0.76 (95% CI 0.54-1.08) for subjects whose onset was more than 2 years before lung cancer diagnosis or interview and then to 0.64 (95% CI 0.44-0.93) when restricted to subjects who reported using medication for their asthma. For eczema, the point estimate was 0.73 (95% CI 0.48-1.12), which decreased to 0.63 (95% CI 0.38-1.07) when considering eczema only in those who reported medication use. Hay fever showed the strongest inverse association with lung cancer (OR 0.37, 95% CI 0.24-0.59).CONCLUSION:All 3 allergic diseases examined were inversely associated with lung cancer, although the strength of the protective effect varied. History of allergic diseases seems to have a protective role in lung cancer incidence, after consideration of potential confounders, including lifetime smoking history.

The etiology of childhood cancers remains generally unknown. Given that the metabolites of alcohol are likely carcinogens and that leukemia, the most frequent childhood cancer, can arise in utero, the study of alcohol consumption as a potential risk factor for the development of childhood cancer is justified. This article summarizes the epidemiological evidence on the association between parental exposure to alcohol and the risk of childhood cancers. To do this, a thorough search of the literature from 1960 to 2003 using the PubMed database was carried out. It yielded 33 case-control studies published between 1982 and 2003, including 13 studies that considered paternal exposure in the preconceptional period. In 10 of the 33 studies at least 1 statistically significant risk increase was reported in relation with parental alcohol consumption; in 7 of these studies the increase was related to maternal consumption, whereas in 3 studies, it was related to paternal consumption. The cancers most often found associated with parental drinking were leukemia, brain tumors, and neuroblastoma. A few studies also reported a protective effect with maternal exposure at modest levels. Inconsistencies in the results and the low risks reported do not suggest an association between childhood cancer and parental consumption of alcohol. However, before reaching any definitive conclusions, methodological issues need to be addressed in future studies, as well as the role of genetic susceptibility. Moreover, subtypes of specific cancers need to be studied separately.

Background There are inconsistencies in the literature on reproductive and genital health determinants of human papillomavirus (HPV) infection, the primary cause of cervical cancer. We examined these factors in the Ludwig-McGill Cohort Study, a longitudinal, repeated-measurements investigation on the natural history of HPV infection. Methods We analyzed a cohort subset of 1867 women with one complete year of follow-up. We calculated odds ratios (OR) and 95 % confidence intervals (CI) for reproductive and genital health characteristics from questionnaire and laboratory data in relation to 1-year period prevalence of HPV infection. Two outcomes were measured; the first based on phylogenetic grouping of HPV types based on tissue tropism and oncogenicity (Alphapapillomavirus Subgenus 1: species 1, 8, 10 and 13; Subgenus 2: species 5, 6, 7, 9, 11; Subgenus 3: species 3, 4 and 14) and the second based on transient or persistent HPV infections. Results Lifetime (Subgenus 3 OR = 2.00, CI: 1.23–3.24) and current (Subgenus 3 OR = 2.00, CI: 1.15–3.47) condom use and use of contraceptive injections (Subgenus 1 OR = 1.96, CI: 1.22–3.16, Subgenus 2 OR = 1.34, CI: 1.00–1.79) were associated with increased risk of HPV infection. Intrauterine device use was protective (Subgenus 1 OR = 0.48, CI: 0.30–0.75, Subgenus 2 OR = 0.78, CI: 0.62–0.98). These factors were not associated with persistence of HPV infection. Tampon use, previous gynecologic infections and cervical inflammation were associated with an overall increased risk of HPV infection. Conclusions Cervical HPV infection was associated with reproductive and genital health factors. Further studies are necessary to confirm the low to moderate associations observed. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1446-x) contains supplementary material, which is available to authorized users.