A 16-month-long experience of COVID-19 in allogeneic haematopoietic stem cell transplantation recipients: An SFGM-TC multicentre cohort study.

This 16-month-long multicentre retrospective study of 225 allogeneic haematopoietic stem cell transplantation (alloHSCT) recipients with COVID-19 examines risk factors for severity and mortality, describing the successive waves of infections (from March to June 2020 and from August 2020 to June 2021). We confirm the negative role of low respiratory tract disease and immunosuppressive treatment. We highlight significantly lower percentages of severe forms and COVID-19-related mortality during the second wave. Monthly comparative evolution of cases in alloHSCT recipients and in the French population shows a higher number of cases in alloHSCT recipients during the first wave and a decrease from February 2021.

Statin Use and Incidence of Parkinson's Disease in Women from the French E3N Cohort Study.

BACKGROUND: Statins represent candidates for drug repurposing in Parkinson's disease (PD). Few studies examined the role of reverse causation, statin subgroups, and dose-response relations based on time-varying exposures. OBJECTIVES: We examined whether statin use is associated with PD incidence while attempting to overcome the limitations described previously, especially reverse causation. METHOD: We used data from the E3N cohort study of French women (follow-up, 2004-2018). Incident PD was ascertained using multiple sources and validated by experts. New statin users were identified through linked drug claims. We set up a nested case-control study to describe trajectories of statin prescriptions and medical consultations before diagnosis. We used time-varying multivariable Cox proportional hazards regression models to examine the statins-PD association. Exposure indexes included ever use, cumulative duration/dose, and mean daily dose and were lagged by 5 years to address reverse causation. RESULTS: The case-control study (693 cases, 13,784 controls) showed differences in case-control trajectories, with changes in the 5 years before diagnosis in cases. Of 73,925 women (aged 54-79 years), 524 developed PD and 11,552 started using statins in lagged analyses. Ever use of any statin was not associated with PD (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.67-1.11). Alternatively, ever use of lipophilic statins was significantly associated with lower PD incidence (HR = 0.70, 95% CI = 0.51-0.98), with a dose-response relation for the mean daily dose (P-linear trend = 0.02). There was no association for hydrophilic statins. CONCLUSION: Use of lipophilic statins at least 5 years earlier was associated with reduced PD incidence in women, with a dose-response relation for the mean daily dose. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Ability of epidemiological studies to monitor HPV post-vaccination dynamics: a simulation study.

Genital human papillomavirus (HPV) infections are caused by a broad diversity of genotypes. As available vaccines target a subgroup of these genotypes, monitoring transmission dynamics of nonvaccine genotypes is essential. After reviewing the epidemiological literature on study designs aiming to monitor those dynamics, we evaluated their abilities to detect HPV-prevalence changes following vaccine introduction. We developed an agent-based model to simulate HPV transmission in a heterosexual population under various scenarios of vaccine coverage and genotypic interaction, and reproduced two study designs: post-vs.-prevaccine and vaccinated-vs.-unvaccinated comparisons. We calculated the total sample size required to detect statistically significant prevalence differences at the 5% significance level and 80% power. Although a decrease in vaccine-genotype prevalence was detectable as early as 1 year after vaccine introduction, simulations indicated that the indirect impact on nonvaccine-genotype prevalence (a decrease under synergistic interaction or an increase under competitive interaction) would only be measurable after >10 years whatever the vaccine coverage. Sample sizes required for nonvaccine genotypes were >5 times greater than for vaccine genotypes and tended to be smaller in the post-vs.-prevaccine than in the vaccinated-vs.-unvaccinated design. These results highlight that previously published epidemiological studies were not powerful enough to efficiently detect changes in nonvaccine-genotype prevalence.

Comparison of cohort and nested case-control designs for estimating the effect of time-varying drug exposure on the risk of adverse event in the presence of ties.

Cohort and nested case-control (NCC) designs are frequently used in pharmacoepidemiology to assess the associations of drug exposure that can vary over time with the risk of an adverse event. Although it is typically expected that estimates from NCC analyses are similar to those from the full cohort analysis, with moderate loss of precision, only few studies have actually compared their respective performance for estimating the effects of time-varying exposures (TVE). We used simulations to compare the properties of the resulting estimators of these designs for both time-invariant exposure and TVE. We varied exposure prevalence, proportion of subjects experiencing the event, hazard ratio, and control-to-case ratio and considered matching on confounders. Using both designs, we also estimated the real-world associations of time-invariant ever use of menopausal hormone therapy (MHT) at baseline and updated, time-varying MHT use with breast cancer incidence. In all simulated scenarios, the cohort-based estimates had small relative bias and greater precision than the NCC design. NCC estimates displayed bias to the null that decreased with a greater number of controls per case. This bias markedly increased with higher proportion of events. Bias was seen with Breslow's and Efron's approximations for handling tied event times but was greatly reduced with the exact method or when NCC analyses were matched on confounders. When analyzing the MHT-breast cancer association, differences between the two designs were consistent with simulated data. Once ties were taken correctly into account, NCC estimates were very similar to those of the full cohort analysis.

Identifying Protective Drugs for Parkinson's Disease in Health-Care Databases Using Machine Learning.

BACKGROUND: Available treatments for Parkinson's disease (PD) are only partially or transiently effective. Identifying existing molecules that may present a therapeutic or preventive benefit for PD (drug repositioning) is thus of utmost interest. OBJECTIVE: We aimed at detecting potentially protective associations between marketed drugs and PD through a large-scale automated screening strategy. METHODS: We implemented a machine learning (ML) algorithm combining subsampling and lasso logistic regression in a case-control study nested in the French national health data system. Our study population comprised 40,760 incident PD patients identified by a validated algorithm during 2016 to 2018 and 176,395 controls of similar age, sex, and region of residence, all followed since 2006. Drug exposure was defined at the chemical subgroup level, then at the substance level of the Anatomical Therapeutic Chemical (ATC) classification considering the frequency of prescriptions over a 2-year period starting 10 years before the index date to limit reverse causation bias. Sensitivity analyses were conducted using a more specific definition of PD status. RESULTS: Six drug subgroups were detected by our algorithm among the 374 screened. Sulfonamide diuretics (ATC-C03CA), in particular furosemide (C03CA01), showed the most robust signal. Other signals included adrenergics in combination with anticholinergics (R03AL) and insulins and analogues (A10AD). CONCLUSIONS: We identified several signals that deserve to be confirmed in large studies with appropriate consideration of the potential for reverse causation. Our results illustrate the value of ML-based signal detection algorithms for identifying drugs inversely associated with PD risk in health-care databases. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Nonoptimal Vaginal Microbiota After Azithromycin Treatment for Chlamydia trachomatis Infection.

We characterized the composition and structure of the vaginal microbiota in a cohort of 149 women with genital Chlamydia trachomatis infection at baseline who were followed quarterly for 9 months after antibiotic treatment. At time of diagnosis, the vaginal microbiota was dominated by Lactobacillus iners or a diverse array of bacterial vaginosis-associated bacteria including Gardnerella vaginalis. Interestingly, L. iners-dominated communities were most common after azithromycin treatment (1 g monodose), consistent with the observed relative resistance of L. iners to azithromycin. Lactobacillus iners-dominated communities have been associated with increased risk of C. trachomatis infection, suggesting that the impact of antibiotic treatment on the vaginal microbiota could favor reinfections. These results provide support for the dual need to account for the potential perturbing effect(s) of antibiotic treatment on the vaginal microbiota, and to develop strategies to protect and restore optimal vaginal microbiota.

Letermovir for Secondary Prophylaxis of Cytomegalovirus Infection and Disease after Allogeneic Hematopoietic Cell Transplantation: Results from the French Compassionate Program.

Letermovir potently inhibits the cytomegalovirus (CMV)-terminase complex. Letermovir primary prophylaxis given for the first 3 months after allogeneic hematopoietic cell transplantation (HCT) has been shown to reduce clinically significant CMV infection and is well tolerated. Until now, only case reports or small retrospective series have been published on the use of letermovir for a secondary prophylaxis (SP) of CMV infection or diseases after HCT. Here we report the outcome of 80 consecutive CMV-seropositive adult patients included in the French compassionate program and who received letermovir as a SP after at least 1 CMV episode (infection or disease) since HCT. Letermovir was initiated at a median of 170 (49 to 1829) days after transplant and given orally for a median of 118 (26 to 396) days at the usual daily dose of 480 mg once daily and adjusted to 240 mg once daily when coadministered with cyclosporine. The donors were seronegative in 53% of the cases. Fifty patients had a current or previous graft-versus-host disease (GVHD) and 14 had experienced CMV disease since transplant. Four (5.5%) patients developed CMV breakthrough infections (n = 1) or diseases (n = 3) after the initiation of letermovir. In 3 of these 4 patients, further investigation of virologic resistance showed a CMV UL56 mutation C325Y or W, conferring the high-level letermovir resistance. One or more adverse reactions were declared by the local investigator in 15 (19%) patients. Only 2 patients stopped letermovir SP because of an adverse reaction (pruritus, 1; cytopenia, 1). In our experience, letermovir given as a SP may prevent a new CMV reactivation in a high-risk patient population and can be administered for several weeks, providing a bridge between the pre-emptive or therapeutic treatment of a CMV episode and CMV-specific immune reconstitution, giving time for tapering immunosuppressants. Prospective studies are required to confirm these results.

Vaginal microbiota composition and association with prevalent Chlamydia trachomatis infection: a cross-sectional study of young women attending a STI clinic in France.

OBJECTIVES: New molecular techniques have allowed describing groups of bacterial communities in the vagina (community state types (CST)) that could play an important role in Chlamydia trachomatis (CT) infection. Our aim was to describe the distribution of CST in a population of young women in France. METHODS: A cross-sectional study was carried out in June 2015 among anonymous young women attending a STI clinic in Bordeaux, France. Participants provided a vaginal sample for CT screening and sociodemographic data. CT was diagnosed using the Aptima-combo 2 transcription-mediated-amplification assay. Vaginal microbiota composition was characterised using 16S rRNA gene amplicon sequencing. RESULTS: Microbiota composition and CT status were available for 132 women. CST dominated by Lactobacillus crispatus (CST-I), L. iners (CST-III) and a diversity of anaerobes (CST-IV) represented 37.1%, 38.6% and 22.0% of the sample, respectively. Twenty-one out of 132 women were CT positive. Proportions of CT-positive women were higher for samples belonging to CST-III (21.6%) and CST-IV (17.2%) than to CST-I (8.2%). CONCLUSIONS: Five CST were found in 132 young women from a STI clinic in France. These CSTs were not significantly associated with CT but higher proportions of CT-positive women were found in CST-III and CST-IV, consistent with a previous study in the Netherlands. Though our study lacked statistical power and was cross-sectional, it is a necessary first step to understand the structure of the vaginal microbiota in French women with or without infection before performing in-depth longitudinal studies.

A Cohort Study of Adolescent and Midlife Diet and Pancreatic Cancer Risk in the NIH-AARP Diet and Health Study.

Given the long latency period of pancreatic cancer, exploring the influence of early and midlife exposures will further advance our understanding of the disease. We assessed associations between diet and pancreatic cancer incidence in the National Institutes of Health (NIH)-AARP (formerly American Association of Retired Persons) Diet and Health Study. In 1996, a total of 303,094 participants completed 2 food frequency questionnaires that assessed diet at ages 12-13 years and 10 years previously. We used Cox proportional hazards regression to estimate adjusted hazard ratios and 95% confidence intervals. Through the end of 2006, a total of 1,322 pancreatic cancer cases occurred (average follow up time = 10.1 years). When comparing the highest tertiles with the lowest, carbohydrate intake during adolescence (hazard ratio (HR) = 0.87, 95% confidence interval (CI): 0.76, 0.99), but not 10 years before baseline, was inversely associated with pancreatic cancer risk. Total fat intake 10 years before baseline was significantly associated with increased risk (HR = 1.17, 95% CI: 1.02, 1.34), while risk was higher for high fat intake during both adolescence and midlife. Calcium intake 10 years before baseline was associated with reduced risk (HR = 0.87, 95% CI: 0.76, 0.99), as was a change from low intake in adolescence to high intake in midlife (HR = 0.71, 95% CI: 0.54, 0.93). Our study found a number of dietary factors present during adolescence and midlife to be associated with pancreatic cancer.

Comparison of methods for estimating the attributable risk in the context of survival analysis.

BACKGROUND: The attributable risk (AR) measures the proportion of disease cases that can be attributed to an exposure in the population. Several definitions and estimation methods have been proposed for survival data. METHODS: Using simulations, we compared four methods for estimating AR defined in terms of survival functions: two nonparametric methods based on Kaplan-Meier's estimator, one semiparametric based on Cox's model, and one parametric based on the piecewise constant hazards model, as well as one simpler method based on estimated exposure prevalence at baseline and Cox's model hazard ratio. We considered a fixed binary exposure with varying exposure probabilities and strengths of association, and generated event times from a proportional hazards model with constant or monotonic (decreasing or increasing) Weibull baseline hazard, as well as from a nonproportional hazards model. We simulated 1,000 independent samples of size 1,000 or 10,000. The methods were compared in terms of mean bias, mean estimated standard error, empirical standard deviation and 95% confidence interval coverage probability at four equally spaced time points. RESULTS: Under proportional hazards, all five methods yielded unbiased results regardless of sample size. Nonparametric methods displayed greater variability than other approaches. All methods showed satisfactory coverage except for nonparametric methods at the end of follow-up for a sample size of 1,000 especially. With nonproportional hazards, nonparametric methods yielded similar results to those under proportional hazards, whereas semiparametric and parametric approaches that both relied on the proportional hazards assumption performed poorly. These methods were applied to estimate the AR of breast cancer due to menopausal hormone therapy in 38,359 women of the E3N cohort. CONCLUSION: In practice, our study suggests to use the semiparametric or parametric approaches to estimate AR as a function of time in cohort studies if the proportional hazards assumption appears appropriate.

Management of Myelodysplastic Syndrome Relapsing after Allogeneic Hematopoietic Stem Cell Transplantation: A Study by the French Society of Bone Marrow Transplantation and Cell Therapies.

To find out prognostic factors and to investigate different therapeutic approaches, we report on 147 consecutive patients who relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS). Sixty-two patients underwent immunotherapy (IT group, second allo-HSCT or donor lymphocyte infusion), 39 received cytoreductive treatment alone (CRT group) and 46 were managed with palliative/supportive cares (PSC group). Two-year rates of overall survival (OS) were 32%, 6%, and 2% in the IT, CRT, and PSC groups, respectively (P < .001). In multivariate analysis, 4 factors adversely influenced 2-year rates of OS: history of acute graft-versus-host disease (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.26 to 2.67; P = .002), relapse within 6 months (HR, 2.69; 95% CI, .82 to 3.98; P < .001), progression to acute myeloid leukemia (HR, 2.59; 95% CI, 1.75 to 3.83; P < .001), and platelet count < 50 G/L at relapse (HR, 1.68; 95% CI, 1.15 to 2.44; P = .007). A prognostic score based on those factors discriminated 2 risk groups with median OSs of 13.2 versus 2.4 months, respectively (P < .001). When propensity score, prognostic score, and treatment strategy were included in Cox model, immunotherapy was found to be an independent factor that favorably impacts OS (HR, .40; 95% CI, .26 to .63; P < .001). In conclusion, immunotherapy should be considered when possible for MDS patients relapsing after allo-HSCT.

Detailed contact data and the dissemination of Staphylococcus aureus in hospitals.

Close proximity interactions (CPIs) measured by wireless electronic devices are increasingly used in epidemiological models. However, no evidence supports that electronically collected CPIs inform on the contacts leading to transmission. Here, we analyzed Staphylococcus aureus carriage and CPIs recorded simultaneously in a long-term care facility for 4 months in 329 patients and 261 healthcare workers to test this hypothesis. In the broad diversity of isolated S. aureus strains, 173 transmission events were observed between participants. The joint analysis of carriage and CPIs showed that CPI paths linking incident cases to other individuals carrying the same strain (i.e. possible infectors) had fewer intermediaries than predicted by chance (P < 0.001), a feature that simulations showed to be the signature of transmission along CPIs. Additional analyses revealed a higher dissemination risk between patients via healthcare workers than via other patients. In conclusion, S. aureus transmission was consistent with contacts defined by electronically collected CPIs, illustrating their potential as a tool to control hospital-acquired infections and help direct surveillance.

Dynamics of Epstein-Barr viral load after hematopoietic stem cell transplantation and effect of preemptive rituximab therapy.

BACKGROUND: Epstein-Barr virus (EBV) displays oncogenic properties, particularly in the immunocompromised host. Notably, hematopoietic stem cell transplantation (HSCT) recipients with a detectable blood EBV viral load (BEBVL) are considered at higher risk of post-transplant lymphoproliferative diseases (PTLD). Therefore, BEBVL is monitored after HSCT, and preemptive rituximab may be used in patients with high values. However, little is known about post-HSCT BEBVL dynamics, and the threshold that should lead to anti-CD20 therapy is poorly defined. METHODS: We retrospectively analyzed the post-HSCT BEBVL of 332 adult HSCT recipients in our center from 2005 to 2013, including the effect of rituximab. RESULTS: Detection of BEBVL >100, 1000, 5000, 10 000, and 50 000 copies/mL occurred in, respectively, 77.7%, 69.6%, 37.0%, 27.1%, and 7.5% of the patients after a respective median time of 9, 14, 15, 16, and 14 weeks. No BEBVL threshold was associated with an overall survival difference. Seventy-eight patients received rituximab, with a BEBVL decrease in most. Among patients with detectable BEBVL, long-term survival did not differ in rituximab treated and non-treated, except for patients with BEBVL ≥50 000. Only one case of PTLD was observed. CONCLUSIONS: BEBVL is frequently detectable after HSCT, but suggests no strong association with survival. Preemptive rituximab therapy threshold remains to be defined.

Fluoroquinolone Impact on Nasal Methicillin-Resistant and Methicillin-Sensitive Staphylococcus aureus Colonization Durations in Neurologic Long-Term-Care Facilities.

Staphylococcus aureus nasal carriage is a risk factor for subsequent infection. Estimates of colonization duration vary widely among studies, and factors influencing the time to loss of colonization, especially the impact of antibiotics, remain unclear. We conducted a prospective study on patients naive for S. aureus colonization in 4 French long-term-care facilities. Data on nasal colonization status and potential factors for loss of colonization were collected weekly. We estimated methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) colonization durations using the Kaplan-Meier method and investigated factors for loss of colonization using shared-frailty Cox proportional hazards models. A total of 285 S. aureus colonization episodes were identified in 149 patients. The median time to loss of MRSA or MSSA colonization was 3 weeks (95% confidence interval, 2 to 8 weeks) or 2 weeks (95% confidence interval, 2 to 3 weeks), respectively. In multivariable analyses, the methicillin resistance phenotype was not associated with S. aureus colonization duration (P = 0.21); the use of fluoroquinolones (hazard ratio, 3.37; 95% confidence interval, 1.31 to 8.71) and having a wound positive for a nonnasal strain (hazard ratio, 2.17; 95% confidence interval, 1.15 to 4.07) were associated with earlier loss of MSSA colonization, while no factor was associated with loss of MRSA colonization. These results suggest that the methicillin resistance phenotype does not influence the S. aureus colonization duration and that fluoroquinolones are associated with loss of MSSA colonization but not with loss of MRSA colonization.

Fluoroquinolone use is a risk factor for methicillin-resistant Staphylococcus aureus acquisition in long-term care facilities: a nested case-case-control study.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization is a well-established risk factor for subsequent infection and a key event in interindividual transmission. Some studies have showed an association between fluoroquinolones and MRSA colonization or infection. The present study was performed to identify specific risk factors for MRSA acquisition in long-term care facilities (LTCFs). METHODS: A prospective cohort of patients naive for S. aureus colonization was established and followed (January 2008 through October 2010) in 4 French LTCFs. Nasal colonization status and potential risk factors were assessed weekly for 13 weeks after inclusion. Variables associated with S. aureus acquisition were identified in a nested-matched case-case-control study using conditional logistic regression models. Cases were patients who acquired MRSA (or methicillin-sensitive S. aureus [MSSA]). Patients whose nasal swab samples were always negative served as controls. Matching criteria were center, date of first nasal swab sample, and exposure time. RESULTS: Among 451 included patients, 76 MRSA cases were matched to 207 controls and 112 MSSA cases to 208 controls. Multivariable analysis retained fluoroquinolones (odds ratio, 2.17; 95% confidence interval, 1.01-4.67), male sex (2.09; 1.10-3.98), and more intensive care at admission (3.24; 1.74-6.04) as significantly associated with MRSA acquisition, and body-washing assistance (2.85; 1.27-6.42) and use of a urination device (1.79; 1.01-3.18) as significantly associated with MSSA acquisition. CONCLUSIONS: Our results suggest that fluoroquinolones are a risk factor for MRSA acquisition. Control measures to limit MRSA spread in LTCFs should also be based on optimization of fluoroquinolone use.

Pneumocystis Pneumonia After Allogeneic Hematopoietic Cell Transplantation: A Case-Control Study on Epidemiology and Risk Factors on Behalf of the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation.

Pneumocystis pneumonia (PCP) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT). However, allo-HCT procedures have evolved toward older patients, unrelated donors, and reduced-intensity conditioning, possibly modifying the risks. Polymerase chain reaction (PCR), widely used nowadays, is more sensitive than microscopy diagnostic methods. This study aimed to assess the factors associated with PCP in allo-HCT recipients within 2 years of HCT and managed according to current procedures. This multicenter, nested case-control study included PCP cases diagnosed by PCR, cytology, or immunofluorescence on bronchoalveolar lavage fluid between 2016 and 2018. Two controls per case were selected from the ProMISe registry and matched for the center, transplant date, and underlying disease. Fifty-two cases and 104 controls were included among the 5452 patients who underwent allo-HCT in the participating centers. PCP occurred at a median of 11.5 months after transplantation. The mortality rate was 24% on day 30 after the PCP diagnosis and 37% on day 90. The clinical presentation and mortality rates of the 24 patients diagnosed using only PCR were not different from those diagnosed with microscopy methods. Our study demonstrates a substantial incidence of, and mortality from, PCP, after allogeneic HCT despite well-established prophylactic approaches. In our experience, PCP nowadays occurs later after transplant than previously reported, justifying the prolongation of prophylaxis after six months in many cases. Allo-HCT recipients diagnosed with PCR as the only PCP marker should benefit from specific treatment as for other patients.

A multistep voriconazole-related phototoxic pathway may lead to skin carcinoma: results from a French nationwide study.

BACKGROUND: Voriconazole long-term therapy is suspected to induce cutaneous squamous cell carcinoma (SCC), as suggested by 18 case reports worldwide and 3 retrospective studies. METHODS: To better characterize the natural history of these potentially voriconazole-associated tumors, a nationwide call for notification of skin cancers and other skin lesions observed between 2002 and 2012 in patients treated by voriconazole was launched in France. A multidisciplinary committee evaluated voriconazole involvement in each case. RESULTS: Nineteen SCCs were reported. The committee determined the likelihood of voriconazole involvement to be high in 15 cases, intermediate in 2, and low in 2. In the 17 patients with high/intermediate likelihood of voriconazole involvement, the mean time between voriconazole initiation and SCC diagnosis was 39 ± 18 months (range, 28-84 months), and was shorter in transplant recipients (35 vs 45 months, P < .05). Cumulative mean duration of voriconazole therapy at SCC diagnosis was 35 months (range, 7-63 months). A multistep process was noted in 14 of 17 patients: acute phototoxicity during the first year of voriconazole therapy (mean time, 6 months [range, 0-18 months]), actinic keratosis (AK) of the same sun-exposed skin area in the second/third year (mean, 30 months [range, 11-57 months]), followed by SCC during the third year or later. Five cases of AK without SCC and 37 cases of other skin lesions were also reported. CONCLUSIONS: Our results suggest that long-term voriconazole prescription may be associated with a multistep phototoxic process involving acute skin lesions followed by AK then by SCC. Discontinuation of voriconazole should be strongly considered in patients experiencing chronic phototoxicity.

Comparing human papillomavirus prevalences in women with normal cytology or invasive cervical cancer to rank genotypes according to their oncogenic potential: a meta-analysis of observational studies.

BACKGROUND: Mucosal human papillomavirus (HPV) infection is a necessary cause of cervical cancer. Vaccine and non-vaccine genotype prevalences may change after vaccine introduction. Therefore, it appears essential to rank HPV genotypes according to their oncogenic potential for invasive cervical cancer, independently of their respective prevalences. METHODS: We performed meta-analyses of published observational studies and estimated pooled odds ratios with random-effects models for 32 HPV genotypes, using HPV-16 as the reference. RESULTS: Twenty-seven studies yielded 9,252 HPV-infected women: 2,902 diagnosed with invasive cervical cancer and 6,350 with normal cytology. Expressed as (odds ratio [95% confidence interval]), HPV-18 (0.63 [0.51, 0.78]) ranked closest to HPV-16, while other genotypes showed continuously decreasing relative oncogenic potentials: HPV-45 (0.35 [0.22, 0.55]), HPV-69 (0.28 [0.09, 0.92]), HPV-58 (0.24 [0.15, 0.38]), HPV-31 (0.22 [0.14, 0.35]), HPV-33 (0.22 [0.12, 0.38]), HPV-34 (0.21 [0.06, 0.80]), HPV-67 (0.21 [0.06, 0.67]), HPV-39 (0.17 [0.09, 0.30]), HPV-59 (0.17 [0.09, 0.31]), HPV-73 (0.16 [0.06, 0.41]), and HPV-52 (0.16 [0.11, 0.23]). CONCLUSIONS: Our results support the markedly higher oncogenic potentials of HPV-16 and -18, followed by HPV-31, -33, -39, -45, -52, -58 and -59, and highlight the need for further investigation of HPV-34, -67, -69 and -73. Overall, these findings could have important implications for the prevention of cervical cancer.