cis-3,3-Dimethyl-3,3a,4,5,6,6a-hexa­hydro-1H-cyclo­penta­[c]furan-1,6-dione

The bicyclic mol­ecule of the title compound, C9H12O3, contains two five-membered rings with different functional groups, viz. a ketone and an ester. Both rings assume an envelope conformation. The mean planes of these functional groups form a dihedral angle of 60.7 (1)°. The crystal structure exhibits weak inter­molecular C—H⋯O inter­actions, which link the mol­ecules into zigzag chains extended in the [010] direction. The unit cell contains a racemic mixture of enanti­omers

Strategies for the introduction of human papillomavirus vaccination: modelling the optimum age- and sex-specific pattern of vaccination in Finland

Phase III trials have demonstrated the efficacy of human papillomavirus (HPV) vaccines in preventing transient and persistent high-risk (hr) HPV infection and precancerous lesions. A mathematical model of HPV type 16 infection and progression to cervical cancer, parameterised to represent the infection in Finland, was used to explore the optimal age at vaccination and pattern of vaccine introduction. In the long term, the annual proportion of cervical cancer cases prevented is much higher when early adolescents are targeted. Vaccinating against hr HPV generates greater long-term benefits if vaccine is delivered before the age at first sexual intercourse. However, vaccinating 12 year olds delays the predicted decrease in cervical cancer, compared to vaccinating older adolescents or young adults. Vaccinating males as well as females has more impact on the proportion of cases prevented when vaccinating at younger ages. Implementing catch-up vaccination at the start of a vaccination programme would increase the speed with which a decrease in HPV and cervical cancer incidence is observed

Elimination of HPV-associated oropharyngeal cancers in Nordic countries

Incidence of human papillomavirus (HPV, most notably HPV type 16) associated oropharyngeal squamous cell carcinoma (OPSCC) among middle-aged (50?69 year-old) males has tripled in four high income Nordic countries (Denmark, Finland, Norway and Sweden) over the last 30 years. In Finland and Sweden, this increase was preceded by an HPV16 epidemic in fertile-aged populations in the 1980?s. The recent implementation of school based prophylactic HPV vaccination in early adolescent boys and girls will gradually decrease the incidence, and eventually eliminate the HPV-associated OPSCCs (especially tonsillar and base of tongue carcinomas) in the Nordic countries. However, beyond the adolescent and young adult birth cohorts vaccinated, there are approximately 50 birth cohorts (born in 1995 or before) that would benefit from screening for HPV-associated OPSCC. This article reviews the need, prerequisites, proof-of-concept trial and prospects of preventing HPVassociated OPSCC in the Nordic countries.Peer reviewe

A prospective study of the relationship between prediagnostic Human Papillomavirus seropositivity and HPV DNA in subsequent cervical carcinomas

Several prospective studies with invasive carcinoma as endpoint have supported Human Papillomavirus as a cause of cervical carcinoma. However, the largest study used seroepidemiology and did not analyse presence of Human Papillomavirus DNA in the subsequent tumour. Linkage of serum bank registries and cancer registries had identified 196 women with a registered cervical carcinoma after donation of a serum sample. For the present study, biopsies for 127 cases could be located, verified to contain invasive carcinoma and be amplified by PCR. Three control women who had remained alive and without cervical carcinoma during an equal length of follow-up had been matched to each of the case women and tested for HPV antibodies. Presence of Human Papillomavirus DNA in the tumours was analysed by general primer and type specific PCR. HPV16-seropositive women had a relative risk of 4.4 (95% CI: 2.2–8.8) to develop cervical carcinoma carrying HPV16 DNA. By contrast, there was no excess risk for Human Papillomavirus 16-seropositive women to develop cervical carcinoma devoid of HPV16 DNA. Prediagnostic HPV16 seropositivity was strongly correlated with later HPV16 DNA positivity of the tumour (P<0.001) and prediagnostic HPV18 seropositivity correlated with HPV18 DNA in the tumour (P<0.03). The link between prediagnostic seropositivity and type of viral DNA in the cancer implies that the carcinogenic effect of infection with these viruses is dependent on persistent presence of type-specific viral DNA

Age-specific HPV type distribution in high-grade cervical disease in screened and unvaccinated women

Background and aim. Age-specific type-distribution of high-risk human papillomavirus (hrHPV) in cervical precancerous lesions is subject to change in the HPV vaccination era. Knowing the pre-vaccination type distribution helps to anticipate changes induced by mass vaccination and optimize screening.Methods. We recruited 1279 women referred to colposcopy for abnormal cytology into a population-based study on HPV type distribution in diagnostic cervical samples (ISRCTN10933736). The HPV genotyping findings were grouped as: HPV16/18+, other hrHPV+ (HPV31/33/35/39/45/51/52/56/58/59/66/68), non-vaccine targeted hrHPV+ (HPV35/39/51/56/59/66/68), low-risk HPV, and HPV negative. We estimated the HPV group-specific prevalence rates according to diagnostic histopathological findings in the age groups of = 45 (n = 326).Results. Altogether 503 cases with high grade squamous intraepithelial lesion or worse (HSIL+) were diagnosed. More than half, 285 (56.7%) of HSIL+ cases were associated with HPV16/18: 64.3% (101/157) in women = 45 years of age (RR 0.55, 95% CI 039-0.75). Conversely, other hrHPV's were associated with 191 (38.0%) of HSIL+: 31.9% (50/157) in women = 45 (RR 1.71, 95% CI 126-2.33). The proportion of non-vaccine targeted hrHPV and HPV negative HSIL+ increased with advancing age.Conclusions. Pre-vaccination HPV type distribution in HSIL+ was distinctly polarised by age with HPV16/18 attributed disease being markedly more prevalent in women aged <30. In the older women the other hrHPV types, however, dominated suggesting a need for more age-dependent screening strategies. (C) 2019 The Authors. Published by Elsevier Inc

Low methylation marker levels among human papillomavirus-vaccinated women with cervical high-grade squamous intraepithelial lesions.

Cervical cancer screening programs, including triage tests, need redesigning as human papillomavirus (HPV)-vaccinated women are entering the programs. Methylation markers offer a potential solution to reduce false-positive rates by identifying clinically relevant cervical lesions with progressive potential. In a nested case-control study, 9242 women who received the three-dose HPV16/18-vaccine at ages 12-15 or 18 in a community-randomized trial were included. Subsequently, they were re-randomized for either frequent or infrequent cervical cancer screening trials. Over a 15-year post-vaccination follow-up until 2022, 17 high-grade squamous intraepithelial lesion (HSIL) and 15 low-grade (LSIL) cases were identified at the 25-year screening round, alongside 371 age and community-matched HPV16/18-vaccinated controls. Methylation analyses were performed on cervical samples collected at age 25, preceding histologically confirmed LSIL or HSIL diagnoses. DNA methylation of viral (HPV16/18/31/33) and host-cell genes (EPB41L3, FAM19A4, and miR124-2) was measured, along with HPV-genotyping. No HPV16/18 HSIL cases were observed. The predominant HPV-genotypes were HPV52 (29.4%), HPV59/HPV51/HPV58 (each 23.5%), and HPV33 (17.7%). Methylation levels were generally low, with no significant differences in mean methylation levels of viral or host-cell genes between the LSIL/HSIL and controls. However, a significant difference in methylation levels was found between HSIL cases and controls when considering a combination of viral genes and EPB41L3 (p value = .0001). HPV-vaccinated women with HSIL had HPV infections with uncommon HPV types that very rarely cause cancer and displayed low methylation levels. Further investigation is warranted to understand the likely regressive nature of HSIL among HPV-vaccinated women and its implications for management

Stability assessment of organic sulfur and organosulfate compounds in filter samples for quantification by Fourier- transform infrared spectroscopy

Organic sulfur and sulfate compounds, which are tracers for sources and atmospheric processes, are not currently measured in national monitoring networks such as the Interagency Monitoring of Protected Visual Environments (IMPROVE). The goal of this paper is to begin to assess the stability of organic sulfur and sulfate-containing compounds on polytetrafluoroethylene (PTFE) filters and the suitability of Fourier-transform infrared (FT-IR) spectroscopy to measure these compounds. Stability assessment is needed because PTFE samples collected by IMPROVE are typically stored 6–9 months prior to analysis. For this study, two organosulfur compounds, methanesulfonic acid (MSA) and hydroxymethanesulfonate ion (HMS), and two organosulfate compounds, methyl sulfate (MS) and 2-methyltetrol sulfate (2-MTS), are collected individually on PTFE filters. Gravimetric mass measurements are used to assess mass stability over time. FT-IR spectra are evaluated to assess the capability of measuring the compound from PTFE filters by assessing the compound stability or chemical changes over time. Ion chromatography (IC) and inductively coupled plasma optical emission spectroscopy (ICP-OES) are used as additional tools to assess stability or chemical changes over time. MS has the highest potential to be measured by FT-IR in IMPROVE samples. For MS, a simple organosulfate, the mass changes are within measurement uncertainty and FT-IR spectra indicate no compositional change over a 4-month period, suggesting that MS can be measured using FT-IR. IC and ICP-OES support the conclusion that MS is stable on the filter. However, for 2-MTS, the other organosulfate measured in this study, spectral changes after a month on the filter suggest that it decomposes into other organosulfates or an inorganic sulfate. MSA in IMPROVE samples can be measured, but only as a lower bound, due to volatility off the filter as indicated by FT-IR and gravimetry. FT-IR and IC both show that MSA does not chemically change over the course of the study. Measurements by all methods indicate that HMS is unstable on the PTFE filter, and IC and FT-IR indicate that it likely converts to inorganic sulfate. Future work includes the evaluation of these compounds in an ambient aerosol sample matrix to determine any differences in stability, identifying interference that could limit quantification, and developing calibrations to measure the compounds or functional groups in ambient samples.</p

Prevalence of human papillomavirus antibodies in young female subjects in England

Sera from 1483 female subjects in England aged 10–29 years were tested. The age-standardised seroprevalence was 10.7% (95% confidence intervals 9.0–12.3) for human papillomavirus (HPV) 6, 2.7% (1.8–3.6) for HPV 11, 11.9% (10.2–13.6) for HPV 16, 4.7% (3.5–5.8) for HPV 18, and 20.7% (18.6–22.7) for any of the four types