Pub Date : 2019-06-01DOI: 10.1016/j.pvr.2019.02.004
Anne Hammer , Maurits NC de Koning , Jan Blaakaer , Torben Steiniche , John Doorbar , Heather Griffin , Else Mejlgaard , Hans Svanholm , Wim GV Quint , Patti E. Gravitt
In this study, we aimed to provide molecular evidence of HPV latency in humans and discuss potential challenges of conducting studies on latency. We analyzed the entire cervix of two women who underwent hysterectomy unrelated to cervical abnormality. The cervices were sectioned into 242 and 186 sets respectively, and each set was tested separately for HPV using the SPF10-PCR-DEIA-LiPA25 system. To identify whether there was any evidence of transforming or productive infection, we used the biomarkers E4 and P16INK4a to stain slides immediately adjacent to HPV-positive sections. HPV was detected in both cervices. In patient 1, 1/242 sets was positive for HPV31. In patient 2, 13/186 sets were positive for HPV18 and 1/186 was positive for HPV53. The infection was very focal in both patients, and there was no sign of a transforming or productive infection, as evaluated by the markers E4 and P16INK4a. Had we only analyzed one set from each block, the probability of detecting the infection would have been 32.3% and 2%, respectively.Our findings support the idea that HPV may be able to establish latency in the human cervix; however, the risk associated with a latent HPV infection remains unclear.
{"title":"Whole tissue cervical mapping of HPV infection: Molecular evidence for focal latent HPV infection in humans","authors":"Anne Hammer , Maurits NC de Koning , Jan Blaakaer , Torben Steiniche , John Doorbar , Heather Griffin , Else Mejlgaard , Hans Svanholm , Wim GV Quint , Patti E. Gravitt","doi":"10.1016/j.pvr.2019.02.004","DOIUrl":"10.1016/j.pvr.2019.02.004","url":null,"abstract":"<div><p>In this study, we aimed to provide molecular evidence of HPV latency in humans and discuss potential challenges of conducting studies on latency. We analyzed the entire cervix of two women who underwent hysterectomy unrelated to cervical abnormality. The cervices were sectioned into 242 and 186 sets respectively, and each set was tested separately for HPV using the SPF10-PCR-DEIA-LiPA25 system. To identify whether there was any evidence of transforming or productive infection, we used the biomarkers E4 and P16<sup>INK4a</sup> to stain slides immediately adjacent to HPV-positive sections. HPV was detected in both cervices. In patient 1, 1/242 sets was positive for HPV31. In patient 2, 13/186 sets were positive for HPV18 and 1/186 was positive for HPV53. The infection was very focal in both patients, and there was no sign of a transforming or productive infection, as evaluated by the markers E4 and P16<sup>INK4a</sup>. Had we only analyzed one set from each block, the probability of detecting the infection would have been 32.3% and 2%, respectively.Our findings support the idea that HPV may be able to establish latency in the human cervix; however, the risk associated with a latent HPV infection remains unclear.</p></div>","PeriodicalId":46835,"journal":{"name":"Papillomavirus Research","volume":"7 ","pages":"Pages 82-87"},"PeriodicalIF":3.2,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.pvr.2019.02.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36973617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-01DOI: 10.1016/j.pvr.2019.02.005
Alltalents T. Murahwa , Tracy L. Meiring , Zizipho Z.A. Mbulawa , Anna-Lise Williamson
Six novel human papillomaviruses from penile swabs were characterised. Multiple full genome clones for each novel type were generated, and complete genome sizes were: HPV211 (7253bp), HPV212 (7208bp), HPV213 (7096bp), HPV214 (7357), HPV215 (7186bp) and HPV216 (7233bp). Phylogenetically the novel papillomaviruses all clustered with Gammapapillomaviruses: HPV211 is most closely related to HPV168 (72% identity in the L1 nucleotide sequence) of the Gamma-8 species, HPV212 is most closely related to HPV144 (82.9%) of the Gamma-17 species, HPV213 is most closely related to HPV153 (71.8%) of the Gamma-13 species, HPV214 is most closely related to HPV103 (75.3%) of the Gamma-6 species, HPV215 and HPV216 are most closely related to HPV129 (76.8% and 79.2% respectively) of the Gamma-9 species. The novel HPV types demonstrated the classical genomic organisation of Gammapapillomavirusess, with seven open reading frames (ORFs) encoding five early (E1, E2, E4, E6 and E7) and two late (L1 and L2) proteins. Typical of Gammapapillomavirusess the novel types all lacked the E5 ORF and HPV214 also lacked the E6 ORF. HPV212 had nine unique variants, HPV213 had five and HPV215 had four variants. Conserved domains observed among the novel types are the Zinc finger Binding Domain and PDZ domains. A retinoblastoma binding domain (pRB) binding domain in E7 protein was additionally identified in HPV214. This study expands the knowledge of the rapidly growing Gammapapillomavirus genus.
{"title":"Discovery, characterisation and genomic variation of six novel Gammapapillomavirus types from penile swabs in South Africa","authors":"Alltalents T. Murahwa , Tracy L. Meiring , Zizipho Z.A. Mbulawa , Anna-Lise Williamson","doi":"10.1016/j.pvr.2019.02.005","DOIUrl":"10.1016/j.pvr.2019.02.005","url":null,"abstract":"<div><p>Six novel human papillomaviruses from penile swabs were characterised. Multiple full genome clones for each novel type were generated, and complete genome sizes were: HPV211 (7253bp), HPV212 (7208bp), HPV213 (7096bp), HPV214 (7357), HPV215 (7186bp) and HPV216 (7233bp). Phylogenetically the novel papillomaviruses all clustered with <em>Gammapapillomaviruses</em>: HPV211 is most closely related to HPV168 (72% identity in the L1 nucleotide sequence) of the Gamma-8 species, HPV212 is most closely related to HPV144 (82.9%) of the Gamma-17 species, HPV213 is most closely related to HPV153 (71.8%) of the Gamma-13 species, HPV214 is most closely related to HPV103 (75.3%) of the Gamma-6 species, HPV215 and HPV216 are most closely related to HPV129 (76.8% and 79.2% respectively) of the Gamma-9 species. The novel HPV types demonstrated the classical genomic organisation of <em>Gammapapillomaviruses</em>s, with seven open reading frames (ORFs) encoding five early (E1, E2, E4, E6 and E7) and two late (L1 and L2) proteins. Typical of <em>Gammapapillomavirusess</em> the novel types all lacked the E5 ORF and HPV214 also lacked the E6 ORF. HPV212 had nine unique variants, HPV213 had five and HPV215 had four variants. Conserved domains observed among the novel types are the Zinc finger Binding Domain and PDZ domains. A retinoblastoma binding domain (pRB) binding domain in E7 protein was additionally identified in HPV214. This study expands the knowledge of the rapidly growing <em>Gammapapillomavirus</em> genus.</p></div>","PeriodicalId":46835,"journal":{"name":"Papillomavirus Research","volume":"7 ","pages":"Pages 102-111"},"PeriodicalIF":3.2,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.pvr.2019.02.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37033715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-01DOI: 10.1016/j.pvr.2019.02.001
Gary M. Clifford , Vanessa Tenet , Damien Georges , Laia Alemany , Miquel Angel Pavón , Zigui Chen , Meredith Yeager , Michael Cullen , Joseph F. Boland , Sara Bass , Mia Steinberg , Tina Raine-Bennett , Thomas Lorey , Nicolas Wentzensen , Joan Walker , Rosemary Zuna , Mark Schiffman , Lisa Mirabello
Background
Human papillomavirus (HPV)16 can be separated into genetic sub-lineages (A1–4, B1–4, C1–4, D1–4) which may have differential cervical cancer risk.
Methods
A next-generation sequencing assay was used to whole-genome sequence 7116 HPV16-positive cervical samples from well-characterised international epidemiological studies, including 2076 controls, 1878 squamous cell carcinoma (SCC) and 186 adenocarcinoma/adenosquamous cell carcinoma (ADC), and to assign HPV16 sub-lineage. Logistic regression was used to estimate region-stratified country-adjusted odds ratios (OR) and 95%CI.
Results
A1 was the most globally widespread sub-lineage, with others showing stronger regional specificity (A3 and A4 for East Asia, B1–4 and C1–4 for Africa, D2 for the Americas, B4, C4 and D4 for North Africa). Increased cancer risks versus A1 were seen for A3, A4 and D (sub)lineages in regions where they were common: A3 in East Asia (OR=2.2, 95%CI:1.0–4.7); A4 in East Asia (6.6, 3.1–14.1) and North America (3.8, 1.7–8.3); and D in North (6.2, 4.1–9.3) and South/Central America (2.2, 0.8–5.7), where D lineages were also more frequent in ADC than SCC (3.2, 1.5–6.5; 12.1, 5.7–25.6, respectively).
Conclusions
HPV16 genetic variation can strongly influence cervical cancer risk. However, burden of cervical cancer attributable to different sub-lineages worldwide is largely driven by historical HPV16 sub-lineage dispersal.
{"title":"Human papillomavirus 16 sub-lineage dispersal and cervical cancer risk worldwide: Whole viral genome sequences from 7116 HPV16-positive women","authors":"Gary M. Clifford , Vanessa Tenet , Damien Georges , Laia Alemany , Miquel Angel Pavón , Zigui Chen , Meredith Yeager , Michael Cullen , Joseph F. Boland , Sara Bass , Mia Steinberg , Tina Raine-Bennett , Thomas Lorey , Nicolas Wentzensen , Joan Walker , Rosemary Zuna , Mark Schiffman , Lisa Mirabello","doi":"10.1016/j.pvr.2019.02.001","DOIUrl":"10.1016/j.pvr.2019.02.001","url":null,"abstract":"<div><h3>Background</h3><p>Human papillomavirus (HPV)16 can be separated into genetic sub-lineages (A1–4, B1–4, C1–4, D1–4) which may have differential cervical cancer risk.</p></div><div><h3>Methods</h3><p>A next-generation sequencing assay was used to whole-genome sequence 7116 HPV16-positive cervical samples from well-characterised international epidemiological studies, including 2076 controls, 1878 squamous cell carcinoma (SCC) and 186 adenocarcinoma/adenosquamous cell carcinoma (ADC), and to assign HPV16 sub-lineage. Logistic regression was used to estimate region-stratified country-adjusted odds ratios (OR) and 95%CI.</p></div><div><h3>Results</h3><p>A1 was the most globally widespread sub-lineage, with others showing stronger regional specificity (A3 and A4 for East Asia, B1–4 and C1–4 for Africa, D2 for the Americas, B4, C4 and D4 for North Africa). Increased cancer risks versus A1 were seen for A3, A4 and D (sub)lineages in regions where they were common: A3 in East Asia (OR=2.2, 95%CI:1.0–4.7); A4 in East Asia (6.6, 3.1–14.1) and North America (3.8, 1.7–8.3); and D in North (6.2, 4.1–9.3) and South/Central America (2.2, 0.8–5.7), where D lineages were also more frequent in ADC than SCC (3.2, 1.5–6.5; 12.1, 5.7–25.6, respectively).</p></div><div><h3>Conclusions</h3><p>HPV16 genetic variation can strongly influence cervical cancer risk. However, burden of cervical cancer attributable to different sub-lineages worldwide is largely driven by historical HPV16 sub-lineage dispersal.</p></div>","PeriodicalId":46835,"journal":{"name":"Papillomavirus Research","volume":"7 ","pages":"Pages 67-74"},"PeriodicalIF":3.2,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.pvr.2019.02.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36946630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-01DOI: 10.1016/j.pvr.2019.04.011
Silvia de Sanjose, Francesca Holme
Effective screening for pre-cancerous lesions of the cervix is the only protective intervention that can be offered to women that have not had the opportunity to be vaccinated. Elimination goals are being developed so that by 2030, 70% of women aged 35–45 years should have been screened at least once in a lifetime and 90% of all detected lesions should have been treated. These goals focus on a substantial reduction of cervical cancer burden in low- and middle-income countries (LMICs). Scaling-up screening in these settings may be substantially improved by using self-sampling (SS), human papillomavirus (HPV) testing, and managing screened-positive women with accessible treatment. The implementation of these tools requires minimal health information data for traceability, provider training, community education, operational management and quality control. Cost-effective algorithms tailored to country needs can greatly impact the burden of disease in a limited number of years.
{"title":"What is needed now for successful scale-up of screening?","authors":"Silvia de Sanjose, Francesca Holme","doi":"10.1016/j.pvr.2019.04.011","DOIUrl":"10.1016/j.pvr.2019.04.011","url":null,"abstract":"<div><p>Effective screening for pre-cancerous lesions of the cervix is the only protective intervention that can be offered to women that have not had the opportunity to be vaccinated. Elimination goals are being developed so that by 2030, 70% of women aged 35–45 years should have been screened at least once in a lifetime and 90% of all detected lesions should have been treated. These goals focus on a substantial reduction of cervical cancer burden in low- and middle-income countries (LMICs). Scaling-up screening in these settings may be substantially improved by using self-sampling (SS), human papillomavirus (HPV) testing, and managing screened-positive women with accessible treatment. The implementation of these tools requires minimal health information data for traceability, provider training, community education, operational management and quality control. Cost-effective algorithms tailored to country needs can greatly impact the burden of disease in a limited number of years.</p></div>","PeriodicalId":46835,"journal":{"name":"Papillomavirus Research","volume":"7 ","pages":"Pages 173-175"},"PeriodicalIF":3.2,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.pvr.2019.04.011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37167793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-01DOI: 10.1016/j.pvr.2019.03.001
Andres Castillo , Julio Cesar Osorio , Adrián Fernández , Fabián Méndez , Liliana Alarcón , Gabriela Arturo , Rolando Herrero , Luis Eduardo Bravo
Introduction
In recent years, an association between HPV-16 and oropharyngeal cancers has been reported. Therefore, it is necessary to evaluate whether vaccination decreases the exposure of HPV-16 in the oral cavity.
Objective
To evaluate the effect of vaccination on oral HPV-16 infection in high school students in the city of Cali, Colombia.
Methods
In this cross-sectional study, HPV-16 DNA was detected in samples from the oral cavity and throat of 1,784 high school students of both genders, aged 14–17 years old, in 21 schools in the city of Cali, Colombia. The number in vaccinated girls were 944 vs., 95 unvaccinated girls and 745 unvaccinated boys.
Results
The HPV exposure percentages were: 0.7% in vaccinated girls, 3.2% in unvaccinated girls and 2.3% in unvaccinated boys. The odds ratio (OR) of detection of HPV-16 in vaccinated versus unvaccinated students was 0.28 (95% CI: 0.07–0.88), representing a 72% reduction in HPV-16 detection in students immunized with two doses. The odds of detection of HPV-16 in unvaccinated male students were 3.6 times those of vaccinated girls (OR = 3.6, 95% CI: 1.21–12.81) and increased to almost eight-fold in boys who had initiated sexual activity (OR = 7.74, 95% CI: 1.53–75.09).
Conclusions
HPV vaccination was associated with the reduction of HPV-16 exposure percentages in the oral and oropharyngeal cavity.
{"title":"Effect of vaccination against oral HPV-16 infection in high school students in the city of Cali, Colombia","authors":"Andres Castillo , Julio Cesar Osorio , Adrián Fernández , Fabián Méndez , Liliana Alarcón , Gabriela Arturo , Rolando Herrero , Luis Eduardo Bravo","doi":"10.1016/j.pvr.2019.03.001","DOIUrl":"10.1016/j.pvr.2019.03.001","url":null,"abstract":"<div><h3>Introduction</h3><p>In recent years, an association between HPV-16 and oropharyngeal cancers has been reported. Therefore, it is necessary to evaluate whether vaccination decreases the exposure of HPV-16 in the oral cavity.</p></div><div><h3>Objective</h3><p>To evaluate the effect of vaccination on oral HPV-16 infection in high school students in the city of Cali, Colombia.</p></div><div><h3>Methods</h3><p>In this cross-sectional study, HPV-16 DNA was detected in samples from the oral cavity and throat of 1,784 high school students of both genders, aged 14–17 years old, in 21 schools in the city of Cali, Colombia. The number in vaccinated girls were 944 vs., 95 unvaccinated girls and 745 unvaccinated boys.</p></div><div><h3>Results</h3><p>The HPV exposure percentages were: 0.7% in vaccinated girls, 3.2% in unvaccinated girls and 2.3% in unvaccinated boys. The odds ratio (OR) of detection of HPV-16 in vaccinated versus unvaccinated students was 0.28 (95% CI: 0.07–0.88), representing a 72% reduction in HPV-16 detection in students immunized with two doses. The odds of detection of HPV-16 in unvaccinated male students were 3.6 times those of vaccinated girls (OR = 3.6, 95% CI: 1.21–12.81) and increased to almost eight-fold in boys who had initiated sexual activity (OR = 7.74, 95% CI: 1.53–75.09).</p></div><div><h3>Conclusions</h3><p>HPV vaccination was associated with the reduction of HPV-16 exposure percentages in the oral and oropharyngeal cavity.</p></div>","PeriodicalId":46835,"journal":{"name":"Papillomavirus Research","volume":"7 ","pages":"Pages 112-117"},"PeriodicalIF":3.2,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.pvr.2019.03.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37199998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-01DOI: 10.1016/j.pvr.2018.12.004
Amrei Krings , Gifty Boateng , Priscilla Dunyo , Joseph E. Amuah , Rashid A. Adams , Lois Adunyame , Dinah O. Nkansah , Comfort M. Wormenor , Benjamin T. Hansen , Isaac Gedzah , Richard H. Asmah , Edwin K. Wiredu , Andreas M. Kaufmann
Persistent Human Papillomavirus (HPV) infection is a prerequisite for cervical cancer development. Few studies investigated clearance of high-risk HPV in low-and-middle-income countries. Our study investigated HPV clearance and persistence over four years in women from North Tongu District, Ghana.
In 2010/2011, cervical swabs of 500 patients were collected and HPV genotyped (nested multiplex PCR) in Accra, Ghana. In 2014, 104 women who previously tested positive for high-risk HPV and remained untreated were re-tested for HPV. Cytobrush samples were genotyped (GP5+/6+ PCR & Luminex-MPG readout) in Berlin, Germany. Positively tested patients underwent colposcopy and treatment if indicated.
Of 104 women, who tested high-risk HPV+ in 2010/2011, seven (6,7%; 95%CI: 2.7–13.4%) had ≥1 persistent high-risk‐infection after ~4 years (mean age 39 years). Ninety-seven (93,3%; 95%CI: 86.6–97.3%) had cleared the original infection, while 22 (21.2%; 95%CI: 13.8–30.3%) had acquired new high-risk infections with other genotypes. Persistent types found were HPV 16, 18, 35, 39, 51, 52, 58, and 68. Among those patients, one case of CIN2 (HPV 68) and one micro-invasive cervical cancer (HPV 16) were detected.
This longitudinal observational data suggest that single HPV screening rounds may lead to over-referral. Including type-specific HPV re-testing or additional triage methods could help reduce follow-up rates.
{"title":"Dynamics of genotype-specific HPV clearance and reinfection in rural Ghana may compromise HPV screening approaches","authors":"Amrei Krings , Gifty Boateng , Priscilla Dunyo , Joseph E. Amuah , Rashid A. Adams , Lois Adunyame , Dinah O. Nkansah , Comfort M. Wormenor , Benjamin T. Hansen , Isaac Gedzah , Richard H. Asmah , Edwin K. Wiredu , Andreas M. Kaufmann","doi":"10.1016/j.pvr.2018.12.004","DOIUrl":"10.1016/j.pvr.2018.12.004","url":null,"abstract":"<div><p>Persistent Human Papillomavirus (HPV) infection is a prerequisite for cervical cancer development. Few studies investigated clearance of high-risk HPV in low-and-middle-income countries. Our study investigated HPV clearance and persistence over four years in women from North Tongu District, Ghana.</p><p>In 2010/2011, cervical swabs of 500 patients were collected and HPV genotyped (nested multiplex PCR) in Accra, Ghana. In 2014, 104 women who previously tested positive for high-risk HPV and remained untreated were re-tested for HPV. Cytobrush samples were genotyped (GP5+/6+ PCR & Luminex-MPG readout) in Berlin, Germany. Positively tested patients underwent colposcopy and treatment if indicated.</p><p>Of 104 women, who tested high-risk HPV+ in 2010/2011, seven (6,7%; 95%CI: 2.7–13.4%) had ≥1 persistent high-risk‐infection after ~4 years (mean age 39 years). Ninety-seven (93,3%; 95%CI: 86.6–97.3%) had cleared the original infection, while 22 (21.2%; 95%CI: 13.8–30.3%) had acquired new high-risk infections with other genotypes. Persistent types found were HPV 16, 18, 35, 39, 51, 52, 58, and 68. Among those patients, one case of CIN2 (HPV 68) and one micro-invasive cervical cancer (HPV 16) were detected.</p><p>This longitudinal observational data suggest that single HPV screening rounds may lead to over-referral. Including type-specific HPV re-testing or additional triage methods could help reduce follow-up rates.</p></div>","PeriodicalId":46835,"journal":{"name":"Papillomavirus Research","volume":"7 ","pages":"Pages 45-51"},"PeriodicalIF":3.2,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.pvr.2018.12.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36848608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-01DOI: 10.1016/j.pvr.2019.04.008
Pascal van der Weele , Audrey J. King , Chris J.L.M. Meijer , Renske D.M. Steenbergen
Introduction
Recurrent cervical intraepithelial lesions (rCIN2/3) after treatment of CIN2/3 occur in 5–15% of cases. rCIN2/3 can result from incomplete resection of CIN2/3, where the same HPV type and variant remains present. rCIN2/3 could also occur following a new infection with a different HPV variant of the same HPV type as the initial lesion. This study investigates HPV16 consensus variants in paired HPV16 positive scrapes from baseline CIN2/3 and rCIN2/3 lesions.
Methods
Paired HPV16 positive cervical scrapes of women with CIN2/3 at baseline and rCIN2/3 6 or 12 months after treatment were selected for whole-genome amplification and Illumina sequencing. Sequences were compared and nucleotide changes over time were characterized.
Results
From 14 paired samples, 10 had identical consensus variants in baseline CIN2/3 and rCIN2/3. Four paired samples showed one to three nucleotide variations at recurrent disease compared to baseline.
Conclusion
Identical or nearly identical HPV16 consensus variants were found in scrapes of paired HPV16 positive baseline CIN2/3 and rCIN2/3 lesions after treatment, suggesting no need for HPV variant analysis when the same HPV type is found in both lesions. These results argue for either incomplete excision of baseline CIN2/3 or inability of clearance of the original HPV infection.
{"title":"HPV16 variant analysis in primary and recurrent CIN2/3 lesions demonstrates presence of the same consensus variant","authors":"Pascal van der Weele , Audrey J. King , Chris J.L.M. Meijer , Renske D.M. Steenbergen","doi":"10.1016/j.pvr.2019.04.008","DOIUrl":"10.1016/j.pvr.2019.04.008","url":null,"abstract":"<div><h3>Introduction</h3><p>Recurrent cervical intraepithelial lesions (rCIN2/3) after treatment of CIN2/3 occur in 5–15% of cases. rCIN2/3 can result from incomplete resection of CIN2/3, where the same HPV type and variant remains present. rCIN2/3 could also occur following a new infection with a different HPV variant of the same HPV type as the initial lesion. This study investigates HPV16 consensus variants in paired HPV16 positive scrapes from baseline CIN2/3 and rCIN2/3 lesions.</p></div><div><h3>Methods</h3><p>Paired HPV16 positive cervical scrapes of women with CIN2/3 at baseline and rCIN2/3 6 or 12 months after treatment were selected for whole-genome amplification and Illumina sequencing. Sequences were compared and nucleotide changes over time were characterized.</p></div><div><h3>Results</h3><p>From 14 paired samples, 10 had identical consensus variants in baseline CIN2/3 and rCIN2/3. Four paired samples showed one to three nucleotide variations at recurrent disease compared to baseline.</p></div><div><h3>Conclusion</h3><p>Identical or nearly identical HPV16 consensus variants were found in scrapes of paired HPV16 positive baseline CIN2/3 and rCIN2/3 lesions after treatment, suggesting no need for HPV variant analysis when the same HPV type is found in both lesions. These results argue for either incomplete excision of baseline CIN2/3 or inability of clearance of the original HPV infection.</p></div>","PeriodicalId":46835,"journal":{"name":"Papillomavirus Research","volume":"7 ","pages":"Pages 168-172"},"PeriodicalIF":3.2,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.pvr.2019.04.008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37157595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-01DOI: 10.1016/j.pvr.2019.03.002
Murat Gultekin , Mujdegul Zayifoglu Karaca , Irem Kucukyildiz , Selin Dundar , Bekir Keskinkilic , Murat Turkyilmaz
Cervical cancer is the fourth most common cancer among women in the world. It is estimated that one woman dies every 2 min from cervical cancer. Nearly all cervical cancers are preventable by early detection and treatment through screening or HPV vaccination. In 2018, World Health Organization (WHO) made a global call for action toward the elimination of cervical cancer. Cervical cancer screening involves a complex organized program, which begins with a call/recall system based on personal invitation of eligible women, followed by participation in screening, and leading to diagnosis, treatment, and management as appropriate. An effective cervical screening program with high coverage is dependent on each country's infrastructure and human resource capacity. Efforts to develop an effective program is particularly challenging in low and middle income countries (LMIC) where resources are limited. For an effective strategy, Turkey redesigned the country's cervical screening program. The local call/recall system and centralized monitoring system of individual women were re-vamped with an automated evaluation system. The revised screening program includes the use of primary HPV testing with a well-defined protocol outlining the algorithms of management (i.e., screening intervals and referral), a single nationwide centralized diagnostic laboratory, and a sustainable agreement with the HPV diagnostics industry. This system allows for traceable, real-time monitoring of screening visits and specimens. Turkey reports on the first four years of this re-vamped organized program and shares lessons learnt from the implementation of this new program.
{"title":"Mega Hpv laboratories for cervical cancer control: Challenges and recommendations from a case study of Turkey","authors":"Murat Gultekin , Mujdegul Zayifoglu Karaca , Irem Kucukyildiz , Selin Dundar , Bekir Keskinkilic , Murat Turkyilmaz","doi":"10.1016/j.pvr.2019.03.002","DOIUrl":"10.1016/j.pvr.2019.03.002","url":null,"abstract":"<div><p>Cervical cancer is the fourth most common cancer among women in the world. It is estimated that one woman dies every 2 min from cervical cancer. Nearly all cervical cancers are preventable by early detection and treatment through screening or HPV vaccination. In 2018, World Health Organization (WHO) made a global call for action toward the elimination of cervical cancer. Cervical cancer screening involves a complex organized program, which begins with a call/recall system based on personal invitation of eligible women, followed by participation in screening, and leading to diagnosis, treatment, and management as appropriate. An effective cervical screening program with high coverage is dependent on each country's infrastructure and human resource capacity. Efforts to develop an effective program is particularly challenging in low and middle income countries (LMIC) where resources are limited. For an effective strategy, Turkey redesigned the country's cervical screening program. The local call/recall system and centralized monitoring system of individual women were re-vamped with an automated evaluation system. The revised screening program includes the use of primary HPV testing with a well-defined protocol outlining the algorithms of management (i.e., screening intervals and referral), a single nationwide centralized diagnostic laboratory, and a sustainable agreement with the HPV diagnostics industry. This system allows for traceable, real-time monitoring of screening visits and specimens. Turkey reports on the first four years of this re-vamped organized program and shares lessons learnt from the implementation of this new program.</p></div>","PeriodicalId":46835,"journal":{"name":"Papillomavirus Research","volume":"7 ","pages":"Pages 118-122"},"PeriodicalIF":3.2,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.pvr.2019.03.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37224195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-06-01DOI: 10.1016/j.pvr.2019.04.003
Massimo Tommasino
Epidemiological and biological studies provide several lines of evidence for the involvement of cutaneous beta human papillomaviruses (HPVs), together with ultraviolet (UV) radiation, in the development of cutaneous squamous cell carcinoma. These viruses appear to act with a hit-and-run mechanism, being necessary at an early stage of carcinogenesis and being dispensable for the maintenance of the malignant phenotype. Studies in experimental models show that beta HPVs, mainly via the E6 and E7 oncoproteins, are able to promote proliferation and to circumvent cellular stresses induced by UV radiation. These findings support a model of skin carcinogenesis in which beta HPV-infected keratinocytes remain alive despite the accumulation of UV-induced DNA mutations. In this manner, these cells become highly susceptible to progression towards malignancy. Thus, UV radiation is the main driver of skin cancer development, while beta HPVs act as facilitators of the accumulation of UV-induced DNA mutations.
{"title":"HPV and skin carcinogenesis","authors":"Massimo Tommasino","doi":"10.1016/j.pvr.2019.04.003","DOIUrl":"10.1016/j.pvr.2019.04.003","url":null,"abstract":"<div><p>Epidemiological and biological studies provide several lines of evidence for the involvement of cutaneous beta human papillomaviruses (HPVs), together with ultraviolet (UV) radiation, in the development of cutaneous squamous cell carcinoma. These viruses appear to act with a hit-and-run mechanism, being necessary at an early stage of carcinogenesis and being dispensable for the maintenance of the malignant phenotype. Studies in experimental models show that beta HPVs, mainly via the E6 and E7 oncoproteins, are able to promote proliferation and to circumvent cellular stresses induced by UV radiation. These findings support a model of skin carcinogenesis in which beta HPV-infected keratinocytes remain alive despite the accumulation of UV-induced DNA mutations. In this manner, these cells become highly susceptible to progression towards malignancy. Thus, UV radiation is the main driver of skin cancer development, while beta HPVs act as facilitators of the accumulation of UV-induced DNA mutations.</p></div>","PeriodicalId":46835,"journal":{"name":"Papillomavirus Research","volume":"7 ","pages":"Pages 129-131"},"PeriodicalIF":3.2,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.pvr.2019.04.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37288662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}