Carcinogenic human papillomavirus infection

Schiffman, Mark; Doorbar, John; Wentzensen, Nicolas; Sanjosé, Sílvia de; Fakhry, Carole; Monk, Bradley J.; Stanley, Margaret; Franceschi, Silvia

doi:10.1038/nrdp.2016.86

Cited by 716 publications

(769 citation statements)

References 202 publications

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“…The most important HPV‐induced malignancy is cervical cancer, which is the fourth most common cancer in women worldwide 6. The vast majority of cervical cancer is caused by HPV16 and HPV18 (60 and 15% of cases, respectively) 6, 7. The likelihood to get infected with a high‐risk HPV type and consequently develop cancer was reduced after prophylactic vaccines became available for immunization of adolescents in 2006 8.…”

Section: Introductionmentioning

confidence: 99%

A Targeted LC‐MS Strategy for Low‐Abundant HLA Class‐I‐Presented Peptide Detection Identifies Novel Human Papillomavirus T‐Cell Epitopes

et al. 2018

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For rational design of therapeutic vaccines, detailed knowledge about target epitopes that are endogenously processed and truly presented on infected or transformed cells is essential. Many potential target epitopes (viral or mutation‐derived), are presented at low abundance. Therefore, direct detection of these peptides remains a challenge. This study presents a method for the isolation and LC‐MS3‐based targeted detection of low‐abundant human leukocyte antigen (HLA) class‐I‐presented peptides from transformed cells. Human papillomavirus (HPV) was used as a model system, as the HPV oncoproteins E6 and E7 are attractive therapeutic vaccination targets and expressed in all transformed cells, but present at low abundance due to viral immune evasion mechanisms. The presented approach included preselection of target antigen‐derived peptides by in silico predictions and in vitro binding assays. The peptide purification process was tailored to minimize contaminants after immunoprecipitation of HLA‐peptide complexes, while keeping high isolation yields of low‐abundant target peptides. The subsequent targeted LC‐MS3 detection allowed for increased sensitivity, which resulted in successful detection of the known HLA‐A2‐restricted epitope E711–19 and ten additional E7‐derived peptides on the surface of HPV16‐transformed cells. T‐cell reactivity was shown for all the 11 detected peptides in ELISpot assays, which shows that detection by our approach has high predictive value for immunogenicity. The presented strategy is suitable for validating even low‐abundant candidate epitopes to be true immunotherapy targets.

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Section: Introductionmentioning

confidence: 99%

A Targeted LC‐MS Strategy for Low‐Abundant HLA Class‐I‐Presented Peptide Detection Identifies Novel Human Papillomavirus T‐Cell Epitopes

et al. 2018

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“…Despite widespread screening programs, cervical cancer remains frequent cancer among women worldwide, with the highest mortality rates in developing countries 1. Although human papillomavirus (HPV) vaccines are available, cervical cancer still causes a considerable amount of death because of the limited application of the vaccine.…”

Section: Introductionmentioning

confidence: 99%

INPP4B restrains cell proliferation and metastasis via regulation of the PI3K/AKT/SGK pathway

Chen

Sun

et al. 2018

J Cellular Molecular Medi

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Cervical cancer continues to be among the most frequent gynaecologic cancers worldwide. The phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT) pathway is constitutively activated in cervical cancer. Inositol polyphosphate 4‐phosphatase type II (INPP4B) is a phosphoinositide phosphatase and considered a negative regulatory factor of the PI3K/AKT pathway. INPP4B has diverse roles in various tumours, but its role in cervical cancer is largely unknown. In this study, we investigated the role of INPP4B in cervical cancer. Overexpression of INPP4B in HeLa, SiHa and C33a cells inhibited cell proliferation, metastasis and invasiveness in CCK‐8, colony formation, anchorage‐independent growth in soft agar and Transwell assay. INPP4B reduced the expression of some essential proteins in the PI3K/AKT/SGK3 pathway including p‐AKT, p‐SGK3, p‐mTOR, phospho‐p70S6K and PDK1. In addition, overexpression of INPP4B decreased xenograft tumour growth in nude mice. Loss of INPP4B protein expression was found in more than 60% of human cervical carcinoma samples. In conclusion, INPP4B impedes the proliferation and invasiveness of cervical cancer cells by inhibiting the activation of two downstream molecules of the PI3K pathway, AKT and SGK3. INPP4B acts as a tumour suppressor in cervical cancer cells.

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“…The focus is on HPV16, the most frequent and most carcinogenic type,12, 13 which is also the most difficult to control by vaccination8 due to its special propensity to persist. In a previous study,14 using idealized sexual contact structures, we have shown how HPV control through vaccination becomes more challenging in a population transitioning from a traditional to a gender‐equal sexual behavior.…”

Section: Introductionmentioning

confidence: 99%

Impacts of human papillomavirus vaccination for different populations: A modeling study

Baussano

Lazzarato

Ronco³

et al. 2018

Intl Journal of Cancer

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International variations in the prevalence of HPV infection derive from differences in sexual behaviors, which are also a key factor of the basic reproductive number (R0) of HPV infection in different populations. R 0 affects the strength of herd protection and hence the impact of a vaccination program. Similar vaccination programs may therefore generate different levels of impact depending upon the population's pre‐vaccination HPV prevalence. We used IARC's transmission model to estimate (i) the overall effectiveness of vaccination versus no vaccination in women aged 15–34 years measured as percent prevalence reduction (%PR) of HPV16 and (ii) the corresponding herd protection in populations with gender‐equal or traditional sexual behavior and with different levels of sexual activity, corresponding to pre‐vaccination HPV16 prevalence from 1 to 8% as observed worldwide. Between populations with different levels of gender‐equal sexual activity, the highest difference in %PR under girls‐only vaccination is observed at 40% coverage (91%PR vs. 48%PR for 1% and 8% pre‐vaccination prevalence, respectively). HPV16 elimination is obtained with 55 and 97% coverage, respectively. To achieve desirable levels of HPV16 prevalence after vaccination, different levels of coverage are required in populations with different levels of pre‐vaccination HPV16 prevalence, for example, in populations with gender‐equal sexual behavior a decrease to 1/1000 HPV16 from pre‐vaccination prevalence of 1 and 8% would require coverages of 37 and 96%, respectively. In traditional populations, corresponding coverages would need to be 28 and 93%, respectively. In conclusion, pre‐vaccination HPV prevalence strongly influences herd immunity and helps predict the overall effectiveness of HPV vaccination.

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Carcinogenic human papillomavirus infection

Cited by 716 publications

References 202 publications

A Targeted LC‐MS Strategy for Low‐Abundant HLA Class‐I‐Presented Peptide Detection Identifies Novel Human Papillomavirus T‐Cell Epitopes

A Targeted LC‐MS Strategy for Low‐Abundant HLA Class‐I‐Presented Peptide Detection Identifies Novel Human Papillomavirus T‐Cell Epitopes

INPP4B restrains cell proliferation and metastasis via regulation of the PI3K/AKT/SGK pathway

Impacts of human papillomavirus vaccination for different populations: A modeling study

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