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International Journal of Molecular... Nov 2022Biomarkers are crucial in oncology, from detection and monitoring to guiding management and predicting treatment outcomes. Histological assessment of tissue biopsies is... (Review)
Review
Biomarkers are crucial in oncology, from detection and monitoring to guiding management and predicting treatment outcomes. Histological assessment of tissue biopsies is currently the gold standard for oropharyngeal cancers, but is technically demanding, invasive, and expensive. This systematic review aims to review current markers that are detectable in biofluids, which offer promising non-invasive alternatives in oropharyngeal carcinomas (OPCs). A total of 174 clinical trials from the PubMed search engine in the last 5 years were identified and screened by 4 independent reviewers. From these, 38 eligible clinical trials were found and subsequently reviewed. The biomarkers involved, categorized by human papillomavirus (HPV)-status, were further divided according to molecular and cellular levels. Recent trials investigating biomarkers for both HPV-positive and HPV-negative OPCs have approaches from various levels and different biofluids including plasma, oropharyngeal swabs, and oral rinse. Promising candidates have been found to aid in detection, staging, and predicting prognosis, in addition to well-established factors including HPV-status, drinking and smoking status. These studies also emphasize the possibility of enhancing prediction results and increasing statistical significance by multivariate analyses. Liquid biopsies offer promising assistance in enhancing personalized medicine for cancer treatment, from lowering barriers towards early screening, to facilitating de-escalation of treatment. However, further research is needed, and the combination of liquid biopsies with pre-existing methods, including in vivo imaging and invasive techniques such as neck dissections, could also be explored in future trials.
Topics: Humans; Alphapapillomavirus; Papillomaviridae; Oropharyngeal Neoplasms; Biomarkers; Carcinoma
PubMed: 36430813
DOI: 10.3390/ijms232214336 -
International Journal of Molecular... Oct 2022Human papillomavirus type 16 (HPV-16) is a well-known etiological factor for cervical and oropharyngeal cancers. The E2 protein, the product of an early-transcribed gene... (Review)
Review
Human papillomavirus type 16 (HPV-16) is a well-known etiological factor for cervical and oropharyngeal cancers. The E2 protein, the product of an early-transcribed gene in HPV-16, is postulated to cause the death of cancerous cells via p53-dependent and p53-independent pathways. The main aim of the present systematic review was to study the HPV 16-E2 protein as an apoptosis-inducer agent. A thorough search of MEDLINE/PubMed, Science Direct, Scopus, and EBSCOhost databases was conducted for relevant studies on HPV AND apoptosis OR cell death where HPV 16-E2 was involved. The search identified 967 publications. Eleven records dated from 1 January 1997 to 16 February 2022 were found to meet the inclusion criteria and were eligible for data extraction and inclusion. All studies concluded that HPV 16-E2 was able to induce cell death in transfected cells. E2 proteins from the high-risk HPV-16 were able to induce apoptosis through different apoptotic pathways depending on the location of the expressed gene. However, the mechanism was still unclear, and further studies are warranted.
Topics: Humans; Female; Apoptosis Regulatory Proteins; Tumor Suppressor Protein p53; Oncogene Proteins, Viral; Human papillomavirus 16; Apoptosis; Papillomavirus Infections; Oropharyngeal Neoplasms; Uterine Cervical Neoplasms; Papillomaviridae
PubMed: 36293403
DOI: 10.3390/ijms232012554 -
Journal For Immunotherapy of Cancer Oct 2022The addition of cetuximab significantly increased the antitumor effect of programmed cell death protein 1 (PD-1) inhibitors in recurrent or metastatic head and neck... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The addition of cetuximab significantly increased the antitumor effect of programmed cell death protein 1 (PD-1) inhibitors in recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). However, preliminary analyses suggested that human papillomavirus (HPV)-positive disease benefited less than HPV-negative disease. Therefore, we conducted a meta-analysis to assess whether the efficacy of the combination therapy varied according to HPV status in HNSCC.
METHODS
We identified clinical trials of patients with recurrent or metastatic HNSCC who received PD-1 inhibitor monotherapy or the combination therapy of cetuximab plus a PD-1 inhibitor. The participants were divided into four groups based on the type of therapy (combination vs monotherapy) and HPV status (positive vs negative). We focused on three comparisons (monotherapy vs combination therapy by HPV status and HPV-positive vs HPV-negative disease in combination therapy). The primary and secondary endpoints were objective response rate (ORR) and 1-year overall survival (OS) rate, respectively. The ORR and 1-year OS rate were pooled using random-effects models for each group and were compared for the different comparisons.
RESULTS
Overall, 802 patients from seven trials were eligible for the ORR assessment; of which, 684 patients received PD-1 inhibitor monotherapy and 118 patients underwent the combination therapy. Compared with PD-1 inhibitor monotherapy, the addition of cetuximab improved the ORR in HPV-negative disease (pooled ORR in monotherapy vs combination therapy: 15% vs 46%, p<0.001) but not in HPV-positive disease (17% vs 18%, p=0.686). The efficacy of adding cetuximab was consistent for the 1-year OS rate in HPV-negative disease (pooled 1-year OS rate in monotherapy vs combination therapy: 36% vs 59%, p<0.001) and in HPV-positive disease (40% vs 55%, p=0.252). After the combination therapy, HPV-positive disease had a significantly lower ORR than HPV-negative disease (odds ratio: 0.29, p=0.004), but no differences were shown in the 1-year OS rate.
CONCLUSIONS
Our meta-analysis suggests that the addition of cetuximab to a PD-1 inhibitor is more effective compared with PD-1 inhibitor monotherapy only in patients with HPV-negative HNSCC. Despite the retrospective nature of this meta-analysis, these findings should help in designing relevant clinical trials rationally.
Topics: Cetuximab; Head and Neck Neoplasms; Humans; Immune Checkpoint Inhibitors; Papillomaviridae; Papillomavirus Infections; Programmed Cell Death 1 Receptor; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck
PubMed: 36253001
DOI: 10.1136/jitc-2022-005158 -
Journal of Medical Virology Jan 2023Bladder cancer (BCa) is the 10th most common type of cancer worldwide, and human papillomavirus (HPV) is the most common sexually transmitted infection. However, the... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Bladder cancer (BCa) is the 10th most common type of cancer worldwide, and human papillomavirus (HPV) is the most common sexually transmitted infection. However, the relationship between HPV infection and the risk of BCa is still controversial and inconclusive.
METHODS
This systematic review and meta-analysis were conducted following the PRISMA 2020 reporting guideline. This study searched four bibliographic databases with no language limitation. The databases included PubMed (Medline), EMBASE, Cochrane Library, and Web of Science. Studies evaluating the interaction between HPV infection and the risk of BCa from inception through May 21, 2022, were identified and used in this study. This study estimated the overall and type-specific HPV prevalence and 95% confidence intervals (95% CI) using Random Effects models and Fixed Effects models. In addition, this study also calculated the pooled odds ratio and pooled risk ratio with 95% CI to assess the effect of HPV infection on the risk and prognosis of bladder cancer. Two-sample mendelian randomization (MR) study using genetic variants associated with HPV E7 protein as instrumental variables were also conducted.
RESULTS
This study retrieved 80 articles from the four bibliographic databases. Of the total, 27 were case-control studies, and 53 were cross-sectional studies. The results showed that the prevalence of HPV was 16% (95% CI: 11%-21%) among the BCa patients, most of which were HPV-16 (5.99% [95% CI: 3.03%-9.69%]) and HPV-18 (3.68% [95% CI: 1.72%-6.16%]) subtypes. However, the study found that the prevalence varied by region, detection method, BCa histological type, and sample source. A significantly increased risk of BCa was shown for the positivity of overall HPV (odds ratio [OR], 3.35 [95% CI: 1.75-6.43]), which was also influenced by study region, detection method, histological type, and sample source. In addition, the study found that HPV infection was significantly associated with the progression of BCa (RR, 1.73 [95% CI: 1.39-2.15]). The two-sample MR analysis found that both HPV 16 and 18 E7 protein exposure increased the risk of BCa (HPV 16 E7 protein: IVW OR per unit increase in protein level = 1.0004 [95% CI: 1.0002-1.0006]; p = 0.0011; HPV 18 E7 protein: IVW OR per unit increase in protein level = 1.0003 [95% CI: 1.0001-1.0005]; p = 0.0089).
CONCLUSION
In conclusion, HPV may play a role in bladder carcinogenesis and contribute to a worse prognosis for patients with BCa. Therefore, it is necessary for people, especially men, to get vaccinated for HPV vaccination to prevent bladder cancer.
Topics: Male; Humans; Papillomavirus Infections; Human Papillomavirus Viruses; Mendelian Randomization Analysis; Papillomaviridae; Human papillomavirus 18; Urinary Bladder Neoplasms
PubMed: 36226344
DOI: 10.1002/jmv.28208 -
BMJ Sexual & Reproductive Health Oct 2022To provide insights into women's attitudes towards a human papillomavirus (HPV)-based cervical cancer screening strategy. (Review)
Review
OBJECTIVE
To provide insights into women's attitudes towards a human papillomavirus (HPV)-based cervical cancer screening strategy.
DATA SOURCES
Medline, Web of Science Core Collection, Cochrane Library, PsycINFO, CINAHL and ClinicalTrials.gov were systematically searched for published and ongoing studies (last search conducted in August 2021).
METHODS OF STUDY SELECTION
The search identified 3162 references. Qualitative and quantitative studies dealing with women's attitudes towards, and acceptance of, an HPV-based cervical cancer screening strategy in Western healthcare systems were included. For data analysis, thematic analysis was used and synthesised findings were presented descriptively.
TABULATION, INTEGRATION, AND RESULTS
Twelve studies (including 9928 women) from USA, Canada, UK and Australia met the inclusion criteria. Women's attitudes towards HPV-based screening strategies were mainly affected by the understanding of (i) the personal risk of an HPV infection, (ii) the implication of a positive finding and (iii) the overall screening purpose. Women who considered their personal risk of HPV to be low and women who feared negative implications of a positive finding were more likely to express negative attitudes, whereas positive attitudes were particularly expressed by women understanding the screening purpose. Overall acceptance of an HPV-based screening strategy ranged between 13% and 84%.
CONCLUSION
This systematic review provides insights into the attitudes towards HPV-based cervical cancer screening and its acceptability based on studies conducted with women from USA, Canada, UK and Australia. This knowledge is essential for the development of education and information strategies to support the implementation of HPV-based cervical cancer screening.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (CRD42020178957).
Topics: Alphapapillomavirus; Early Detection of Cancer; Female; Health Knowledge, Attitudes, Practice; Humans; Papillomaviridae; Papillomavirus Infections; Uterine Cervical Neoplasms
PubMed: 36223918
DOI: 10.1136/bmjsrh-2022-201515 -
PloS One 2022Human papillomavirus is one of the most important causes of cervical cancer. Participating in an HPV test and receiving an HPV diagnosis can create questions about the...
OBJECTIVES
Human papillomavirus is one of the most important causes of cervical cancer. Participating in an HPV test and receiving an HPV diagnosis can create questions about the needs and preferences. The present systematic review was conducted to determine the reproductive health needs of women with HPV.
METHODS
We searched PubMed, Scopus, Web of Science, Google Scholar and Magiran, SID and Iranmedex. Without language restrictions and time constraints. We also searched the grey literature and carried out forward/backward citation searches.
RESULTS
In the first, 1056 articles were retrieved, and, after removing them, 13 articles published were entered. The studies were qualitative (N = 9), quantitative (N = 3), and one was unclear. Most qualitative studies collected data using individual interviews (N = 7), two qualitative studies, narratives of HPV patients from a website of patient experiences and questions. Women wanted further information on different HPV viral types, transmission, implications for sexual partners, prevalence, latency and regression of HPV, their management options and the implications of infection for cancer risk and fertility. Women's experience of searching the Internet for further information about HPV was reported as difficult, anxiety provoking and contributing to the stigma of the infection because information was often located in the context of other sexually transmitted infections, with multiple sexual partners highlighted as a risk factor for infection.
CONCLUSION
Surveys showed that the majority of women had unanswered questions about their HPV test results. The information that women thought was helpful in interpreting their test results included having a high-risk type of HPV, and cancer survival statistics for the virus. Women also needed information about sexual transmission, how HPV tested positive in a long-term relationship, and the potential consequences for their partners and the risk of re-infection. Younger women had questions about whether HPV could affect fertility.
Topics: Alphapapillomavirus; Female; Humans; Papillomaviridae; Papillomavirus Infections; Reproductive Health; Uterine Cervical Neoplasms
PubMed: 36095006
DOI: 10.1371/journal.pone.0266819 -
Vaccine Sep 2022National HPV vaccination coverage in Japan is less than one percent of the eligible population and cervical cancer incidence and mortality are increasing. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
National HPV vaccination coverage in Japan is less than one percent of the eligible population and cervical cancer incidence and mortality are increasing. This systematic review and meta-analysis aimed to provide a comprehensive estimate of HPV genotype prevalence for Japan.
METHODS
English and Japanese databases were searched to March 2021 for research reporting HPV genotypes in cytology and histology samples from Japanese women. Summary estimates were calculated by disease stage from cytology only assessment - Normal, ASCUS, LSIL, HSIL and from histological assessment - CIN1, CIN2, CIN3/AIS, ICC (ICC-SCC, and ICC-ADC), and other. A random-effects meta-analysis was used to calculate summary prevalence estimates of any-HPV, high-risk (HR) and low-risk (LR) vaccine types, and vaccine genotypes (bivalent, quadrivalent, or nonavalent). This study was registered with PROSPERO: CRD42018117596.
RESULTS
A total of 57759 women with normal cytology, 1766 ASCUS, 3764 LSIL, 2017 HSIL, 3130 CIN1, 1219 CIN2, 869 CIN3/AIS, and 4306 ICC (which included 1032 ICC-SCC, and 638 ICC-ADC) were tested for HPV. The summary estimate of any-HPV genotype in women with normal cytology was 15·6% (95% CI: 12·3-19·4) and in invasive cervical cancer (ICC) was 85·6% (80·7-89·8). The prevalence of HR-HPV was 86·0% (95% CI: 73·9-94·9) for cytological cases of HSIL, 76·9% (52·1-94·7) for histological cases of CIN3/AIS, and 75·7% (68·0-82·6) for ICC. In women with ICC, the summary prevalence of bivalent vaccine genotypes was 58·5% (95% CI: 52·1-64·9), for quadrivalent genotypes was 58·6% (52·2-64·9) and for nonavalent genotypes was 71·5% (64·9-77·6), and of ICC cases that were HPV positive over 90% of infections are nonavalent vaccine preventable. There was considerable heterogeneity in all HPV summary estimates and for ICC, this heterogeneity was not explained by variability in study design, sample type, HPV assay type, or HPV DNA detection method, although studies published in the 1990s had lower prevalence estimates of any-HPV and HR HPV genotypes.
INTERPRETATIONS
HPV prevalence is high among Japanese women. The nonavalent vaccine is likely to have the greatest impact on reducing cervical cancer incidence and mortality in Japan.
Topics: Age Distribution; Alphapapillomavirus; Atypical Squamous Cells of the Cervix; DNA; Female; Genotype; Humans; Japan; Papillomaviridae; Papillomavirus Infections; Prevalence; Uterine Cervical Neoplasms; Vaccines, Combined; Uterine Cervical Dysplasia
PubMed: 36085257
DOI: 10.1016/j.vaccine.2022.07.052 -
Journal of the European Academy of... Jan 2023Keratinocyte skin cancers are the most frequent malignancy, accounting for approximately 30% of all cancers. Although beta genus HPV are the main etiologic agents for... (Review)
Review
Keratinocyte skin cancers are the most frequent malignancy, accounting for approximately 30% of all cancers. Although beta genus HPV are the main etiologic agents for squamous cell carcinoma development in patients with epidermodysplasia verruciformis and organ transplant recipients, their role in non-melanoma skin cancer (NMSC) progression in the general population remains controversial. The aim of our review is to summarize current scientific data and to systematically analyse evidence regarding the role of HPV in keratinocyte skin cancers. A total of 2284 patients were included, of which 724 with actinic keratoses, 290 with Bowen's disease, 949 with cutaneous squamous cell carcinomas and 321 with keratoacanthomas. In the case of actinic keratoses, the majority were positive for beta (n = 372, 58.49%) and gamma HPV (n = 256, 40.25%) and only a few (n = 6, 0.94%) were positive for alpha subtypes. Similarly, most of the cutaneous squamous cell carcinomas were positive for beta (n = 248, 55.98%) and gamma HPV (n = 172, 33.82%) and 23 cases (2.42%) were positive for alpha subtypes. Bowen's disease lesions were mostly positive for beta (n = 43, 55.84%) and alpha HPV (n = 30, 38.96%), in contrast to the gamma genus (n = 4, 5.19%). Keratoacanthomas showed a high distribution among beta genus (n = 79, 50.31%) and an equal proportion between alpha (n = 39, 24.84%) and gamma (n = 39, 24.84%) genera. Studies published so far identifying HPV in keratinocyte skin cancers reflect the difference in detection methods rather than a type-specific tendency towards either actinic keratoses, Bowen's disease, squamous cell carcinoma or keratoacanthoma. On the other hand, recent evidence regarding the role of HPV vaccination in patients with non-melanoma skin cancer brings into perspective the idea of a beta-HPV vaccine or a combined alpha and beta-HPV vaccine that could be used as an adjuvant treatment measure in patients with recalcitrant non-melanoma skin cancer.
Topics: Humans; Bowen's Disease; Keratoacanthoma; Keratosis, Actinic; Papillomavirus Infections; Papillomaviridae; DNA, Viral; Skin Neoplasms; Carcinoma, Squamous Cell; Keratinocytes; Papillomavirus Vaccines
PubMed: 36000380
DOI: 10.1111/jdv.18548 -
CA: a Cancer Journal For Clinicians Nov 2022Human papillomavirus (HPV) is currently linked to almost 35,000 new cases of cancer in women and men each year in the United States. Gardasil-9 (Merck & Company),...
Human papillomavirus (HPV) is currently linked to almost 35,000 new cases of cancer in women and men each year in the United States. Gardasil-9 (Merck & Company), the only HPV vaccine now available in the United States, is nearly 100% effective at preventing precancers caused by oncogenic HPV types. In the United States, however, only about one half of adolescents are up to date with HPV vaccination. It is well known that health care clinicians' recommendations play a significant role in parents' decisions regarding HPV vaccination. A growing body of literature examines specific communication strategies for promoting uptake of the HPV vaccine. A comprehensive review of the evidence for each of these strategies is needed. The authors searched the PubMed, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, and Web of Science Complete databases for original articles with a defined clinician communication strategy and an outcome of HPV vaccine uptake or intention to vaccinate (PROSPERO registry no. CRD42020107602). In total, 46 studies were included. The authors identified two main strategies with strong evidence supporting their positive impact on vaccine uptake: strong recommendation and presumptive recommendation. Determinations about a causal relationship were limited by the small numbers of randomized controlled trials. There is also opportunity for more research to determine the effects of motivational interviewing and cancer-prevention messaging.
Topics: Adolescent; Male; Female; Humans; United States; Papillomavirus Infections; Papillomavirus Vaccines; Vaccination; Alphapapillomavirus; Communication; Parents; Neoplasms
PubMed: 35969145
DOI: 10.3322/caac.21753 -
Vaccine Sep 2022Human papillomavirus (HPV) vaccines were first licensed as a three-dose series. Two doses are now widely recommended in some age groups; there are data suggesting high... (Review)
Review
BACKGROUND
Human papillomavirus (HPV) vaccines were first licensed as a three-dose series. Two doses are now widely recommended in some age groups; there are data suggesting high efficacy with one dose. We updated a systematic literature review of HPV vaccine effectiveness by number of doses in observational studies.
METHODS
We searched Medline and Embase databases from January 1, 2007, through September 29, 2021. Data were extracted and summarized in a narrative synthesis. We also conducted quality assessments for bias due to selection, information, and confounding.
RESULTS
Overall, 35 studies were included; all except one were conducted within the context of a recommended three-dose schedule. Evaluations were in countries that used bivalent HPV vaccine (seven), quadrivalent HPV vaccine (27) or both (one). Nine evaluated effectiveness against HPV infection, ten anogenital warts, and 16 cervical abnormalities. All studies were judged to have moderate or serious risk of bias. The biases rated as serious would likely result in lower effectiveness with fewer doses. Investigators attempted to control for or stratify by potentially important variables, such as age at vaccination. Eight studies evaluated impact of buffer periods (lag time) for case counting and 10 evaluated different intervals between doses for two-dose vaccine recipients. Studies that stratified by vaccination age found higher effectiveness with younger age at vaccination, although differences were not all formally tested. Most studies found highest estimates of effectiveness with three doses; significant effectiveness was found among 28/29 studies that evaluated three doses, 19/29 that evaluated two doses, and 18/30 that evaluated one dose. Some studies that adjusted or stratified analyses by age at vaccination found similar effectiveness with three, two and one doses.
CONCLUSION
Observational studies of HPV vaccine effectiveness have many biases. Studies examining persons vaccinated prior to sexual activity and using methods to reduce sources of bias are needed for valid effectiveness estimates.
Topics: Alphapapillomavirus; Female; Humans; Immunization Programs; Papillomavirus Infections; Papillomavirus Vaccines; Uterine Cervical Neoplasms; Vaccination; Vaccine Efficacy
PubMed: 35965239
DOI: 10.1016/j.vaccine.2022.06.065