Role Of Human Papillomavirus Infection Research Articles

The BICD2 dynein cargo adaptor binds to the HPV16 L2 capsid protein and promotes HPV infection.

During entry, human papillomavirus (HPV) traffics from the endosome to the trans Golgi network (TGN) and Golgi and then the nucleus to cause infection. Although dynein is thought to play a role in HPV infection, how this host motor recruits the virus to support infection and which entry step(s) requires dynein are unclear. Here we show that the dynein cargo adaptor BICD2 binds to the HPV L2 capsid protein during entry, recruiting HPV to dynein for transport of the virus along the endosome-TGN/Golgi axis to promote infection. In the absence of BICD2 function, HPV accumulates in the endosome and TGN and infection is inhibited. Cell-based and in vitro binding studies identified a short segment near the C-terminus of L2 that can directly interact with BICD2. Our results reveal the molecular basis by which the dynein motor captures HPV to promote infection and identify this virus as a novel cargo of the BICD2 dynein adaptor.

The HPV viral regulatory mechanism of TLRs and the related treatments for HPV-associated cancers.

Infection with human papillomavirus (HPV) typically leads to cervical cancer, skin related cancers and many other tumors. HPV is mainly responsible for evading immune tumor monitoring in HPV related cancers. Toll like receptors (TLRs) are particular pattern recognition molecules. When the body is facing immune danger, it can lead to innate and direct adaptive immunity. TLR plays an important role in initiating antiviral immune responses. HPV can affect the expression level of TLR and interfere with TLR related signaling pathways, resulting in sustained viral infection and even carcinogenesis. This paper introduces the HPV virus and HPV related cancers. We discussed the present comprehension of TLR, its expression and signaling, as well as its role in HPV infection. We also provided a detailed introduction to immunotherapy methods for HPV related diseases based on TLR agonists. This will provide insights into methods that support the therapeutic method of HPV related conditions with TLR agonists.

Microbiome markers in HPV-positive and HPV-negative women of reproductive age with ASCUS and SIL determined by V4 region of 16S rRNA gene sequencing.

Human papilloma virus (HPV) is the most common sexually transmitted infection worldwide. Cervicovaginal microbiota plays an important role in HPV infection and is associated with the development of squamous intraepithelial lesions (SIL). The natural history of cervical cancer involves reversible changes in the cervical tissue from a normal state, in which no neoplastic changes are detected in the squamous epithelium, to varying states of cellular abnormalities that ultimately lead to cervical cancer. Low-grade SIL (LSIL), like another cytological category - atypical squamous cells of undetermined significance (ASCUS), may progress to high-grade SIL (HSIL) and invasive cervical cancer or may regress to a normal state. In this work, we studied cervical canal microbiome in 165 HPV-positive and HPV-negative women of a reproductive age with ASCUS [HPV(+) n = 29; HPV(-) n = 11], LSIL [HPV(+) n = 32; HPV(-) n = 25], HSIL [HPV(+) n = 46], and the control group with negative for intraepithelial lesion malignancy (NILM) [HPV(-) n = 22]. HPV16 is the most prevalent HPV type. We have not found any differences between diversity in studied groups, but several genus [like Prevotella (p-value = 0.026), Gardnerella (p-value = 0.003), Fannyhessea (p-value = 0.024)] more often occurred in HSIL group compared by NILM or LSIL regardless of HPV. We have found statistically significant difference in occurrence or proportion of bacterial genus in studied groups. We also identified that increasing of the ratio of Lactobacillus iners or age of patient lead to higher chance to HSIL, while increasing of the ratio of Lactobacillus crispatus lead to higher chance to LSIL. Patients with a moderate dysbiosis equally often had either of three types of vaginal microbial communities (CST, Community State Type) with the prevalence of Lactobacillus crispatus (CST I), Lactobacillus gasseri (CST II), and Lactobacillus iners (CST III); whereas severe dysbiosis is linked with CST IV involving the microorganisms genera associated with bacterial vaginosis and aerobic vaginitis: Gardnerella, Fannyhessea, Dialister, Sneathia, Anaerococcus, Megasphaera, Prevotella, Finegoldia, Peptoniphilus, Porphyromonas, Parvimonas, and Streptococcus.

Human Papillomavirus Infections and the Role Played by Cervical and Cervico-Vaginal Microbiota-Evidence from Next-Generation Sequencing Studies.

This comprehensive review encompasses studies examining changes in the cervical and cervico-vaginal microbiota (CM and CVM) in relation to human papillomavirus (HPV) using next-generation sequencing (NGS) technology. HPV infection remains a prominent global health concern, with a spectrum of manifestations, from benign lesions to life-threatening cervical cancers. The CM and CVM, a unique collection of microorganisms inhabiting the cervix/vagina, has emerged as a critical player in cervical health. Recent research has indicated that disruptions in the CM and CVM, characterized by a decrease in Lactobacillus and the overgrowth of other bacteria, might increase the risk of HPV persistence and the progression of cervical abnormalities. This alteration in the CM or CVM has been linked to a higher likelihood of HPV infection and cervical dysplasia. NGS technology has revolutionized the study of the cervical microbiome, providing insights into microbial diversity, dynamics, and taxonomic classifications. Bacterial 16S rRNA gene sequencing, has proven invaluable in characterizing the cervical microbiome, shedding light on its role in HPV infections and paving the way for more tailored strategies to combat cervical diseases. NGS-based studies offer personalized insights into an individual's cervical microbiome. This knowledge holds promise for the development of novel diagnostic tools, targeted therapies, and preventive interventions for cervix-related conditions, including cervical cancer.

Vaginal microecology and its role in human papillomavirus infection and human papillomavirus associated cervical lesions.

The vaginal microecology comprises the vaginal microbiome, immune microenvironment, vaginal anatomy, and the cervicovaginal fluid, which is rich in metabolites, enzymes, and cytokines. Investigating its role in the female reproductive system holds paramount significance. The advent of next-generation sequencing enabled a more profound investigation into the structure of the vaginal microbial community in relation to the female reproductive system. Human papillomavirus infection is prevalent among women of reproductive age, and persistent oncogenic HPV infection is widely recognized as a factor associated with cervical cancer. Extensive previous research has demonstrated that dysbiosis of vaginal microbiota characterized by a reduction in Lactobacillus species, heightens susceptivity to HPV infection, consequently contributing to persistent HPV infection and the progression of cervical lesion. Likewise, HPV infection can exacerbate dysbiosis. This review aims to provide a comprehensive summary of current literatures and to elucidate potential mechanisms underlying the interaction between vaginal microecology and HPV infection, with the intention of offering valuable insights for future clinical interventions.

Genetic Modulation of HPV Infection and Cervical Lesions: Role of Oxidative Stress-Related Genes.

Human papillomavirus (HPV) infection is a necessary but not sufficient factor for the development of invasive cervical cancer (ICC) and high-grade intraepithelial lesion (HSIL). Oxidative stress is known to play a crucial role in HPV infection and carcinogenesis. In this study, we comprehensively investigate the modulation of HPV infection, HSIL and ICC, and ICC through an exploration of oxidative stress-related genes: CβS, MTHFR, NOS3, ACE1, CYBA, HAP, ACP1, GSTT1, GSTM1, and CYP1A1. Notably, the ACE1 gene emerges as a prominent factor with the presence of the I allele offering protection against HPV infection. The association of NOS3 with HPV infection is perceived with the 4a allele showing a protective effect. The presence of the GSTT1 null mutant correlates with increased susceptibility to HPV infection, HSIL and ICC, and ICC. This study also uncovers intriguing epistatic interactions among some of the genes that further accentuate their roles in disease modulation. Indeed, the epistatic interactions between the BB genotype (ACP1) and DD genotype (ECA1) were shown to increase the risk of HPV infection, and the interaction between BB (ACP1) and 0.0 (GSTT1) was associated with HPV infection and cervical lesions. These findings underscore the pivotal role of four oxidative stress-related genes in HPV-associated cervical lesions and cancer development, enriching our clinical understanding of the genetic influences on disease manifestation. The awareness of these genetic variations holds potential clinical implications.

Role of Ureaplasma urealyticum and Ureaplasma parvum as Risk Factors for Cervical Dysplasia with Human Papillomavirus

Human papillomavirus (HPV) can be transmitted sexually and causes cervical malignancies in women. Among the risk factors, sexually transmitted infections (STIs) caused by bacteria have raised concerns because they are asymptomatic and persistent and can increase the risk of HPV infection. This study assessed the correlation among Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, and Mycoplasma hominis infections towards abnormal cervical cells positive for HPV. Seventy outpatients at the Colposcopy Outpatient Clinic, Dr. Cipto Mangunkusumo Hospital in Jakarta, Indonesia, were enrolled in this cross-sectional study. Viruses and bacteria were detected using polymerase chain reaction and compared with liquid-based cytology results for cervical cytology. Of the 70 patients, 24 (34.28%) showed abnormal cervical cytology. Among those with abnormal cervical cytology, C.trachomatis was reported in 1 patient (4.2%), M.hominis in 6 patients (25%), U.urealyticum in 13 patients (54.2%), and U.parvum in 10 patients (41.7%). Statistical analysis demonstrated an association between U.urealyticum and U.parvum infections and HPV infection (U.urealyticum p = 0.012; U.parvum p = 0.022). U.urealyticum and U.parvum were more prevalent than C.trachomatis and M.hominis in HPV-positive women, suggesting their role in HPV infection.

The Role of Human Papilloma Virus in the Pathogenesis of Sinonasal Inverted Papilloma; A Metanalytical Study

Abstract Background Sinonasal inverted papilloma (SNIP) is a benign and relatively rare tumor of the nasal cavity and paranasal sinuses, most commonly originates from the lateral nasal wall or maxillary sinus from the schneiderian sinonasal epithelium. There is a male predominance with a male-to-female ratio of 3.4:1. Sinonasal Squamous Cell Carcinoma (SCC) associated with IP has an incidence of approx. 0.38 cases/million persons/year. Patients with carcinoma in IP are older than those IP patients without carcinoma. Some authors assume an influence of Human Papilloma Virus (HPV) subtyping. Transcripts of HPV DNA were found in malignant IP. Objective To perform a meta-analytical study to determine the relationship between human papilloma virus and the occurrence of sinonasal inverted papilloma. Patients and Methods The review will be restricted to RCTs, clinical trials, and comparative studies, either prospective or retrospective, which studied the outcome of Negative HPV group versus Positive HPV group of patients. Data Sources Medline databases (PubMed, Medscape, ScienceDirect. EMF-Portal) and all materials available in the Internet till 2021. Data Extraction If the studies did not fulfill the inclusion criteria, they were excluded. Study quality assessment included whether ethical approval was gained, eligibility criteria specified, appropriate controls, and adequate information and defined assessment measures. Results In our study HPV positive cases were (23.6%) (107/ 452) among SNIP patients. Malignant SNIP rate was (10.8%) (49/ 452). HPV positive cases among malignant SNIP patients was (51.02%) (25/49). Conclusion In this meta-analytical study HPV positive cases were (23.6%) (107/ 452) among SNIP patients. Malignant SNIP rate was (10.8%) (49/ 452). Though the etiology of SNIP remains controversial, the studies reviewed in this study indicate a role for HPV infection. Further studies in the future regarding the impact of other risk factors on the occurrence of SNIP would be of value, these factors include angiogenic factors, environmental factors, genetic, viral and chronic sinonasal inflammation.

TIME Is Ticking for Cervical Cancer.

Cervical cancer (CC) is a major health problem among reproductive-age females and comprises a leading cause of cancer-related deaths. Human papillomavirus (HPV) is the major risk factor associated with CC incidence. However, lifestyle is also a critical factor in CC pathogenesis. Despite HPV vaccination introduction, the incidence of CC is increasing worldwide. Therefore, it becomes critical to understand the CC tumor immune microenvironment (TIME) to develop immune cell-based vaccination and immunotherapeutic approaches. The current article discusses the immune environment in the normal cervix of adult females and its role in HPV infection. The subsequent sections discuss the alteration of different immune cells comprising CC TIME and their targeting as future therapeutic approaches.

Using focus groups to plan culturally acceptable primary cervical cancer screening in Grenada, West Indies.

To document Grenadian women's knowledge about cervical cancer and human papillomavirus (HPV) infection, as well as their attitudes towards primary cervical cancer screening methods. In this qualitative study, we used focus groups in Grenada to gather information concerning women's knowledge about, attitudes towards and perceptions of screening for cervical cancer and general knowledge about HPV. Ten focus groups comprising 73 participants representing 5 of the 6 parishes in Grenada were conducted with women aged 19-59. Participants were asked about pelvic exams, Pap smears, HPV, reasons for seeking or avoiding cervical cancer screening and how different modalities of testing might affect their decision-making. Responses were then coded and organized into common themes. While many respondents had heard of HPV, far fewer knew about its causative role in cervical cancer, how to prevent HPV infection or testing for the high-risk HPV types that cause almost all cases of cervical cancer. Many participants were aware that cervical cancer screening was beneficial, but numerous barriers to obtaining that screening were noted, including concerns about privacy and stigma, potential discomfort, and the cost and inconvenience involved. Our findings have implications for future cervical cancer screening efforts in Grenada. Central to these efforts should be a focus on educating Grenadians about the role of HPV infection in cervical cancer and the importance of early detection through screening. In addition, addressing issues of stigma and privacy are key to eliminating cervical cancer in Grenada.

Maternal human papillomavirus infection during pregnancy and preterm delivery, a mother-child cohort study in Norway and Sweden.

Human papillomavirus (HPV) infection is common in women of reproductive age. Infection and inflammation are leading causes for preterm delivery (PTD), but the role of HPV infection in PTD and prelabor rupture of membranes (PROM) is unclear. We aimed to explore whether HPV infection during pregnancy in general, and high-risk-HPV (HR-HPV) infection specifically, increased the risk of PTD, preterm prelabor rupture of membranes (PPROM), PROM at term, and/or chorioamnionitis. In pregnant women, who were participating in a prospective multicenter cohort study from a general population in Norway and Sweden (PreventADALL, ClinicalTrials.gov NCT02449850), HPV DNA was analyzed in available urine samples at mid-gestation (16-22 weeks) and at delivery, and in the placenta after delivery with Seegene Anyplex II HPV28 PCR assay. The risk of PTD, PPROM, PROM, and chorioamnionitis was analyzed using unadjusted and adjusted logistic regression analyses for any 28 HPV genotypes, including 12 HR-HPV genotypes, compared with HPV-negative women. Further, subgroups of HPV (low-risk/possibly HR-HPV, HR-HPV-non-16 and HR-HPV-16), persistence of HR-HPV from mid-gestation to delivery, HR-HPV-viral load, and presence of multiple HPV infections were analyzed for the obstetric outcomes. Samples for HPV analyses were available from 950 women with singleton pregnancies (mean age 32 years) at mid-gestation and in 753 also at delivery. At mid-gestation, 40% of women were positive for any HPV and 24% for HR-HPV. Of the 950 included women, 23 had PTD (2.4%), nine had PPROM (0.9%), and six had chorioamnionitis (0.6%). Of the term pregnancies, 25% involved PROM. The frequency of PTD was higher in HR-HPV-positive women (8/231, 3.5%) than in HPV-negative women (13/573, 2.3%) at mid-gestation, but the association was not statistically significant (odds ratio 1.55; 95% confidence interval 0.63-3.78). Neither any HPV nor subgroups of HPV at mid-gestation or delivery, nor persistence of HR-HPV was significantly associated with increased risk for PTD, PPROM, PROM, or chorioamnionitis. No HPV DNA was detected in placentas of women with PTD, PPROM or chorioamnionitis. HPV infection during pregnancy was not significantly associated with increased risk for PTD, PPROM, PROM, or chorioamnionitis among women from a general population with a low incidence of adverse obstetric outcomes.

Role of human papillomavirus infection in the development of oral leukoplakia and oral squamous cell carcinoma

BACKGROUND: The annual global oral cancer morbidity is more than 650,000 cases. Between 2007 and 2017 in the Russian Federation, the absolute number of first-ever diagnosed oral cavity malignant neoplasms is constantly increasing. According to many authors, oral squamous cell carcinoma is associated with pre-existing leukoplakia. This disease is the most common and prone to malignant precancerous oral mucosa disease. Human papillomaviruses (HPV) are crucial players in this process. However, the relationship between HPV infection in leukoplakia and oral squamous cell carcinoma remains unclear.
 AIM: To establish the HPV role in the development of leukoplakia and squamous cell carcinoma of the oral mucosa.
 MATERIAL AND METHODS: The study included 39 patients with verified various forms of oral leukoplakia and oral squamous cell carcinomas. The squamous cell carcinoma group included 19 patients. The oral leukoplakia group is consisted of 20 patients. The control group of healthy volunteers is represented by 22 patients with clinically healthy oral mucosa. HPV deoxyribonucleic acid (DNA) was detected and quantified in clinical materials by polymerase chain reaction with hybridization-fluorescence detection AmpliSense HPV HRS screen-titer-FL for HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 and AmpliSense HPV 6/11-FL for HPV types 6 and 11.
 RESULTS: HPV types 6 and 11 DNA were isolated in three cases with insignificant clinical disease from 19 samples taken from patients with oral squamous cell carcinoma. In groups of leukoplakia and healthy volunteers, no high oncological risk was identified. Despite a HPV-positive expression in squamous cell carcinoma samples is detected, no significant difference was found between the squamous cell carcinoma group and control group (p=0.09).
 CONCLUSION: No significant association was noted between HPV and oral squamous cell carcinoma; however, a low carcinogenic-risk HPV was detected in 15.7% of carcinoma samples. No HPV contamination was detected in patients with leukoplakia and healthy groups.

An overview of the general characteristics, pathogenicity, transmission, and diagnosis of human papilloma virus (HPV)

Mucous membrane infections are brought on by the double-standard DNA virus known as human papillomavirus (HPV). Cervix cell alterations are caused by a sexually transmitted illness. E6 and E7 oncogenes play a critical role in HPV infection. Finding these genes to identify HPV strains, particularly the HPV16 strain, will have a significant impact due to its exceptional sensitivity, the dielectric electrochemical biosensor stands out among other pathogen detection methods. Recent evidence suggests that E6 and E7 are also important in inhibiting the innate immune response of the host cell to HPV. Viral replication is mediated by the E1 and E2 proteins in conjunction with other biological stimuli. E2 has also been linked to viral and cellular transcriptional regulation. Despite decades of research, the function of other viral proteins still remains unclear. Therefore, analysis of Human Papilloma Virus (HPV) characteristics, pathogenicity, transmission and diagnosis were reviewed. We concluded that we now have the tools and methodologies necessary to answer this critical question about viral tropism. The discovery of efficient treatments to cure or prevent HPV-induced illness is just as vital as studying the underlying mechanisms of HPV pathogenesis. The identification of drugs specifically to treat HPV infection has not been highly successful due to the complexities of the HPV life cycle and the limited number of enzymatic activities identified for HPV proteins. The development of drug treatments for existing HPV disease is an important undertaking that deserves further attention. In this regard, the development of therapeutic vaccines and self-protection are promising area of investigation and needs to be further supported.

Genital Cytokines in HIV/Human Papillomavirus Co-Infection: A Systematic Review.

Cervical cancer is the fourth cancer in incidence and the third in mortality among women worldwide. Women living with HIV have a significantly increased risk of cervical cancer. The immune response of the host is crucial to determine the course of the human papillomavirus (HPV) infection and cytokines play an important role modulating viral multiplication and concentrating the immune response in the Th1 or Th2 pattern. The aim of this study is to evaluate the available evidence on the concentration of genital cytokines and their role in HPV infection in HIV-infected women. A systematic search of the literature was performed using MEDLINE by PubMed, Embase, Cochrane, LILACS, Scopus, Science direct, and Web of Science databases on November, 2020, in which the following clusters of terms were applied: HIV infection, HPV infection, and cytokine. Initially, 728 articles were selected, but only 17 were eligible for full-text review, and among them, 9 were included in the qualitative analysis. No restriction was applied in language, publication date, or status. The most studied cytokines in the articles included in this review were interferon (IFN)-γ and interleukin (IL)-10 (six articles), tumor necrosis factor (TNF) and IL-6 (five articles), and macrophage inflammatory protein (four articles). The main findings show that there is a reduction in the number of cells expressing IFN-γ (p = .02) and TNF-α (p = .01), in the cervices of HIV-HPV co-infected women compared with those infected only by HPV. In addition, levels of IL-6 (p = .039) and IL-10 (p = .02) are increased in the cervical secretions of HIV-positive women compared to seronegative patients. Despite these findings, there is a clear need of larger studies to understand the role of these immune factors in HPV-induced cervical neoplasia of women co-infected with HIV.

HPV and premature delivery risk

Preterm delivery represents the leading cause of perinatal morbidity and mortality. Among possible etiologies of premature birth are the infectious ones, Human Papilloma Virus (HPV) infection being less documented than others. The available data on the role of HPV infection in premature delivery pathogenesis is limited and controversial. This review article attempts to make an assessment of current information on the risk of premature delivery in women with HPV infection during pregnancy. A systematic literature electronic search for journal articles and guidelines regarding HPV infection during pregnancy was undertaken. The relationship between HPV infection and pregnancy is bidirectional, as physiological changes that occur during pregnancy modulate the mechanisms of HPV infection and HPV infection determine adverse maternal, obstetrical, and fetal outcomes.

The Potential Role of Human Papillomavirus Infection in Bell's Palsy: A Hypothesis-Generating Study Based on a Nationwide Cohort.

Objective: Our purpose was to investigate whether people with a previous human papillomavirus (HPV) infection were associated with an increased risk of Bell's palsy (BP).Methods: By using Taiwan population-based data, patients aged > 18 years with HPV infection (n = 22,260) from 2000 to 2012 were enrolled and compared with control subjects who had never been diagnosed with an HPV infection at a 1:4 ratio matched by sex, age, index date, and co-morbidities (n = 89,040). The index date was the first date of HPV diagnosis. All the patients were tracked until the occurrence of BP. Cox proportional hazards regression was applied to estimate the hazard ratios (HRs) for the development of BP in both groups.Results: The HPV group had 1.25 [95% confidence interval (CI) = 1.03–1.51] times higher risk of BP compared with the non-HPV group after adjusting for sex, age, and co-morbidities. The association of HPV and BP was significant in the sensitivity analyses. In the subgroup analysis, the impact of HPV infection on the risk of BP was more pronounced in the elderly > 50 years [adjusted hazard ratio (aHR) =1.86; 95% CI = 1.37–2.52], hypertension (aHR = 1.65; 95% CI = 1.17–2.31), and chronic obstructive pulmonary disease (aHR = 2.14, 95% CI 1.333.43) subgroups.Conclusions: Patients with HPV infection have a higher risk of subsequent BP compared with non-HPV patients. More rigorous studies are needed to confirm if and how specific HPV genotypes are associated with BP and the possible role of vaccines in disease prevention.

HPV Infection in Middle Ear Squamous Cell Carcinoma: Prevalence, Genotyping and Prognostic Impact.

Middle ear squamous cell carcinoma (MESCC) is rare. Human Papilloma Virus (HPV) infection has been found in a significant number of cases of MESCC. Despite the emerging role of HPV in oncogenesis, its role in the pathogenesis and prognosis of MESCC is not known. This study aims to identify the prognostic impact of alpha and beta HPV in MESCC and its correlation with p16 protein. We retrospectively investigated 33 patients with MESCC surgically treated between 2004 and 2016. HPV DNA was ascertained by polymerase chain reaction (PCR) and P16INK4a detection was performed. Disease-specific survival (DSS) and cumulative incidence of recurrence were calculated in relation to HPV presence and genotype. p16 sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in predicting HPV infection were calculated. HPV was detected in 66.7% of patients (36.4% alpha HPV, 63.6% beta HPV). Five-year DSS was 55.0% and was not statistically related to HPV presence (p = 0.55) or genotype (p = 0.87). Five-year cumulative incidence of recurrence was 46 %, and was not statistically related to HPV presence (p = 0.22) or genotype (p = 0.44). p16 sensitivity, specificity, PPV, and NPV in predicting HPV infection were 27.3%, 36.4%, 46.2%, and 20.0%, respectively. In our experience, beta HPV was more frequent than alpha HPV in MESCC. Neither HPV presence nor HPV genotypes relate to DSS or cumulative incidence of recurrence. p16 expression was not predictive for HPV infection in MESCC. The role of HPV infection in oncogenesis, maintenance, and prognosis of MESCC seems to be different from that in oropharynx and skin cancer.

Role of Human Papillomavirus Infection in Head and Neck Cancer in Italy: The HPV-AHEAD Study.

Simple SummaryThis is the largest and most comprehensive assessment of the role of human papillomavirus (HPV) in head and neck cancer (HNC) in Italy, which is a region currently considered bearing a low burden of HPV-driven HNC. p16INK4a, HPV-DNA, and HPV RNA biomarkers were used to assess the HPV status in head and neck cancer in a retrospective cohort of approximately 700 patients. In our study, HPV prevalence in oropharyngeal cancers was much higher than in oral and laryngeal cancers, and HPV positivity conferred better prognosis only in oropharyngeal cancers. Importantly, we have observed an increase of the prevalence of HPV positivity in oropharyngeal cancers in the most recent calendar periods, suggesting that this disease is increasing in Italy, as has happened before in other developed regions.Literature on the role of human papillomavirus (HPV) in head and neck cancer (HNC) in Italy is limited, especially for non-oropharyngeal tumours. Within the context of the HPV-AHEAD study, we aimed to assess the prognostic value of different tests or test algorithms judging HPV carcinogenicity in HNC and factors related to HPV positivity at the European Institute of Oncology. We conducted a retrospective cohort study (2000–2010) on a total of 696 primary HNC patients. Formalin-fixed, paraffin-embedded cancer tissues were studied. All HPV-DNA-positive and a random sample of HPV-DNA-negative cases were subjected to HPV-E6*I mRNA detection and p16INK4a staining. Multivariate models were used to assess for factors associated with HPV positivity and proportional hazards for survival and recurrence. The percentage of HPV-driven cases (considering HPV-E6*I mRNA positivity) was 1.8, 2.2, and 40.4% for oral cavity (OC), laryngeal (LC), and oropharyngeal (OPC) cases, respectively. The estimates were similar for HPV-DNA/p16INK4a double positivity. Being a non-smoker or former smoker or diagnosed at more recent calendar periods were associated with HPV-E6*I mRNA positivity only in OPC. Being younger was associated with HPV-E6*I mRNA positivity in LC. HPV-driven OPC, but not HPV-driven OC and LC, showed better 5 year overall and disease-free survival. Our data show that HPV prevalence in OPC was much higher than in OC and LC and observed to increase in most recent years. Moreover, HPV positivity conferred better prognosis only in OPC. Novel insights on the role of HPV in HNC in Italy are provided, with possible implications in the clinical management of these patients.

Human Papillomavirus 16 L2 Recruits both Retromer and Retriever Complexes during Retrograde Trafficking of the Viral Genome to the Cell Nucleus.

Previous studies have identified an interaction between the human papillomavirus (HPV) L2 minor capsid protein and sorting nexins 17 and 27 (SNX17 and SNX27) during virus infection. Further studies show the involvement of both retromer and retriever complexes in this process since knockdown of proteins from either complex impairs infection. In this study, we show that HPV L2 and 5-ethynyl-2'-deoxyuridine (EdU)-labeled pseudovirions colocalize with both retromer and retriever, with components of each complex being bound by L2 during infection. We also show that both sorting nexins may interact with either of the recycling complexes but that the interaction between SNX17 and HPV16 L2 is not responsible for retriever recruitment during infection, instead being required for retromer recruitment. Furthermore, we show that retriever recruitment most likely involves a direct interaction between L2 and the C16orf62 subunit of the retriever, in a manner similar to that of its interaction with the VPS35 subunit of retromer.IMPORTANCE Previous studies identified sorting nexins 17 and 27, as well as the retromer complex, as playing a role in HPV infection. This study shows that the newly identified retriever complex also plays an important role and begins to shed light on how both sorting nexins contribute to retromer and retriever recruitment during the infection process.

Effects of human papillomavirus infection on prevalence of colorectal cancer: a systematic review and meta-analysis of global data

BackgroundSeveral studies have emerged in the past two decades investigating the role of human papillomavirus infection in colorectal cancer development. To better inform global prevention strategies for colorectal cancer, we reviewed available evidence on the associations between human papillomavirus infection and colorectal cancer. MethodsIn this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane Library, Web of Science, and websites of international conferences for studies published before Dec 31, 2019. Interventional or observational studies containing original quantitative data describing associations between human papillomavirus and incidence or prevalence of colorectal cancer were included. We calculated pooled odds ratios (ORs) and their 95% CIs using random-effect models. We assessed risk of bias using the Newcastle-Ottawa scale. FindingsWe identified 20 observational studies including 1424 cases of colorectal cancer or adenoma and 1363 controls. The prevalence of human papillomavirus was 34·5% in the group with colorectal cancer or adenoma and 17% in the control group. Human papillomavirus was associated with a three-fold increase in colorectal cancer overall (OR 3·05, 95% CI 2·01–4·62; heterogeneity I2 63·5%). In the subgroup analysis, human papillomavirus was associated with increased colorectal cancer prevalence in controls (2·96, 1·16–7·61; I2 75·3%) and in the group with adjacent normal tissues (3·05, 2·12–4·40; I2 31·2%). InterpretationWe found evidence that human papillomavirus is likely to be associated with increased colorectal cancer prevalence. Prevention of human papillomavirus infection could be considered for inclusion in campaigns promoting prevention strategies for colorectal cancer. FundingThe National Key R&D Programme of China (2018YFC1315000/2018YFC1315003).