Impact Of Human Papillomavirus Infection Research Articles

Changes in microbial composition and interaction patterns of female urogenital tract and rectum in response to HPV infection

BackgroundPrevious studies have shown that changes in the microbial community of the female urogenital tract are associated with Human papillomavirus (HPV) infection. However, research on this association was mostly focused on a single site, and there are currently few joint studies on HPV infection and multiple sites in the female urogenital tract.MethodsWe selected 102 healthy women from Yunnan Province as the research object, collected cervical exfoliation fluid, vaginal, urethral, and rectal swabs for microbial community analysis, and measured bacterial load, and related cytokine content. The link between HPV, microbiota, and inflammation was comprehensively evaluated using bioinformatics methods.FindingsThe impact of HPV infection on the microbial composition of different parts varies. We have identified several signature bacterial genera that respond to HPV infection in several detection sites, such as Corynebacterium, Lactobacillus, Campylobacter, and Cutibacterium have been detected in multiple sites, reflecting their potential significance in cross body sites HPV infection responses. There was a solid microbial interaction network between the cervix, vagina, and urethra. The interrelationships between inflammatory factors and different bacterial genera might also affect the immune system's response to HPV infection.InterpretationIt might be an effective strategy to prevent and treat HPV infection by simultaneously understanding the correlation between the microbial changes in multiple parts of the female urogenital tract and rectum and HPV infection, and controlling the microbial network related to HPV infection in different parts.

P-038 Correlation between sperm DNA fragmentation index, semen parameters and Human Papillomavirus: an analysis conducted under World Health Organization 2021 guidelines

Abstract Study question Following 6thWHO (2021), we analysed the correlation between DNA fragmentation index (DFI), Human papillomavirus (HPV), and seminal parameters, highlighting slow and rapid progressive motility alterations. Summary answer DFI rates and seminal parameters correlated with rapid, slow, and progressive motility. However, HPV-positivity caused the loss of association between DFI and slow progressive motility. What is known already HPV detection in semen samples has long opened an investigation into its influence on male infertility. Some studies indicate that HPV can affect sperm quality and DFI, while others have failed to find any correlation. With reference to 2010 WHO guidelines, our latest work highlighted how HPV positivity significantly impairs progressive motility, morphology, and immotile sperm rate. Since the latest 2021 WHO guidelines included the evaluation of slow and rapid progressive motility and DFI, we analysed if these new parameters and the other conventional parameters could be altered by HPV infection. Study design, size, duration From August 2021 to December 2022, 121 semen samples were collected from male partners of HPV-positive women attending in vitro fertilization (IVF). Every specimen underwent DFI evaluation, analysis of seminal parameters, and HPV test. Participants/materials, setting, methods Seminal samples were collected by masturbation after 3-5 days of sexual abstinence. The inclusion criteria were as follows: no other sexually transmitted infections, no genetic diseases, and no inflammatory disorders. Sperm concentration, morphology, non-progressive and immotile sperms, and both slow and rapid progressive motility were evaluated according to WHO 2021 guidelines. DFI analysis was assessed by sperm chromatin dispersion test (SCD), while HPV-DNA detection was performed using InnoLipa HPV Genotyping Extra II (Fujirebio, Tokyo, Japan). Main results and the role of chance Of the 121 semen samples tested, 60 (49.6%) were HPV-positive and 61 (50.4%) were HPV-negative. DFI rates showed a significant negative correlation with rapid progressive motility in both groups and a positive correlation with slow progressive motility in the HPV-negative group. Conversely, the significance of the correlation between DFI and slow progressive motility was completely lost in HPV-positive patients. Sperm concentration, normal forms and immotile spermatozoa percentages were correlated with both motility parameters in the HPV-negative group. Similar results were observed in HPV-positive samples, except for the normal form rate, which was not associated with slow progressive motility. In addition, the same samples displayed a negative correlation between non-progressive motility and rapid progressive motility, absent in HPV-negative samples. Significant associations were found also for the derived parameter of progressive motility, which was correlated with DFI, sperm concentration, immotile sperm, and normal forms rate in both groups. The results suggest how high DFI rates, in the presence or absence of HPV infection, could affect reproductive health through a consistent impairment of spermatozoa motility. In particular, the distinction of slow and rapid progressive motility by WHO 2021 allows a deeper understanding of the possible correlations between DFI, semen parameters and HPV infection. Limitations, reasons for caution This is a preliminary study characterized by a small number of samples. Therefore, confirmation of these findings requires the enlargement of the patient cohort, which is already taking place. Wider implications of the findings Our results highlight how the introduction of the new WHO 2021 evaluation criteria, i.e. DFI, and slow and rapid progressive motility, provides additional information about sperm quality and the impact of HPV infection on it. Trial registration number Not applicable

Факторы формирования неопластических процессов в шейке матки

Aim: Review the literature data on the pathogenetic aspects of the formation of squamous intraepithelial lesions and the role of immunological mechanisms in the formation of this group of cervical diseases. Key Points. Cervical cancer (CC) is a multi-stage process that is often preceded by human papillomavirus (HPV)-associated intraepithelial lesions. The establishment of causal interactions between the virus and malignancy, as well as the study of epidemiological data, leads to the formation of models of cervical carcinogenesis: infection, persistence, progression to the precancerous stage, and finally, cervical cancer. Despite the clear and obvious path of malignancy, as well as the availability of generally available diagnostic methods in the arsenal of a practicing obstetrician-gynecologist, the assessment and prediction of the further development of cervical pathologies in patients of active reproductive age remains difficult. In general, cervical cancer can be considered an excellent model for understanding the staging of malignancy processes, which will be primarily associated with the impact of human papillomavirus infection and changes in the immunological aspects of endo-and exo-cervix. Conclusion. An analysis of sources published in the Cochrane Librare, Google Scolare and PubMed systems was carried out. In recent years, the understanding of human papillomavirus-associated tumor interaction with the host immune system has improved, so the development of new approaches targeting immune checkpoints has sparked interest in the use of immunotherapy in cervical cancer. CC is curable if detected at an early stage. However, reliable diagnostic and prognostic markers related to the physiological and pathological regulation of cervical cancer are currently not available. Therefore, the approach to the treatment of cervical cancer has remained unchanged for several decades, and new diagnostic strategies are currently required, due to the interaction of the immune system and the virus. Keywords: genotyping, apoptosis, cervical neoplasia, polymerase reaction, interleukin-18, tumor necrosis factor alpha, viral load.

Human Papillomavirus (HPV) Infection and Its Impact on Male Infertility.

Nowadays, the striking numbers of infertile couples that turn to assisted reproductive technologies (ART) drive the research toward a more comprehensive understanding of the underlying causes. Male factors contribute to the inability to conceive in half of the cases, and it has been suggested that sexually transmitted infections could have a role in the onset of spermatozoa impairments. Since the impact of HPV infection on sperm quality and sperm DNA integrity is debated, we wanted to analyze its impact on conventional seminal parameters and the sperm DNA fragmentation index (DFI). Therefore, 117 semen samples of patients undergoing IVF were evaluated for the following characteristics: HPV DNA detection and sperm DNA fragmentation, concentration, motility, and morphology. The results showed a higher rate of HPV-negative patients (59.8% vs. 40.2%) and no HPV-related effect on DFI, sperm concentration, total sperm number, and total motility. Only progressive motility and morphology were found as significantly influenced by HPV positivity. Moreover, we observed a statistically significant difference in DFI when comparing high-risk HPV (HR-HPV) and low-risk HPV (LR-HPV) genotypes. Our data suggest that the presence of any HPV type, whatever the exact localization of the virions, can impair some sperm parameters, while HR-HPVs specifically affect the integrity of spermatozoa DNA.

LITERATUR REVIEW: HAMBATAN PROGRAM PENCEGAHAN HUMAN PAPILLOMAVIRUS (HPV) DAN ANCAMAN INFEKSI HPV PADA PASANGAN

Human papillomavirus (HPV) is the cause of cervical cancer.
 However, the HPV prevention program has not been maximized. The impact of HPV infection is not only on women but also on men. The purpose of the literature review is to review HPV prevention programs and the impact of poor implementation of prevention. Literature review is carried out based on the suitability of the theme of the review and the article. Systematic literature search using database from PubMed. Then the prevention and impact of the HPV prevention program was analyzed using the keywords “Human papilovavirus”, “infection”, “impact” and “prevention” in combination with various other keywords. Of the 6 articles that met the inclusion criteria found, it was found that HPV prevention was carried out using vaccination and screening in women and men. However, there are obstacles in its implementation that can cause health impacts on women, men and fetuses.

The Association Between Human Papillomavirus Infection and Preterm Labor: A Literature Mini-review

: Human papillomavirus (HPV) is the primary cause of cervical dysplasia and the most common sexually-transmitted infection. Based on the available studies, HPV infection appears to correlate with adverse pregnancy outcomes, including preterm labor. However, there is inconsistency in the literature regarding this association. In this context, the aim of this mini-review was to bring together current research findings focusing on the impact of HPV infection on preterm birth.

Modelling the Impact of Spread of Human Papillomavirus Infections under Vaccination in Kenya

Human Papillomavirus (HPV), a sexually transmitted virus is a collection of more than 40 types of viruses, some of which are linked to several cancers. HPV type 16 and HPV type 18 are accountable for 70% of cervical cancer cause. Besides cervical cancer, HPV has been linked to several cancers such as anal cancer, oropharyngeal cancer and neck cancer. Mathematical models have been used in the evaluation of control strategies and making of health policies. Very few mathematical models have been developed on HPV awareness in Kenya. In this study we developed a deterministic model on the impact of HPV infection under vaccination. In this model we incorporated an ineffective media awareness. We computed the equilibrium points of the model and local and global stability analysis was conducted on the reproduction number. The numerical simulation results show that the HPV infections continue to stay in the community due to the ineffective mass media awareness. Sensitivity analysis show that the infection contact rate and negative attitudes influencing condom use rate are parameters that contribute to the persistence of HPV infections in the community.

Prognostic impact of human papillomavirus infection on cervical dysplasia, cancer, and patient survival in Saudi Arabia: A 10-year retrospective analysis.

BACKGROUND: Data on human papillomavirus (HPV) prevalence and survival rates among HPV-infected women are scarce in Saudi Arabia.OBJECTIVE: Assess the prevalence of HPV genotypes in cervical biopsy specimens and its effect on survival over a 10-year timeframe.DESIGN: Retrospective, cross-sectional.SETTINGS: Saudi referral hospital.PATIENTS AND METHODS: Cervical biopsy specimens were collected from women aged 23-95 years old who underwent HPV detection, HPV genotyping, p16INK4a expression measurement using immunohistochemistry. Kaplan-Meier plots were constructed to analyze overall survival rates.MAIN OUTCOME MEASURES: Survival rate of HPV-positive cervical cancer patients.SAMPLE SIZE: 315 cervical biopsy specimens.RESULTS: HPV was detected in 96 patients (30.4%): 37.3% had cervical cancer; 14.2% cervical intraepithelial neoplasia (CIN) III, 4.1% CIN II, and 17.0% CIN I. A significant association was found between HPV presence and cervical cancer (χ2=56.78; P<.001). The expression of p16INK4a was a significant predictor of survival: women who had p16INK4a overexpression had poorer survival rates (multivariate Cox regression, hazard ratio, 3.2; 95% CI, 1.1–8.8). In addition, multivariate models with HPV status and cervical cancer diagnosis showed that HPV status was a significant predictor of survival: HPV-positive women had better survival rates than HPV-negative women.CONCLUSION: These findings suggest that implementing cervical and HPV screening programs may decrease cervical cancer rates and improve survival rates of women in Saudi Arabia.LIMITATION: Single center and small sample size.CONFLICT OF INTEREST: None.

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.

Abstract 770: High-grade neuroendocrine carcinoma of the oropharynx: A rare entity with prognosis unaffected by HPV

Abstract Background: Human Papilloma Virus (HPV) infection is associated with a better prognosis in oropharynx squamous cell carcinomas. Neuroendocrine carcinoma (NEC) of the oropharynx is a rare variant that can be associated with HPV infection, however little is known regarding clinical behavior and the impact of HPV infection on its prognosis. This study aims to evaluate clinical and pathologic features of oropharyngeal high-grade NEC and to investigate the prognostic value of HPV and smoking in this rare histological subtype. Methods: Patients with high-grade NEC from oropharynx were identified through electronic medical records queries from 1997 to 2020. A cohort of 27 patients with sufficient pathological and clinical data were included in the analysis. Neuroendocrine differentiation was confirmed by immunoreactivity for synaptophysin, chromogranin and/or CD56. P16 immunohistochemistry staining or HPV in situ hybridization or polymerase chain reaction were performed in all patients' samples. Disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method. The log-rank test was used to assess difference in survival between groups. Results: Of 27 patients, 25 were male and 10 had a heavy smoking history (≥10-pack-years). P16 staining was positive in 24 (89%) samples and HPV was confirmed in 15 (62.5%). Most patients (22/27; 81.5%) presented with locoregional disease, 8 (35%) received induction chemotherapy, and 18 of 23 (78%) achieved a complete response after definitive therapy (surgery and/or radiation); among them, 7 (30%) recurred. Most recurrences were distant and common sites of metastasis was liver (56%), bone (56%) and lymph nodes (50%). In the palliative setting, 85% of patients received platinum-based chemotherapy and preferred combined agents were etoposide (6/14) and docetaxel (5/14). The overall response rate to first- and second-line systemic therapy were 50% and 0%, respectively. The median DFS for those patients who achieved a complete response to definitive therapy was 61.0 months (95% CI 13.0-NA) and 1- and 2-year DFS rates were 73.3% and 56.4%, respectively. The median OS was 28.8 months (95%CI 14.3-NA) for the overall population. Metastasis at diagnosis was associated with lower median survival (9.5 versus 62.0 months, p= 0.016). We have not found differences in median OS according to HPV status(positive 28.9 versus negative 28.8 months, p= 0.93) or smoking exposure (≥10pack/year 47.2 versus &amp;lt;10pack/year 14.3 months, p= 0.8). Conclusions: Distinct from oropharynx squamous cell carcinoma, HPV status is not an independent prognostic factor for high-grade NEC of the oropharynx. Although high-grade NEC is usually associated with a dismal prognosis, most patients with loco-regional disease were cured, suggesting primary disease site has biologic implications. This represents the largest case series of oropharyngeal high-grade NEC. Citation Format: Luana Sousa, Felippe Lazar, Danice Torman, Kaiyi Li, Andrew Sikora, Amy Moreno, Ehab Hanna, Jack Phan, Bonnie Glisson, Diana Bell, Renata Ferrarotto. High-grade neuroendocrine carcinoma of the oropharynx: A rare entity with prognosis unaffected by HPV [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 770.

Impact of HPV infection on vaginal microecology and maternal and neonatal outcomes.

Human papillomavirus (HPV) is a kind of spherical DNA virus, which is related to many factors such as immune status and pregnancy. Due to the decrease of immunity, pregnant women are more likely to have HPV infection, which causes serious imbalance of vaginal microecology and is not beneficial to pregnancy outcome. Therefore, this study focuses on the impact of HPV infection on vaginal microecology and maternal and neonatal outcomes. A total of 140 pregnant women with HPV infection during pregnancy, who received obstetric examination in the First Affiliated Hospital of Hainan Medical College from November 2017 to July 2019, were selected as a HPV infection group, and 150 normal pregnant women with HPV negative in the same period were selected as a control group. Vaginal secretions were collected from all the pregnant women at 28-34 weeks of gestation to evaluate vaginal pH, cleanliness and microecological status, and to record pregnancy outcomes for all pregnant women. The proportions of vaginal pH>4.5, constituent ratio of flora density and diversity of I-II, positive detection rate of vulvovaginal candidiasis (VVC) and bacterial vaginosis (BV) in HPV infected pregnant women were significantly higher than those in the control group (all P<0.05). There was no significant difference in vaginal cleanliness, dominant bacteria classification, detection rate of trichomonas vaginitis (TV), BV negative, and BV intermediate type between the 2 groups (all P>0.05). The incidence of microecological imbalance in pregnant women with HPV infection was significantly higher than that in the control group (P<0.05). There was no significant difference in natural delivery rate and cesarean section rate between the control group and the HPV infection group (P>0.05). The incidences of premature delivery, puerperal infection, postpartum hemorrhage, and chorioamnionitis in the HPV infection group were significantly higher than those in the control group (all P<0.05). There was no significant difference in the incidence of premature rupture of membranes between the 2 groups (P>0.05). The incidences of premature delivery, postpartum hemorrhage, and premature rupture of membranes of HPV-infected pregnant women in microecological imbalance group were significantly higher than those in the microecological normal group (all P<0.05). There was no significant difference in the incidences of puerperal infection and chorioamnionitis between the microecological normal group and the microecological imbalance group (all P>0.05). Pregnant women with HPV infection during pregnancy are more likely to have vaginal microecological disorders, and can increase the risk of adverse pregnancy outcomes such as premature delivery and chorioamnionitis.

MiRNA Expression Characterizes Histological Subtypes and Metastasis in Penile Squamous Cell Carcinoma.

Simple SummaryPenile squamous cell carcinoma (PSCC) is the most common type of penile cancer (PeCa) and is associated with human papillomavirus (HPV) in about 50% of cases. It is of high clinical impact to identify patients who are at high risk of metastasis and are likely to benefit from adjuvant therapies. Today, valid prognostic biomarkers are scarce in penile cancer. In the present study, we attempted to identify miRNAs involved in tumor development and metastasis in distinct histological subtypes with or without HPV infection in PSCC patients. We confirmed that specific miRNAs could serve as potential diagnostic and prognostic markers in single PSCC subtypes and are associated with HPV infection.Although microRNAs are described as promising biomarkers in many tumor types, little is known about their role in PSCC. Thus, we attempted to identify miRNAs involved in tumor development and metastasis in distinct histological subtypes considering the impact of HPV infection. In a first step, microarray analyses were performed on RNA from formalin-fixed, paraffin-embedded tumor (22), and normal (8) tissue samples. Microarray data were validated for selected miRNAs by qRT-PCR on an enlarged cohort, including 27 tumor and 18 normal tissues. We found 876 significantly differentially expressed miRNAs (p ≤ 0.01) between HPV-positive and HPV-negative tumor samples by microarray analysis. Although no significant differences were detected between normal and tumor tissue in the whole cohort, specific expression patterns occurred in distinct histological subtypes, such as HPV-negative usual PSCC (95 differentially expressed miRNAs, p ≤ 0.05) and HPV-positive basaloid/warty subtypes (247 differentially expressed miRNAs, p ≤ 0.05). Selected miRNAs were confirmed by qRT-PCR. Furthermore, microarray data revealed 118 miRNAs (p ≤ 0.01) that were significantly differentially expressed in metastatic versus non-metastatic usual PSCC. The lower expression levels for miR-137 and miR-328-3p in metastatic usual PSCC were validated by qRT-PCR. The results of this study confirmed that specific miRNAs could serve as potential diagnostic and prognostic markers in single PSCC subtypes and are associated with HPV-dependent pathways.

The Impact of Human Papillomavirus Infection on Skin Cancer: A Population-Based Cohort Study.

This study investigated the correlation between a history of human papillomavirus (HPV) infection and skin cancer risk. The study cohort comprised 26,919 patients with newly diagnosed HPV infection between 2000 and 2012; with the use of computer-generated numbers, patients without previous HPV infection were randomly selected as the comparison cohort. The patients in the HPV infection cohort were matched to comparison individuals at a 1:4 ratio by demographic characteristics and comorbidities. All study individuals were followed up until they developed skin cancer, withdrew from the National Health Insurance program, were lost to follow-up, or until the end of 2013. The primary outcome was subsequent skin cancer development. Cox proportional hazards regression analysis was used to analyze the risk of skin cancer with hazard ratios (HRs) and 95% confidence intervals (CIs) between the HPV and control cohort. The adjusted HR of skin cancer for patients with HPV relative to controls was 2.45 after adjusting sex, age and comorbidities. (95% CI, 1.44-4.18, p < .01). The subgroup analysis indicated that a patient with HPV infection had a significantly greater risk of skin cancer if they were aged >40 years. Notably, a risk of skin cancer was found in the group diagnosed with HPV within the first 5 years after the index date (adjusted HR, 3.12; with 95% CI, 1.58-5.54). Sensitivity analysis by propensity score, matching with balanced sex, age, and comorbidities, showed consistent results. A history of HPV infection is associated with the development of subsequent skin cancer in Taiwanese subjects, and the risk wanes 5 years later. In this Taiwan nationwide cohort study, there was a 2.45-fold increased risk of developing new-onset skin cancers for patients with incident human papillomavirus (HPV) infection, compared with the matched controls. Furthermore, the risk was noticeably significant among patients aged >40 years. A prominent risk of skin cancers was found in the group diagnosed with HPV within the first 5 years after the index date in this study. The results of this analysis may raise consensus on the effect of HPV infection on the risk of skin cancers. Clinicians are encouraged to implement prudently on the differential diagnosis of skin cancers and HPV prevention and treatment, especially in older patients.

Prognosis prediction signature of seven immune genes based on HPV status in cervical cancer

Cervical cancer (CC) has a high incidence and mortality rate, with a low 5-year survival rate, and human papillomavirus (HPV) is one of its carcinogenic risks. However, little evidence exists on the impact of HPV infection on the survival of patients with CC. In the present study, the CC cohort and immune genes were downloaded from the TCGA database and the ImmPort database, respectively. Subsequently, the Gene Set Enrichment Analysis was performed and found that HPV status was involved in multiple immune signaling pathways, which revealed that HPV infection might play critical roles in the immune response. Then seven prognostic immune genes were identified according to HPV status in CC. Using the seven immune genes, we established an immune risk score (IRS) signature and the Kaplan-Meier curve showed that high IRS was significantly correlated with poor prognosis of CC in both the training sets (HR = 2.32, 95% CI = 1.66–3.33; AUC = 0.712) and the validation sets (HR = 1.38, 95% CI = 1.02–1.85 and AUC = 0.583 in TCGA-HNSCC; HR = 2.58, 95% CI = 1.364–4.893, AUC = 0.676 in GSE44001). A nomogram of IRS combined with clinical features was established, and further analyses demonstrated that the power of the nomogram to predict the prognosis of CC was more reliable than that of a single independent factor. In conclusion, this study provided a more comprehensive understanding of the correlation between HPV and immune mechanisms as well as a novel signature that can effectively predict the prognosis of CC patients.

HPV Involvement in the Tumor Microenvironment and Immune Treatment in Head and Neck Squamous Cell Carcinomas.

Head and neck squamous cell carcinomas (HNSCC) are one of the most prevalent cancers worldwide. Active human papillomavirus (HPV) infection has been identified as an important additional risk factor and seems to be associated with a better prognosis in non-drinker and non-smoker young patients with oropharyngeal SCC. The better response of the immune system against the HPV-induced HNSCC is suspected as a potential explanation for the better prognosis of young patients. To further assess this hypothesis, our review aims to shed light the current knowledge about the impact of HPV infection on the immune response in the context of HNSCC, focusing on the innate immune system, particularly highlighting the role of macrophages, Langerhans and myeloid cells, and on the adaptative immune system, pointing out the involvement of T regulatory, T CD8 and T CD4 lymphocytes. In addition, we also review the preventive (HPV vaccines) and therapeutic (checkpoint inhibitors) strategies against HPV-related HNSCC, stressing the use of anti-CTLA4, PD-L1, PD-L2 antibodies alone and in combination with other agents able to modulate immune responses.

Impact of human papillomavirus status on survival and recurrence in a geographic region with a low prevalence of HPV-related cancer: A retrospective cohort study.

Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is associated with better tumor-response rates and survival outcomes. However, in some geographic regions, the impact of HPV infection on prognosis remains unclear. The aim of this study was to describe the patterns of recurrence and survival among patients treated for OPSCC in a geographic region with a reported low prevalence of HPV-related OPSCC. We retrospectively evaluated 215 patients diagnosed with American Joint Committee on Cancer (AJCC) stages I to IV OPSCC who were treated with upfront surgery or radiation therapy with or without chemotherapy in a tertiary Cancer Center in Brazil. The collected data included demographic information, HPV status, tobacco and alcohol consumption, and pathologic and treatment variables. The patterns of recurrence were recorded according to HPV status. Disease-specific survival and recurrence-free survival were calculated. One hundred twenty-seven (59.1%) patients were diagnosed with HPV-positive OPSCC. According to the AJCC eighth edition, 34 (15.8%), 71 (33%), 47 (21.9%), and 60 (27.9%) patients had stage I, II, III, and IV disease, respectively. Surgery was performed in 109 (50.7%) cases, and upfront chemoradiation regimens were provided in 104 (48.4%, P = .69) patients. Overall, the 5-year cancer-specific survival was 73.5% and 68.1% for patients positive and negative to HPV, respectively. Tobacco status was considered the only independent prognostic factor for survival. Furthermore, HPV status was not associated with differences in recurrence rates (P = .68). While all distant relapses were found to be lung metastases in the HPV-negative group, we observed unusual sites of distant metastases in the HPV-positive group. HPV status was not associated with higher rates of survival among the investigated population. Moreover, smoking status was considered the only independent prognostic factor for survival. Furthermore, patients with HPV-positive tumors were more likely than patients with HPV-negative OPSCC to have unusual distant metastases.

Prognostic relevance of human papillomavirus infection in anal squamous cell carcinoma: Analysis of the National Cancer Database.

735 Background: To examine the prognostic relevance of human papillomavirus (HPV) infection for anal squamous cell carcinoma (ASCC) patients treated with chemoradiation in the National Cancer Database (NCDB). Methods: The 2014 NCDB was queried for non-metastatic, histologically confirmed, ASCC patients diagnosed between 2004 and 2013. Patients were required to have HPV status documented in order to be eligible. Patients were then stratified into two groups: HPV+ and HPV-. Univariate analysis was performed using the χ2 test for categorical covariates and ANOVA for numerical covariates. Multivariable analysis (MVA) was performed using Cox proportional hazard model for overall survival (OS). Hazard ratios (HR) and 95% confidence intervals (CI) were generated for each covariate. To minimize selection bias, propensity score (PS) weighting was implemented to balance OS related variables between the groups including: age, education level, stage, diagnosis year, insurance type, and agent of chemotherapy. Results: A total of 1,063 patients were eligible. Patients were stratified into HPV+ (n = 498, 46.8%) and HPV- (n = 565, 53.2%). After PS weighting, MVA for OS showed that for men, HPV infection was associated with better OS (HR 0.60, CI 0.38-0.96; p = 0.034). However, for women, HPV infection did not significantly influence survival (HR 1.47, CI 0.96-2.25; p = 0.074). Conclusions: To our knowledge, this is the largest patient series evaluating the impact of HPV infection on OS in patients with anal cancer. We found that HPV infection is associated with a statistically significant better survival for men with ASCC. In contrast, for women, HPV infection did not significantly influence survival.

High infiltration of CD68+ macrophages is associated with poor prognoses of head and neck squamous cell carcinoma patients and is influenced by human papillomavirus.

Incidence of human papillomavirus (HPV)-related head and neck squamous cell carcinomas (HNSCCs) has increased over the last few decades. The reaction of the host immune system to these tumors remains biologically complex. Here, we investigated CD68+ macrophage numbers, reporting the prognostic value in comparison to other risk factors. We also examined CD68+ macrophage infiltration during disease progression regarding the impact of HPV infection, and we studied the role of HPV16-E6/E7 oncoproteins in CD68+ macrophage recruitment. CD68+ macrophage numbers were evaluated in 10 cases of tumor-free peri-tumoral epithelia, 43 cases of low-grade dysplasia, 45 cases of high-grade dysplasia and 110 cases of carcinoma. Our in vivo model was developed in 80 C3H/HeN mice orthotopically injected with HPV16-E6, -E7 or -E6/E7-transfected SCC-VII cell lines. High CD68+ macrophage numbers in the intra-tumoral compartment were associated with shorter patient survival (recurrence-free survival: p = 0.001; overall survival: p = 0.01). Multivariate analyses reported that CD68+ macrophage infiltration and tumor stage were strong and independent prognostic factors of HNSCC. CD68+ macrophage numbers increased during HNSCC progression both in intra-epithelial (p < 0.001) and stromal compartments (p < 0.001). A higher density of CD68+ macrophages was observed in advanced stages (p = 0.004). Patients with transcriptionally active HPV infections had higher CD68+ macrophage density than did HPV-negative patients (p = 0.003). CD68+ macrophage infiltration was higher in HPV-E7+ and −E6/E7+ mouse tumors than in -E6+ tumors (p = 0.029 and p < 0.001). In conclusion, the extent of CD68+ macrophage infiltration is a significant prognostic factor for HNSCC patients. The recruitment of macrophages increases during disease progression and is influenced by the HPV virus.

Impact of Human Papillomavirus Infection on Radiosensitivity of Head and Neck Cancers

Impact of Human Papillomavirus Infection on Radiosensitivity of Head and Neck Cancers

Alterations in the expression and activity of extracellular matrix components in HPV-associated infections and diseases

Infection with human papillomaviruses is associated with a series of benign and malignant hyperproliferative diseases that impose a heavy burden on human populations. A subgroup of mucosal human papillomavirus types are associated with the majority of cervical cancers and a relevant fraction of vulvar, vaginal, anal, penile and head and neck carcinomas. Human papillomaviruses mediate cell transformation by the expression of two pleiotropic oncoproteins that alter major cellular regulatory pathways. However, these viruses are not complete carcinogens, and further alterations within the infected cells and in their microenvironment are necessary for tumor establishment and progression. Alterations in components of the extracellular matrix for instance, matrix metalloproteinases and some of their regulators such as tissue inhibitors of metalloproteinases, have been consistently reported in human papillomaviruses-associated diseases. Matrix metalloproteinases function by remodeling the extracellular matrix and alterations in their expression levels and/or activity are associated with pathological processes and clinical variables including local tumor invasion, metastasis, tumor relapse and overall patient prognosis and survival. In this review we present a summarized discussion on the current data concerning the impact of human papillomavirus infection on the activity and expression of extracellular matrix components. We further comment on the possibility of targeting extracellular matrix molecules in experimental treatment protocols.