Immune therapy for human papillomaviruses-related cancers

Human papillomaviruses(HPVs) are a large family of double strand DNA viruses comprising more than 180 types. Infection with HPV is very common and it is associated with benign and malignant proliferation of skin and squamous mucosae. Many HPVs, considered lowrisk such as HPV 6 and 11, produce warts; while highrisk viruses, such as HPVs 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, and 58, induce tumors. About 5% of all cancers in men and women are associated with HPV infection. Because there are not antiviral drugs for HPV infection, current therapies for low-risk HPV infections involve physical removal of the lesion by cryotherapy, trichloracetic acid, laser, or surgical removal. Surgical procedures are effective in the treatment of precancerous lesions, however after these procedures, many recurrences appear due to new re-infections, or to failure of the procedure to eliminate the HPV. In addition, HPV can inhibit recognition of malignant cellsby the immune system, leading to the development of cancer lesions. When this occurs, radiotherapy and chemotherapy are then used. Unfortunately, about 50% of the HPV-cancer patients still die. In the past decade, a better knowledge of the natural history of the virushost interaction and of the immune response against this viral infection has brought new therapeutic strategies geared to modulate the immune system to generate an efficient virus-specific cytotoxic response. Novel HPV protein-expressing vaccines have shown some significant clinical efficacy and systemic HPV-specific cytotoxic T cell responses. This review will describe the current status of the several therapeutic strategies used to treat HPV-induced lesions, and discuss the various new therapies now being tested.

Molecular Epidemiological Study on Prevalence of Human Papillomaviruses in Patients with Common Warts in Beijing Area

Objective To study the circulation, distribution, and genomic diversity of HPVs in common warts in Beijing area of China. Methods Forty eight patients with pathologically diagnosed common warts were screened for the presence of HPV with HPV type-specific PCR and direct sequencing analysis. The genomic diversity of HPVs prevalent in Chinese patients was analyzed based on LCR. Results Forty one （85.5%） samples were positive for HPV DNA, 13（31.7%）-HPV-57, 12（29.3%）-HPV-la, 7（17%）-HPV-27 and 5（12.2%）-HPV-2a. Four cases were infected with two different HPV types, two （4.9%） with HPV-la and HPV-27, one （2.4%） with HPV-1 and HPV-57 and one （2.4%） with HPV-27 and HPV-57. In contrast to the prevalence of single strain of novel HPV-57 variant and HPV-1 prototype, two HPV-2 and three HPV-27 novel variants were found to circulate in Beijing. Conclusion HPV-1, -2, -27 and -57 are predominantly prevalent in patients with common warts in Beijing.

Associated Factors with Vaccination among Girls Aged between (11) and (13) against Papillomaviruses in Koumpentoum Health District (Senegal)

Introduction: Cervical cancer can be prevented by early vaccination of young people against papillomaviruses and screening for precancerous lesions. After a successful pilot phase, vaccination coverage in the generalization phase is low. The aim of this study was to determine papillomavirus vaccination coverage and to identify associated factors. Methods: This was a cross-sectional, descriptive and analytical study conducted from (1st) to (31th) September (2020) in Koumpentoum district. After a literature review, we conducted two-stage cluster sampling and direct structured interviews. Socio-demographic characteristics, knowledge, attitudes, and practices of mothers or guardians about papillomaviruses vaccination were collected using a standardized questionnaire. Multiple logistic regression was used to estimate odds ratios. Results: A total of (228) mothers or guardians were interviewed. Coverage for the first dose was (44.74%) CI95% (38.17 - 51.44) compared to (25.88%) CI95% (19.52 - 31.17) for the second dose. Factors statistically and significantly associated with coverage of the first dose of papillomaviruses vaccine were instruction of mothers or guardians (OR = 5.62 (3.16 - 9.99);p 0.001), schooling of the young girls (OR = 4.1 (2.23 - 7.53);p 0.001), information on cervical cancer (OR = 18.97 (5.68 - 63.24);p 0.001), knowledge of risks factors (OR = 8.04 (4.41 - 14.63);p 0.001), information on papillomaviruses vaccine (ORa = 10.26 (1.69 - 62.23);p = 0.011), knowledge on vaccine target (OR = 17.11 (8.51 - 34.41);p 0.001), knowledge of schedule vaccine (ORa = 3.67 (1.2 - 22.51);p = 0.022), knowledge of prevention methods (OR = 26.86 (12.22 - 59.05);p 0.001), and to be favorable in expanded vaccination program in general (ORa = 18.71 (1.5 - 128.41];p = 0.02). Conclusion: Vaccination of young girls against papillomaviruses in Koumpentoum health district could be improved by comprehensive interpersonal communication with mothers and guardians about cervical cancer and its prevention.

Role of viruses in periodontitis:An extensive review of herpesviruses,human immunodeficiency virus,coronavirus-19,papillomavirus and hepatitis viruses

Periodontitis is the inflammation of the supporting structures around the dentition.Several microbial agents,mostly bacteria,have been identified as causative factors for periodontal disease.On the other hand,oral cavity is a rich reservoir for viruses since it contains a wide variety of cell types that can be targeted by viruses.Traditionally,the focus of research about the oral flora has been on bacteria because the most widespread oral diseases,like periodontitis and dental caries,are outcomes of bacterial infection.However,recently and especially after the emergence of coronavirus disease 2019,there is a growing tendency toward including viruses also into the scope of oral microbiome investigations.The global high prevalence of periodontitis and viral infections may point out to a concomitant or synergistic effect between the two.Although the exact nature of the mechanism still is not clearly understood,this could be speculated through the manipulation of the immune system by viruses;hence facilitating the furthermore colonization of the oral tissues by bacteria.This review provides an extensive and detailed update on the role of the most common viruses including herpes family(herpes simplex,varicella-zoster,Epstein-Barr,cytomegalovirus),Human papillomaviruses,Human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2 in the initiation,progression and prognosis of periodontitis.

Model systems to study the life cycle of human papillomaviruses and HPV-associated cancers

The prevalent human papillomaviruses(HPVs) infect either cutaneous or mucosal epithelium. Active Infections lead to epithelial hyperprolifeation and are usually cleared in healthy individuals within a year. Persistent infections in the anogenital tracts by certain high-risk genotypes such as HPV-16, HPV-18 and closely related types, can progress to high grade dysplasias and carcinomas in women and men, including cervical, vulva, penile and anal cancers. A significant fraction of the head and neck cancers are also caused by HPV-16. The viral oncogenes responsible for neoplastic conversion are E6 and E7 that disrupt the pathways controlled by the two major tumor suppressor genes, p53 and members of p RB family. Because HPV cannot be propagated in conventional submerged monolayer cell cultures, organotypic epithelial raft cultures that generate a stratified and differentiated epithelium have been used to study the viral life cycle. This article describes several systems to examine aspects of the viral productive phase, along with the advantages and limitations. Animal model systems of HPV carcinogenesis are also briefly described.

Traditional Chinese Medicine Erhuang Suppository for Treatment of Persistent High-risk Human Papillomavirus Infection and Its Impact on Transcriptome of Uterine Cervix

Objective High-risk human papillomavirus(HR-HPV)infection is the chief cause of cervical intraepithelial neoplasia(CIN)and cervical carcinoma.The Erhuang suppository(EHS)is a traditional Chinese medicine(TCM)prepared from realgar(As_(2)S_(2)),Coptidis rhizoma,alumen,and borneolum syntheticum and has been used for antiviral and antitumor purposes.However,whether EHS can efficiently alleviate HR-HPV infection remains unclear.This study was conducted to evaluate the efficacy of EHS for the treatment of persistent HR-HPV infection in the uterine cervix.Methods In this study,we evaluated the therapeutic efficacy of EHS in a randomized controlled clinical trial with a 3-month follow-up.Totally,70 patients with persistent HR-HPV infection were randomly assigned to receive intravaginal administration of EHS or placebo.HPV DNA,ThinPrep cytologic test(TCT),colposcopy,and safety evaluation were carried out after treatment.Microarray analysis was performed to compare transcriptome profiles before and after EHS treatment.A K14-HPV16 mouse model was generated to confirm the efficiency of EHS.Results After 3 months,74.3%(26/35)of the patients in the treatment group were HPV negative,compared to 6.9%(2/29)in the placebo group.High-throughput microarrays revealed distinct transcriptome profiles after treatment.The differentially expressed genes were significantly enriched in complement activation,immune response,and apoptotic processes.The K14-HPV16 mouse model also validated the remarkable efficacy of EHS.Conclusion This study demonstrated that EHS is effective against HR-HPV infection and cervical lesions.Additionally,no obvious systemic toxicity was observed in patients during the trial.The superior efficacy and safety of EHS demonstrated its considerable value as a potential cost-effective drug for the treatment of HPV infection and HPV-related cervical diseases.

Mother-to-Child Transmission of Human Papillomavirus in Burkina Faso

Introduction: Human papillomavirus (HPV) infection is the most widespread sexually transmitted infection in the world. Today, there is growing evidence that HPV can be transmitted early in life, and one potential route is mother-to-child transmission. Data on this route of HPV transmission are scarce in Africa and particularly in Burkina Faso, where no data on the subject are yet available. The aim of our study was to estimate the rate of mother-to-child transmission of HPV infection and to identify circulating genotypes. Methodology: Cervico-uterine samples were collected from 100 full-term pregnant women and, buccal samples were obtained from their newborns at Hopital Saint Camille de Ouagadougou (HOSCO) by the specialist physician. HPV DNA amplification and genotyping were performed by PCR followed by hybridization using the HPV Direct Flow Chips kit, detecting 36 genotypes including 18 high-risk and 18 low-risk. Results: The prevalence of HPV in newborns was 8% (8/100). Six (6) HPV-positive neonates had HPV-positive mothers, while 2 HPV-positive neonates had HPV-negative mothers. The vertical transmission rate was 26.09% (6/23). Mother-newborn genotypes were concordant. However, the genotype profile of the newborns was more restricted than that of the mothers. Conclusion: HPV DNA was found in 8% of newborns in our study. The genotype profile of the mother-newborn pair was concordant. Asymptomatic HPV infection in a pregnant woman could constitute a risk factor for vertical transmission.

HPV/HBV or HPV/HCV Co-Infections in Women Treated for Chronic Hepatitis at Hôpital Saint Camille in Ouagadougou, Burkina Faso

Introduction: Cervical cancer is a public health concern and is mainly caused by Human papillomaviruses (HPV). In many parts of the world, studies are being carried out to understand the different genotypes to better tackle this issue. We conducted a study to determine the prevalence of HPV genotypes in women with chronic hepatitis B or C infection, co-infected or not with HIV, treated at the Hôpital Saint Camille in Ouagadougou (Burkina Faso). Methods: This study was conducted from April to July 2023, including 100 women in gastroenterology at Hôpital Saint Camille. A questionnaire on their socio-demographic and life style was administrated;and endocervical samples were collected using sterile swabs and then sent to Centre of Biomolecular Research Pietro Annigoni (CERBA). HPV molecular detection and genotyping were performed by PCR and hybridization using the HPV Direct Flow Chips kit. Data were analysis using chi square test or Fischer’s exact test with a significance threshold for p Results: The prevalence of HPV infection was 28% (28/100) on the sample of women tested. The most frequent genotypes were HPV 52 (8.33%), followed by HPV 18 and 68 (6.25% each) for high-risk HPVs, and HPV 6, 44/55 and 62/81 (8.33% each) for low-risk HPVs. Conclusion: This study, the first of its kind in Burkina Faso on this group of the population, reveals that the most frequent genotypes found in this study are not included in the vaccine available in Burkina Faso (Gardasil®4).

Hysteroscopic cervical biopsy for women with persistent human papillomavirus infection after loop electrosurgical excision procedure: A case report

BACKGROUNDAlmost all cases of cervical cancer can be attributed to human papillomavirus(HPV) infection. The loop electrosurgical excision procedure (LEEP) is widelyused to treat HPV-mediated disease;thus, cervical cancer is highly preventable.However, LEEP does not necessarily clear HPV rapidly and may affect theaccuracy of the results of ThinPrep cytology test (TCT) and cervical biopsy due tothe formation of cervical scars.CASE SUMMARYA 40-year-old woman underwent LEEP for cervical intraepithelial neoplasia grade1 approximately 10 years ago. Subsequent standard cervical cancer screeningsuggested persistent HPV-52 infection, but TCT results were negative. Cervicalbiopsy under colposcopy was performed thrice over a 10-year period, yieldingnegative pathology results. She developed abnormal vaginal bleeding after sexualactivity, persisting for approximately 1 year, and underwent hysteroscopy in ourhospital. Histopathologic evaluation confirmed adenocarcinoma in situ of theuterine cervix.CONCLUSIONPatients with long-term persistent, high-risk HPV infection and negative pathologyresults of cervical biopsy after LEEP are at risk of cervical cancer. Hysteroscopicresection of cervical canal tissue is recommended as a supplement tocervical biopsy because it helps define the lesion site and may yield a pathologicdiagnosis.

New cheaper human papilloma virus mass screening strategy reduces cervical cancer incidence in Changsha city:A clinical trial

BACKGROUND Cervical cancer is the second leading cause of death in women worldwide,second only to breast cancer.Around 80%of women have been infected with human papillomavirus(HPV)in their lifetime.Early screening and treatment are effective means of preventing cervical cancer,but due to economic reasons,many parts of the world do not have free screening programs to protect women’s health.AIM To increase HPV cervical cancer screening in Changsha and reduce the incidence of cervical cancer.METHODS Cervical cancer screening included gynecological examination,vaginal secretion examination and HPV high-risk typing testing.Cervical cytology examination(ThinPrep cytology test)was performed for individuals who test positive for HPV types other than 16 and 18.Vaginal colposcopy examination was performed for HPV16 and 18 positive individuals,as well as for those who were positive for ThinPrep cytology test.If the results of vaginal colposcopy examination were abnormal,histopathological examination was performed.We conducted a cost-benefit analysis after 4 years.RESULTS From 2019 to 2022,523437 women aged 35-64 years in Changsha city were screened and 73313 were positive,with a 14%positive rate.The detection rate of precancerous lesions of cervical cancer was 0.6%and the detection rate of cervical cancer was 0.037%.Among 311212 patients who underwent two cancers examinations,the incidence rate was reduced by more than half in the second examination.The average screening cost per woman was 120 RMB.The average cost of detecting early cases was 10619 RMB,with an early detection cost coefficient of 0.083.CONCLUSION Our screening strategy was effective and cost-effective,making it valuable for early diagnosis and treatment of cervical cancer.It is worth promoting in economically limited areas.

A study on the cognitive status of human papillomavirus among adult males in Tianjin based on the health belief model

Background:To understand the health beliefs and knowledge of human papillomavirus among adult males in Tianjin.Methods:An online questionnaire survey was conducted from 18 January 2023 to 6 March 2023 using snowball sampling method.Analyze the health belief scores and human papillomavirus(HPV)and HPV vaccine knowledge scores of adult males in Tianjin,and analyze their influencing factors.Results:A total of 388 adult males in Tianjin were surveyed,with an average total score of 3.23±0.04 for their health beliefs.Among them,the average scores for perceived severity,perceived susceptibility,perceived impairment,perceived benefit,and self-efficacy were 3.41±1.05,2.37±1.20,2.96±1.00,3.51±0.90,and 3.36±1.08,respectively.Multiple linear regression analyses showed education was a factor influencing health beliefs.The average total score of knowledge is 64.09±15.62,with 277 people scoring above 60,and a pass rate of 71.4%.Through multiple linear regression analysis,education level,emotional status,whether disease testing has been done,and whether family and friends have been diagnosed with HPV positive are the main influencing factors.Conclusion:The awareness rate of HPV among adult males in Tianjin is still acceptable,but there are still misconceptions.The overall level of health beliefs is moderate,and the perceived susceptibility level is low.It is necessary to strengthen health education on HPV related knowledge for males and improve their cognitive level.

Prevalence of Precancerous Lesions Based on Digital Cervicography with VIA/VILI among Women Positive for High-Risk Human Papillomavirus Serotypes: A Screening Center-Based Study in Cameroon

Background: Since 2021, high-risk Human Papilloma Virus (HR-HPV) testing has been the recommended screening test for cervical cancer for all settings;either used alone in a “test and treat” strategy, or with a triage test, with or without biopsy, before treatment. Cameroon has rolled out immunization against HPV 16 and 18, but studies show a higher prevalence of non-16/18 HR-HPV types. Objectives: Determine the prevalence of precancerous lesions, in women with HR-HPV infection and evaluate association of digital cervicography (DC) VIA/VILI positivity with HPV serotype, as a measure of their contribution to precancer and cancer incidence. Methodology: The study was cross-sectional, descriptive, and analytic. It took place at the Etoug-Ebe and Ekoudoum Baptist Hospitals in Yaoundé, during the period April-September 2022. We reviewed the records of women screened for cervical cancer between February 2020 and December 2021 and evaluated the prevalence of lesions on digital cervicography (DC) with VIA/VILI for women positive for HR-HPV serotypes. The data were analyzed using SPSS version 20.0 for Windows. P values Results: We identified 315 cases with a positive HR-HPV deoxyribonucleic acid (DNA) test, 224 (71.1%) had a DC VIA/VILI triage test done. Of these, 30 (13.4%) women had a positive DC VIA/VILI, with five women (2.2%) having lesions suggestive of cancer. Out of 11 cases positive for HPV 16 alone, 05 (45.5%) had a positive DC VIA/VILI test. Of the 14 cases positive for HPV 18 alone, 03 (21.4%) had a positive VIA/VILI, meanwhile only 19 (10.7%) of the 177 cases positive for non-16/18 HPV had a positive VIA/VILI test. Conclusion: A high proportion of women (13.4%) with HR HPV had a positive DC VIA/VILI, with a significant proportion (2.2%) having lesions suggestive of invasive cervical cancer HR-HPV serotype was associated with DC VIA/VILI positivity;HPV 16 had the strongest association (45.5%), followed by HPV 18 (21.4%), and non-16/18 HR-HPV (10.7%), suggesting a decreasing order of oncogenicity.

The effect of HPV infection on mental health status in women

Human papillomavirus(HPV)infection is one of the most common sexually transmitted infections globally,and its close association with the development of cervical cancer has become a major public health concern.HPV infection not only leads to physical health problems,but also has an impact on a woman’s mental health,such as:severe anxiety,fear,depression,negativity,and other psychological distress.The purpose of this review is to systematically summarize the current knowledge on this topic and to explore its current development in accordance with the PRISMA guidelines.We can provide interventions that may alleviate or even eliminate psychological problems in women,depending on their psychological characteristics.A total of 82 records were included in the study,including 37 papers on the effect of HPV infection on the mental health status of women and 45 studies on the effect of implementing interventions on the mental health of patients with HPV infection.The results show that HPV infection can make women produce anxiety,depression,shame,low self-esteem and other negative psychological.However,active and proper medical treatment,psychological counseling and support,and strengthening health education have positive effects on HPV-infected women,and can promote the mental health of HPV-infected women.

Anal carcinoma-exploring the epidemiology,risk factors,pathophysiology,diagnosis,and treatment

Anal carcinoma is a relatively rare tumor that accounts for approximately 2%of gastrointestinal malignancies and less than 7%of anorectal cancers.Most anal tumors originate between the anorectal junction and the anal verge.Risk factors for the disease include human papillomavirus infection,human immunodeficiency virus,tobacco use,immunosuppression,female sex,and older age.The pathogenesis of anal carcinoma is believed to be linked to human papillomavirusrelated inflammation,leading to dysplasia and progression to cancer.Squamous cell carcinoma is the most common type of anal tumor,with an annual incidence of approximately 1 to 2 per 100000 persons.Treatment regarding anal cancer has emerged over time.However,chemoradiation therapy remains the mainstay approach for early localized disease.Patients with metastatic disease are treated with systemic therapy,and salvage surgery is reserved for disease recurrence following chemoradiation.This article aims to provide background information on the epidemiology,risk factors,pathology,diagnosis,and current trends in the management of anal cancer.Future directions are briefly discussed.

Health promotion and education proposal among Chinese female college students:eliminating cervical cancer is no longer a dream

Cervical cancer is a serious threat to women’s health.Persistent high-risk human papillomavirus(HPV)infection is a necessary factor for cervical cancer development and has become a serious public health threat to women.At present,young women have become a high-risk group for potential HPV infection.HPV vaccination is an effective method to prevent HPV infection and related diseases and is a primary preventive measure for HPV infection-related diseases.This study explores the influencing factors of female college students’willingness to receive HPV vaccination,their ability to understand college students’HPV awareness,their motivation for HPV vaccination,their behavioral skills related to HPV vaccination,their willingness to receive HPV vaccination and their vaccination rate.The aim of this study was to increase the HPV vaccination rate of Chinese female college students through health education programs and thus reduce the incidence of cervical cancer.

Study on the Correlation between Human Papillomavirus and Mycoplasma genitalium Combined with TCT Detection

Objective: This study aims to explore the correlation between human papillomavirus (HPV) and Mycoplasma genitalium (CT) combined with TCT detection in cervical cancer screening. Method: A cross-sectional study design was adopted, and a total of 609 women who came to seek medical treatment were recruited as the study subjects. Combination testing was evaluated on cervical cancer screening by testing the women for HPV, CT with TCT detection and analyzing the relationship of cervical lesions with HPV and CT infection. Results: The study results showed that 21.57% of the subjects were infected with both HPV and CT, and 48.42% of the cases had abnormal TCT results at the same time. Further data analysis showed that HPV infection was significantly associated with abnormal TCT outcomes (p < 0.05), suggesting a possible synergistic effect of the two infections in cervical lesions. The combined sensitivity and specificity of HPV, CT and TCT detection were 21.57% and 48.42%, respectively, which were significantly higher than that of single detection. Conclusion: In summary, the results of this study support the importance of combined HPV, CT, and TCT testing in cervical cancer screening, and propose the hypothesis that combined testing may improve screening effectiveness. However, further large sample studies are needed to confirm this conclusion and explore the prospects of combined testing in clinical practice.

The Condyloma Acuminatum’s Recurrence Can Be Reduced by Lesional Auto-Transplantation

Background: Condyloma acuminatum (CA), also known as a genital wart (GW), is a sexually transmitted disease caused by human papillomavirus (HPV). HPV lesions, recurrence tendency, and risk of malignant formation are primarily dependent on the person’s immunity level. GW recurrence is a major challenge in CA treatment. The aim of this study was to explore how lesional auto-transplantation (LT) can be used to treat CA and decrease its recurrence. Methods: We treated CA through the preparation and implantation of tissue from nine CA patients in our dermatology clinic. Transplantation of small pieces of HPV lesions to the subcutaneous fat of the inguinal region was carried out with the help of a simple surgical method under local anesthesia. Patients were followed up for six to eight months. We searched PubMed and the Web of Science for treatment options for CA to compare our treatment method recurrence rate with existing treatment options. Results: During three months of follow-up, seven patients experienced no recurrence of condyloma lesions, while two patients experienced recurrence of small lesions of condyloma acuminatum. The recurrence rate of CA once treated by auto-transplantation was relatively low compared to other CA treatment options. Conclusions: Transplantation of HPV lesions to the inguinal area reduces the recurrence rate in sexually active individuals. The 2/9 recurrence after implantation could be due to poor hygiene, sexual relationships or immune factors.

Evaluating the Association between Human Papillomavirus and Vulvar Cancer:A Comprehensive Analysis Using Bradford Hill Criteria

Background:The role of human papillomavirus(HPV)in the development of vulvar cancer(VC)has been widely studied,but findings have been inconsistent.Despite numerous meta-analyses exploring the potential link between HPV and VC,the association remains controversial due to inherent limitations in meta-analytic methods.Objectives:To address this controversy,the study aims to investigate the potential link between HPV and VC using the Bradford Hill criteria,which offer a more comprehensive framework for establishing causation.Methodology:The study began by extracting all relevant studies on the association between HPV and VC from the PubMed database.The potential links were then assessed by examining the data using the major postulates of the Bradford Hill criteria.To ensure the reliability of the findings,the methodologies of the identified studies were critically evaluated to account for possible false-negative and false-positive results.Results:The assessment of previous studies against the Bradford Hill criteria revealed that the major postulates were not fulfilled.Conclusion:Based on the findings,it can concluded that there is no causal association between HPV and VC.

DNA damage response is hijacked by human papillomaviruses to complete their life cycle

The DNA damage response （DDR） is activated when DNA is altered by intrinsic or extrinsic agents. This pathway is a complex signaling network and plays important roles in genome stability, tumor transformation, and cell cycle regulation. Human papillomaviruses （HPVs） are the main etiological agents of cervical cancer. Cervical cancer ranks as the fourth most common cancer among women and the second most frequent cause of cancer-related death worldwide. Over 200 types of HPVs have been identified and about one third of these infect the genital tract. The HPV life cycle is associated with epithelial differentiation. Recent studies have shown that HPVs deregulate the DDR to achieve a productive life cycle. In this review, I summarize current findings about how HPVs mediate the ataxia- telangiectasia mutated kinase （ATM） and the ATM- and RAD3-related kinase （ATR） DDRs, and focus on the roles that ATM and ATR signalings play in HPV viral replication. In addition, I demonstrate that the signal transducer and acti- vator of transcription-5 （STAT）-5, an important immune regulator, can promote ATM and ATR activations through different mechanisms. These findings may provide novel opportunities for development of new therapeutic targets for HPV-related cancers.

The role of human papillomaviruses in cancer progression

The importance of human papillomavirus(HPV)infection and its role in the progress of cancer have been widely evaluated.The understanding of HPV association with certain cancers,such as cervical cancer,is very well established.A big step forward in the prevention of HPV associated cancers with the use of early detection by screening strategies has also been taken.In the last decade,development of HPV vaccination has reduced the number of cases in HPV infections and infection induced cancers.In this report,we review the HPV pathogenesis and highlight the mechanism of HPV involvement in cancer development.