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Diseases associated with human papillomavirus infection
Abstract
Human papillomaviruses (HPVs) are ubiquitous, well adapted to their host and cleverly sequestered away from immune responses. HPV infections can be productive, subclinical or latent in both skin and mucosa. The causal association of HPV with cervical cancer, and increasingly with rising numbers of squamous cell carcinomas at other sites in both men and women, is increasingly recognised, while the morbidity of cutaneous HPV lesions, particularly in the immunosuppressed population is also significant. This chapter sets out the range of infections and clinical manifestations of the consequences of infection and its persistence and describes why HPVs are both highly effective pathogens and carcinogens, challenging to eliminate.
... For instance, the incidence rate of rectal cancer in men is approximately 4.3 per 100,000 compared to 3.2 per 100,000 in women [12]. These differences may be influenced by various factors, including hormonal differences, lifestyle factors, and differences in the uptake of screening [13]. ...
... E6 oncoprotein promotes the degradation of p53, a key regulator of the cell cycle and apoptosis. By inactivating p53, E6 prevents the cell from undergoing apoptosis in response to DNA damage, allowing the accumulation of genetic mutations [13]. E7 oncoprotein binds to pRb, releasing E2F transcription factors that drive the cell cycle forward, leading to uncontrolled cell division [13]. ...
... By inactivating p53, E6 prevents the cell from undergoing apoptosis in response to DNA damage, allowing the accumulation of genetic mutations [13]. E7 oncoprotein binds to pRb, releasing E2F transcription factors that drive the cell cycle forward, leading to uncontrolled cell division [13]. The combined action of E6 and E7 oncoproteins disrupts normal cell cycle control, promoting the development of cancer. ...
Human papillomavirus (HPV) is a significant etiological factor in the development of anal and rectal cancers. Despite preventive measures such as vaccination and screening, disparities in incidence and outcomes persist between genders. This chapter explores the intersection of HPV-related health behaviors, gender norms, and systemic resource and screening disparities for women. It examines the epidemiology of HPV, biological mechanisms of carcinogenesis, and health behaviors that mitigate cancer risk. A critical analysis of gender norms reveals how societal expectations influence health behaviors and access to care. The chapter concludes with strategies to improve screening rates and resource allocation, aiming to create a more equitable healthcare landscape.
... While plantar warts are more common in children and adolescents than in adults, they can occur at any age 1,[4][5][6][7] . ...
... However, it rarely occurs before the age of 5 years. The prevalence increases with age, reaching a peak distribution at 10~14 years 6 . Ghadgepatil et al. 5 reported that the second decade were the most common group with 40% of palmoplantar warts. ...
... Individuals in this age group are particularly susceptible to such skin lesions. They engaged in barefoot activities, which cause microtrauma of the skin and provide a risk of transmission 6,8 . This study also considers the second and third decades as the most affected age groups. ...
Background: Plantar wart is a common dermatologic disease encountered in outpatient clinics. Clinical trials for the treatment of plantar warts have been conducted, but only a few studies have focused on the epidemiological factors of plantar warts. Objective: This study aims to analyze the epidemiological factors for plantar warts in Korean individuals at a single institution. Methods: We retrospectively reviewed the electronic medical records of patients with plantar warts at Chosun University Hospital from January 2019 to December 2022. Results: A total of 176 patients were included in this retrospective study. Plantar warts are more common in younger ages, and men tend to have higher rates of plantar warts than women (M:F = 3:1). The patients showed a higher incidence of plantar warts during winter (29.0%), of which 74.4% were urban residents. 6.3% of patients had warts after trauma. Plantar warts were also observed in 66 of the 504 household members of the patients. The most common locations of wart lesions were in the forefoot (73.3%), followed by the toes (60.8%), midfoot (22.2%), and heel (18.2%). Moreover, the location of the lesions was almost equal, most often on the right side (34.7%), followed by the bilateral (33.5%) and left sides (31.8%). Conclusion: This study offers valuable information about the epidemiological factors of plantar warts in South Korea. These contents will be used for lifestyle education to prevent the recurrence of plantar warts.
... Cervical cancer is a major public health problem. It is a disease associated with persistent human papillomavirus (HPV) infection [1]. Around 89% of the 565,541 cases of cervical cancer reported worldwide in 2019 occurred in low-and middleincome countries [2]. ...
... Persistent infection with high-risk oncogenic HPV (HR HPV) is recognized as the main cause of cervical cancer [1], and HPV infection can disappear (clearance) within a few months. In fact, some 80-90% of HPV infections are transient, disappearing spontaneously within 24 months of first detection [13]. ...
... Cervical cancer is caused by many factors. However, the primary and necessary cause is human papillomavirus infection [1]. Human papillomaviruses or HPVs (Human PapillomaVirus) are small (around 60 nm in diameter) naked viruses (without envelopes) of the Papillomaviridae family. ...
In Burkina Faso, cervical cancer is the second most common cancer among women, and the second leading cause of cancer-related death. Both incidence and mortality rates have risen steadily in recent years. Its natural history is linked to persistent infection with an oncogenic human papillomavirus, a necessary but not sufficient factor in its development. However, cervical cancer is said to be preventable, due to its slow evolution. To date, it is the only cancer that can be prevented by vaccination against human papillomaviruses (HPV). Systematic and regular screening enables early detection of precancerous lesions so that they can be treated, thereby preventing the onset of cervical cancer. Unfortunately, access to these preventive measures remains limited for the majority of the population due to cost. The government of Burkina Faso, through its Ministry of Health, has put in place strategies to facilitate access to screening and care. Burkina Faso's researchers and teacher-researchers are also collaborating with traditional health practitioners in the search for better remedies and active substances with no side effects, through the use of medicinal plants. This review aims to take stock of cervical cancer in Burkina Faso: achievements, shortcomings, strategies implemented by the government and the contribution of scientific research to the fight against this scourge.
... Papillomaviruses are a broad group of non-enveloped DNA viruses that infect a wide variety of vertebrate species, including mammals, birds, reptiles, and fish [22,[36][37][38][39][40][41]. While many infections are asymptomatic, PVs can also cause benign epithelial growths [22,[37][38][39][40]. ...
... Papillomaviruses are a broad group of non-enveloped DNA viruses that infect a wide variety of vertebrate species, including mammals, birds, reptiles, and fish [22,[36][37][38][39][40][41]. While many infections are asymptomatic, PVs can also cause benign epithelial growths [22,[37][38][39][40]. In this study, we identified four complete genomes of novel papillomaviruses (OaPV1-4) with significant divergence from known sequences (48.90% to 51.22% nucleotide identity compared to axolotl papillomavirus), providing compelling evidence of evolutionary distinctiveness. ...
The platypus (Ornithorhynchus anatinus), a unique monotreme, represents a pivotal point in mammalian evolution with its distinctive traits, such as electroreception and venom production. Despite its evolutionary significance, the viral diversity within platypuses remains poorly understood. This study employed next-generation sequencing to investigate the virome of the dead platypuses, uncovering a range of novel and divergent viruses. Among the identified viruses were four complete genomes of papillomaviruses (OaPV1–4) exhibiting substantial divergence from known strains, suggesting a novel genus within the subfamily Secondpapillomavirinae. Additionally, five novel parvoviruses were detected, including two with complete genomes, highlighting the complex viral ecosystem of the platypus. Phylogenetic analysis placed these viruses in unique evolutionary branches, further demonstrating the platypus’s evolutionary significance. A circular DNA virus, a tombus-like virus, and a nodamuvirus were also identified, expanding the understanding of viral diversity in monotremes. These findings offer crucial insights into viral evolution in one of the most unique mammalian lineages, emphasising the need for further exploration to assess ecological and pathological impacts on platypus populations.
... The International HPV Reference Center classifies HPVs below the species level into new types that share less than 90% nucleotide identity in ORFL1 (> 90%) [13][14][15][16][17]. On January 23, 2024, 223 types of HPV were recognized, which are classified into two categories: high-risk oncogenic HPV (HPV-HR). Among the most common are types 16 and 18, described in 70% of cases of cervical cancer, and low-risk HPV (HPV-LR) (types 6 and 11 identified in 90% of genital condylomas and laryngeal papillomas) [14,18,19]. ...
... Among infected individuals, it is estimated that only 5% will present with some clinical manifestation, characterized predominantly by the appearance of condylomata acuminata (warts) in the genital areas, mouth, and throat in women and men. In the remainder there are no visible lesions, the individual does not present signs and symptoms but HPV is present [19]. In both situations, transmission of the virus is possible, which can ultimately culminate in the development of neoplasms including cervical, vaginal or vulvar cancer [12,[20][21][22][23][24][25]. ...
The objective of study was to characterize HPV in vaginal samples from women being seen at the Center for Reproductive Medicine and Infertility at Weill Cornell Medicine before and following ovarian stimulation. A total of 29 women made samples available for analysis by viral metagenomics. Eighteen women were HPV-positive, six (33.3%) at their initial visit and 15 (83.3%) following hormone stimulation (p = 0.0059). Pairwise comparison of nucleotide sequences and phylogenetic analysis showed the classification sequences into two genera: Alphapapillomavirus and Gammapapillomavirus. Sequences were from 8 HPV types: HPV 51 (n = 2), HPV 68 (n = 1), HPV 83 (n = 9), HPV 84 (n = 2), HPV 121 (n = 6), HPV 175 (n = 1) and HPV 190 (n = 1). Additionally, C16b and C30 likely represent new types. In summary, multiple HPV types are present in the vagina of reproductive age women and are induced by hormone used to stimulate ovulation.
... HPV infection can be advantageous to a diversity of skin lesions, from common warts to precancerous and cancerous lesions. In the context of the increasing incidence of these infections, prevention becomes indispensable to reduce the long-term impact of HPV on public health [50,52,55,64]. ...
... The HPV vaccine has demonstrated strong effectiveness in preventing high-risk HPV strain infections that are linked to the formation of skin lesions and various cancers in the anogenital and oropharyngeal regions [64][65][66][67][68][69][70][71]. HPV infection can lead to a multitude of skin lesions, from common to precancerous and cancerous lesions [72][73][74][75][76]. Prevention of high-risk HPV infections, which are associated with the formation of skin lesions and various types of cancer in the anogenital and oropharyngeal regions, is effectively achieved by available HPV vaccines such as Gardasil and Cervarix [77,78]. ...
This narrative review provides a comprehensive analysis of skin lesions caused by human papillomavirus (HPV). Human papillomavirus is an infection involving a virus that is omnipresent and can range from benign wart lesions to malignant skin growths. This review includes an analysis of the skin manifestations caused by HPV, and the need for continued successful diagnostic techniques and treatment methods, given the increasing rates of infection among people worldwide. We reviewed all 135 studies related to pathophysiology involving skin, risk factors, and early detection methods like biopsy and molecular testing, from 2000 to 2023. The current treatments, including cryotherapy and laser therapy, are discussed, while the review emphasizes the role of HPV vaccination in preventing infection. Recommendations for the future would involve the improvement of public education and increased vaccine coverage, together with innovative therapies toward better management or control of skin diseases associated with the human papillomavirus (HPV). By advancing these recommendations, we will be in a better position to prevent and treat HPV skin conditions, thus improving the health condition of the general public across the world.
... The HPVs are classified mainly into three classes, e.g. mucocutaneous, cutaneous, and the ones associated with the epidermodysplasia verruciformis (EV), a rare autosomal recessive disorder [6]. They can also be classified according to the site of infection in the body, e.g. ...
... They can also be classified according to the site of infection in the body, e.g. oral, external skin, and the anogenital regions [6]. Cervical cancer is the most common HPVrelated disease, with studies suggesting 99% of cervical cancers are caused by high-risk HPV infection [7]. ...
Human papillomaviruses (HPVs) are widespread, sexually transmitted group of viruses that infect most individuals at some stage, causing genital warts and cancers. They are members of the Papillomaviridae family, which contains about 400 HPV types. China is among the high HPV burden countries with reported infections of multiple HPV types, accounting for 17.3% of global deaths and 18.2% of global new cases. Thus, understanding the genetic variation and geographic diversity characteristics of HPVs isolated in China is critical for global HPV prevention strategies. Thus, we analyzed the available HPV genome sequences isolated in China that grouped into two categories (alpha-and gamma-papillomaviruses) based on full-length genomes. The most common were HPV-16, −6, −58, and −52 respectively. In addition, four of the novel strains isolated in China, e.g. TG550, JDFY01, CH2, and L55 clustered with the HPV-mSK 159, 244, 201, and 200 respectively. Our phylogeographic network analysis indicated that the L55, TG550, and CH2 are genetically identical to the mSK 200, 046, and 201 respectively, while JDFY01 appeared separately, connected to the mSK-040 following five mutational steps. Also, we found ten recombination events among HPV-6/11 types within their E1, E2, E7, L1/L2 proteins, and Long Control Region ORFs. We achieved the consensus amino acid sequences of HPV proteins and found a conserved stretch of amino acids within E5A of all HPVs circulating in China. These findings offer valued insights into the genetic relationships, distribution, and evolution of the HPVs in China that may assist in adapting effective HPV preventive measures.
... On the basis of its oncogenic potential, HPV can be divided into two different groups: high-risk and low-risk viruses. The former, which include the well-known types 16 and 18, have been classified as oncogenic to humans according to the International Agency for Research on Cancer [3] , and may cause neoplastic transformations in the following epithelial areas: cervical, vulvar, anogenital, penile and oropharyngeal [4] . The latter, such as types 6 and 11, are responsible for benign diseases such as genital warts [5] . ...
... The latter, such as types 6 and 11, are responsible for benign diseases such as genital warts [5] . The morbidity of cutaneous HPV lesions, particularly in immunosuppressed people [4] , also deserves to be mentioned. HPV infections are primarily contracted by direct contact of skin or mucosa with an infected lesion. ...
Human papilloma virus infection is a common sexually transmitted disease. In addition to its tropism for epithelial mucosae and skin, HPV can also infect the male urogenital tract and strongly bind the sperm head, causing a reduction of semen quality, with detrimental effects on both natural and assisted fertility. An association between HPV and assisted reproductive technology (ART) programs has been reported, and HPV infection of semen seems to have a negative influence on the outcome of these procedures. None of the standard procedures commonly used for sperm selection before ART showed efficacy in eliminating HPV from the sperm head. Several strategies have been suggested to improve viral clearance in semen of infertile patients, such as counseling and anti-HPV vaccination. Moreover, these strategies were able to increase the natural fertility of couples with HPV semen infection. Finally, a modified swim-up with the addition of an enzymatic treatment, despite reducing sperm motility, was reported to eliminate the virus from the sperm head. In this manuscript we propose a flow chart for the management of infertile couples with HPV semen infection. KEY WORDS: HPV, HPV semen infection, assisted reproductive techniques, HPV vaccines.
... Most of these studies have focused on bacteria and fungi, whereas little is known about the viral community [34][35][36][37] . PV are known to be part of the vaginal biota in several animal species 38,39 . Our study showed the presence of OaPV DNA in vaginal swabs of healthy mares, which has never been reported before. ...
There are four genotypes of ovine papillomaviruses (OaPVs): OaPV1, OaPV2, and OaPV4, which are ovine delta papillomaviruses responsible for epithelial and mesenchymal cell infections, and OaPV3, an epitheliotropic Dyokappapapillomavirus associated with cutaneous tumors in sheep, including squamous cell carcinoma. Vaginal swabs of healthy mares were evaluated for the presence of PVs to investigate whether the vaginal virobiota of asymptomatic mares harbored OaPVs. High-performance digital droplet polymerase chain reaction (ddPCR) was used to quantitatively detect OaPV types 1–4 DNA in 94 vaginal swabs collected at the National Reference Center for Veterinary and Comparative Oncology (CEROVEC), Genoa, Italy. All samples were comparatively evaluated for OaPV DNA loading using real-time quantitative PCR. ddPCR detected OaPV DNA in 25 vaginal swab samples (26.6%), whereas qPCR revealed 13 vaginal swabs (11.7%). Differences between the two molecular protocols were determined to be statistically significant using McNemar’s test (p < 0.0005). The detected OaPV types were OaPV1 and OaPV3. Both methods failed to detect OaPV2 or OaPV4 DNA, which could be attributed to the limited number of samples examined. OaPV1 is the most prevalent OaPV in equine vaginal virobiota . This study is the first to provide evidence of the presence of OaPV DNA in vaginal swabs of healthy mares. This comparative detection approach underscores the superior sensitivity of ddPCR over qPCR.
... Among the viruses found in the oral cavity, HPV has been linked to head and neck squamous cell carcinoma and is implicated in several oral diseases, such as papilloma, condylomas, and chronic skin or mucosal epithelial infections. HPV types 6, 11, and 16 are commonly associated with oral papillomas, while HPV type 2 is mostly responsible for benign warts [59]. ...
The human microbiome plays a vital role in maintaining human homeostasis, acting as a key regulator of host immunity and defense mechanisms. However, dysbiotic microbial communities may cause disruption of the symbiotic relationship between the host and the local microbiota, leading to the pathogenesis of various diseases, including viral infections and cancers. One of the most common infectious agents causing cancer is the human papilloma virus (HPV), which accounts for more than 90% of cervical cancers. In most cases, the host immune system is activated and clears HPV, whereas in some cases, the infection persists and can lead to precancerous lesions. Over the last two decades, the advent of next-generation sequencing (NGS) technology and bioinformatics has allowed a thorough and in-depth analysis of the microbial composition in various anatomical niches, allowing researchers to unveil the interactions and the underlying mechanisms through which the human microbiota could affect HPV infection establishment, persistence, and progression. Accordingly, the present narrative review aims to shed light on our understanding of the role of the human microbiome in the context of HPV infection and its progression, mainly to cervical cancer. Furthermore, we explore the mechanisms by which the composition and balance of microbial communities exert potential pathogenic or protective effects, leading to either HPV persistence and disease outcomes or clearance. Special interest is given to how the microbiome can modulate host immunity to HPV infection. Lastly, we summarize the latest findings on the therapeutic efficacy of probiotics and prebiotics in preventing and/or treating HPV infections and the potential of vaginal microbiota transplantation while highlighting the significance of personalized medicine approaches emerging from NGS-based microbiome profiling and artificial intelligence (AI) for the optimal management of HPV-related diseases.
... On the other hand, it can cause genital warts on the penis, scrotum, vagina, anus, hands, fingers, face, or legs. Also, some strains can cause some types of cancer and other diseases [4]. In most cases, the immune system defeats the HPV infection before it starts to form warts. ...
Human papillomavirus (HPV) is a sexually transmitted virus that causes cervical cancer in women and leads to death. In this research paper, we prepare a fractional mathematical model that contains a system of four fractional differential equations (FDEs) based on the Caputo operator to describe the most significant epidemiological features of HPV infection and how this infection is transmitted. To check this model’s well-posedness, we investigate solutions existence, positivity, uniqueness and boundedness. Additionally, we identify the disease-free and endemic equilibrium points (EPs) to introduce their local stability, and also bifurcation analysis is presented. To find out whether the infection is spreading among the population or not, we calculated the basic reproduction number () and accordingly we conducted a sensitivity analysis to determine the main epidemiological parameters controlling the proposed model. Further, the fractional optimal control problem (FOCP) is implemented for the proposed problem by utilizing Pontryagin’s maximum principle (PMP) with three time-dependent control variables, which are the efforts to promote safe sexual habits such as using a condom or monogamy, vaccination for HPV, and preventive measures for cervical cancer such as early screening and using drugs that prevent cells from turning cancerous. The necessary optimality conditions (NOCs) for this FOCP are established. Numerical simulations are carried out and presented in graphical representation to display the impact of combining different intervention optimal control strategies on the transmission dynamics of HPV. From the presented results, we confirm that all the proposed control measures help limit the spread of the disease to some extent, but the most effective strategy to eliminate the disease is to combine all control efforts.
... Virus particles liberated from the epithelium can spread person-to-person directly or indirectly through objects. [26] Results of the previous research about the environmental risks of acquiring warts are inconsistent. Moreover, almost all studies are cross-sectional, making it difficult to determine the precise causal influences of the risk variables. ...
... HPVs mainly target differentiating squamous epithelium cells. In females, its impact also causes uterine cancer [3]. In contrast, LRHPVs have less affinity to the p53 and pRb proteins [4]. ...
... Nearly all sexually active individuals are expected to contract the virus at some point in their lifetime [2,3]. Although most HPV infections are temporary and benign, with about 70% clearing within a year and over 90% resolving within two years, some infections can persist [4]. These persistent infections greatly increase the likelihood of developing several types of cancer. ...
Background and aim
Human papillomavirus (HPV) is a major contributor to sexually transmitted infections, especially common in sexually active populations. Although the majority of HPV infections resolve naturally, certain cases can develop into different types of cancer. This study focused on evaluating the prevalence and distribution of HPV genotypes across males and females of different age groups who visited a laboratory in Urmia, Iran.
Materials and methods
Samples from the genital area were obtained from participants in the study. DNA extraction was performed using the Favorgen extraction kit (Favorgen, Taiwan), followed by genotyping through Real-Time PCR. Genotypes were determined using the MehrViru HPV genotyping kit (MehrViru, Iran). Additionally, demographic details, including age, were analyzed in conjunction with the statistical virological data.
Results
Between 2022 and 2023, a total of 447 individuals, including both referred and routine visitors, attended the laboratory, comprising 431 females and 16 males. Of these, 195 tested positive for HPV, resulting in an overall prevalence rate of 43.6%. Among the positive cases, 90 individuals (46.2%) were infected with a single HPV genotype, while 105 cases (53.8%) had multiple genotype infections. The most common genotypes identified were HPV-6 (41.0%), HPV-16 (15.4%), HPV-56 (10.8%), and HPV-90 (10.8%). The least genotype identified was HPV-43, which was detected in 5 cases (2.6%). Additionally, our analysis revealed that women under 30 who tested positive were predominantly infected with the LR genotype, a pattern also seen in the four men in the same age group, all of whom were infected with the LR genotype.
Conclusion
Our findings underscore the significant presence of HPV among both females and males visiting the laboratory in Urmia, particularly in individuals under 30 years old. The identification of HPV-6 and HPV-16 as the most prevalent genotypes highlights the importance of age-specific intervention strategies. Although vaccination programs cover HPV-6 and HPV-16, HPV-56 is not included, which underscores the need for comprehensive screening and preventive measures to address the potential long-term impacts of HPV-related diseases.
... The changes observed in the tissue include a disorganized granular layer with the presence of koilocytic cells and parakeratotic cells with nuclear inclusions in more superficial layers [5]. The clinical changes in the natural appearance of the tissue can play a key role, along with the symptoms associated with the lesions, in the decision to seek medical assistance to restore healthy skin. ...
Background: Plantar warts, caused by the human papillomavirus (HPV), are a common skin condition characterized by painful lesions on the soles of the feet. These lesions can significantly impact skin appearance, quality of life, and, in severe cases, mobility. Traditional treatment methods, such as chemical cauterization or pharmaceutical therapies, are often painful and require multiple visits to achieve complete wart removal and skin regeneration. This study aims to assess the clinical effectiveness of the needling technique as an alternative treatment. This method involves repeatedly puncturing the lesion under local anesthesia or posterior tibial nerve block to trigger an immune response and promote wart clearance. Methods: A total of 26 patients underwent the needling procedure, which included puncturing the wart under local anesthesia, followed by wound dressing and topical application of iodopovidone to facilitate scab formation. Follow-up visits were scheduled until full wart resolution was observed. Analgesics were provided for moderate pain management when necessary. Results: After 30 days, a success rate of 57.7% was achieved. Patients reported mild pain, which subsided within a few days, and expressed high levels of satisfaction with the treatment outcome. Conclusions: The needling technique emerges as an effective alternative to chemical treatments, offering a notable wart clearance rate. Its use under local anesthesia enhances patient comfort and reduces treatment-associated anxiety compared to conventional therapies.
... HPVs are the most common sexually transmitted infections (STIs) worldwide, affecting epithelial cells in areas such as the cervix, anus, throat, and genital regions [7]. While many HPV infections are harmless and resolve on their own, some strains can lead to serious health issues, including genital warts, respiratory papillomatosis, and various cancers, such as cervical, anal, and oropharyngeal cancers [8]. Certain high-risk HPV strains, particularly HPV-16 and HPV-18, are known for their carcinogenic potential and are associated with most cervical cancers and other anogenital malignancies [9]. ...
The number of new cancer cases is soaring, and currently, there are 440.5 per 100,000 new cases reported every year. A quarter of these are related to human papillomavirus (HPV) infections, particularly types 16 and 18. These include oropharyngeal, anal, vaginal, and penile cancers. A critical aspect of their oncogenic potential lies in their ability to manipulate host immune responses, facilitating immune evasion and carcinogenesis. High-risk HPVs target key immune components like granzymes A and B and MHC-I, which are crucial for the elimination of virus-infected and transformed cells, thereby weakening immune surveillance. Evidence suggests that high-risk HPVs downregulate the expression of tumor suppressors, such as p53 and pRB, and the activity of these immune components, weakening CTL and NK cell responses, thus enabling persistent infection and carcinogenesis. We discuss the implications of granzyme and MHC-I dysregulation for immune evasion, tumor progression, and potential therapeutic strategies. This review further explores the regulation of granzyme A, B, and MHC-I by high-risk HPVs, focusing on how viral oncoproteins, E6 and E7, interfere with granzyme-mediated cytotoxicity and antigen presentation. The complex interplay between high-risk HPVs, granzyme A, granzyme B, and MHC-I may provide insights into novel approaches for targeting HPV-associated cancers.
... Infection with high-risk human papillomavirus (HPV) is a major risk factor for cervical cancer [1,2]. About 99.7% of cervical cancer cases are caused by persistent high-risk HPV infections [3], with HPV16/18 infections contributing to 70-75% of cervical cancer cases worldwide [4] and 40-60% of precancerous lesions [5]. Nevertheless, clinical epidemiologic studies have also reported that approximately 5% of cervical cancers are not associated with persistent HPV infection [6], and in particular, some cervical adenocarcinomas are not associated with HPV infection [7]. ...
Background
Persistent infection with high-risk human papillomavirus (HPV) is a significant risk factor for cervical cancer. HPV typing and cytology are conducted in women of appropriate age to assess the risk of cervical lesions and to guide the need for further diagnostic procedures such as colposcopy, cervical biopsy, or treatment. This article explores methods to predict the risks of high-grade precancerous cervical lesions based on high-risk HPV typing.
Methods
We conducted a retrospective analysis of HPV typing data from 158,565 women, including 19,707 who underwent ThinPrep cytologic testing (TCT), 7,539 who had colposcopy examinations, and 4,762 who had biopsies. We evaluated the sensitivity, specificity, and risk parameters of high-grade lesions associated with high-risk HPV types.
Results
(1) The overall prevalence of HPV infection was 17.89%, with the most prevalent types being HPV52 (4.44%), HPV58 (2.10%), HPV53 (1.96%), HPV81 (1.85%), HPV42 (1.75%), and HPV16 (1.44%). (2) The sensitivity and specificity of detecting high-grade lesions in TCT, colposcopy, and biopsy, based on high-risk HPV typing, demonstrated a strong linear correlation with the infection rate of each type. (3) HPV16 was confirmed to have a higher risk of CIN2 + in biopsies using a self-defined risk parameter. (4) The top five HPV types with the highest PPVs and pathogenicity risks in biopsies were HPV45, HPV16, HPV58, HPV33, and HPV18.
Conclusion
In Changsha, China, HPV52, HPV58, and HPV53 were the most prevalent and contributed significantly to high-grade lesions. After adjusting for infection rates, a self-defined risk parameter was proposed as a measure of the intrinsic risks of high-grade lesions associated with high-risk HPV types. Focused monitoring of prevalent high-risk HPV types such as HPV45, HPV16, HPV58, HPV33, and HPV18, which show the highest pathogenicity risks, is recommended in our region.
... With the advancement of viral metagenomics, an increasing number of complete genomes of papillomaviruses (PVs) have been identified in a wide range of organisms (1)(2)(3). PVs can infect the mucous membranes and squamous epithelium of vertebrates including fish, birds, reptiles, mammals, and even humans, often causing subclinical lesions and benign proliferations (4)(5)(6). In severe cases, some of them have potential to transform into malignant tumors, making PVs a continuing concern for both human and animal health even though it is highly specific (7). ...
To fully characterize papillomavirus diversity in giant pandas (Ailuropoda melanoleuca), we identified a novel papillomavirus (named AmPV5, GenBank accession number MZ357114) in oral swabs from giant pandas with the help of viral metagenomics technology in this study. The complete circular genome of AmPV5 is 7,935 bp in length, with a GC content of 39.1%. It encodes five early genes (E1, E2, E4, E6, and E7), two late genes (L1 and L2), and features conserved zinc-binding domains (CXXC- (X)28/29-CXXC) in E6 and E7 genes. E7 protein has an LxCxE domain (pRB binding) in its N-terminal region. The nucleotide sequence of AmPV5 L1 gene shares < 70% identity with other related sequences available in the GenBank database. Phylogenetic analysis indicated that AmPV5 fell within the Lambdapapillomavirus genus but formed a monophyletic branch away from other papillomaviruses found in Ailuropoda melanoleuca, Canis, Felis catus, Panthera uncia, Enhydra lutris, and Procyon lotor. According to the International Committee on Taxonomy of Viruses (ICTV) classification guidelines, AmPV5 is classified as a new species within the Lambdapapillomavirus genus. The discovery provides valuable insights into the viral diversity in giant pandas and highlights the need for continued surveillance of wildlife pathogens. Future studies should explore the potential role of AmPV5 in the health and disease ecology of this endangered species.
... However, this confirms the possibility of HPV 72 in oral infection and not just in anogenital infection where it causes external warts. [35] The fourth genotype identified in this study is HPV JEB2. This is a taxonomically unclassified type with partial L1 reference sequence. ...
... PVs infect the epithelial and mucosal cells of many animal hosts, such as birds, fish, reptiles, dogs, cats, bovines, and other domestic and wild mammals [12][13][14][15][16]. Most papillomavirus infections are asymptomatic, but some types are associated with lesions and even cancers [17]. Human papillomaviruses (HPVs) have more than 230 genotypes, some of which are carcinogenic and responsible for 4.5% of all human cancers [18]. ...
Bats are mammals with high biodiversity and wide geographical range. In Brazil, three haematophagous bat species are found. Desmodus rotundus is the most documented due to its role as a primary host of rabies virus in Latin America. Bats are known to harbor various emerging viruses causing severe human diseases. Beyond zoonotic viruses, these animals also harbor a diversity of non-zoonotic viruses. Papillomaviruses are circular double-stranded deoxyribonucleic acid (dsDNA) viruses that infect the epithelial and mucosal cells of many vertebrates, occasionally causing malignant lesions. High-throughput sequencing has enabled papillomaviruses discovery in different bat species. Here, 22 D. rotundus samples were collected through the rabies eradication program in Rio Grande do Sul. The DNA extracted from pooled intestines was amplified by the rolling-circle amplification (RCA) method and sequenced using the Illumina® MiSeq platform (San Diego, CA, USA).Analysis revealed three contigs corresponding to the Papillomaviridae family, representing three novel viruses named DrPV-1, DrPV-2, and DrPV-3. Phylogenetic analysis suggests DrPV-1 may constitute a new species within the Dyophipapillomavirus genus, while DrPV-2 and DrPV-3 may represent different types within the same species from a novel genus. This is the first description of a papillomavirus in the D. rotundus species, contributing to the characterization of PVs in the Chiropteran order.
... These inflammatory mediators not only promote cell proliferation and survival but also foster genomic instability and genetic mutations, predisposing cells to malignant transformation [17]. Moreover, chronic inflammation mediated by viral infections can disrupt tissue homeostasis, impair immune surveillance, and create an immunosuppressive microenvironment conducive to tumor evasion and immune escape [18]. The interplay between viral factors, host immune responses, and the surrounding stromal cells orchestrates a dynamic and complex TME that influences tumor behavior and therapeutic responses [19]. ...
Viral infections are a significant factor in the etiology of various cancers, with the tumor microenvironment (TME) playing a crucial role in disease progression. This review delves into the complex interactions between viruses and the TME, highlighting how these interactions shape the course of viral cancers. We explore the distinct roles of immune cells, including T-cells, B-cells, macrophages, and dendritic cells, within the TME and their influence on cancer progression. The review also examines how viral oncoproteins manipulate the TME to promote immune evasion and tumor survival. Unraveling these mechanisms highlights the emerging paradigm of targeting the TME as a novel approach to cancer treatment. Our analysis provides insights into the dynamic interplay between viruses and the TME, offering a roadmap for innovative treatments that leverage the unique characteristics of viral cancers.
... Highrisk HPV targets differentiating squamous epithelial tissues of digestive and urogenital systems, leading to corresponding cancer types, with uterine cervix cancer being the most common. Unsafe sexual relationships are a primary risk factor for viral transmission [27]. While sexual contact is a common mode of transmission, HPV has been found in the placental, blood, and reproductive cells of individuals without sexual activity [28]. ...
Human papillomaviruses (HPVs) contribute to 5% of cancers, yet there is a lack of specific antiviral agents targeting HPV infection. Antiviral peptides (AVPs) present a promising alternative to conventional therapeutics. This study aims to explore the use of AVPs against the HPV16 E6 oncoprotein through virtual screening. The potential binding pocket of the E6 oncoprotein was determined, and using the antimicrobial CAMPR4 database 18 AVPs were shortlisted. These AVPs were then docked to the E6 oncoprotein using the HawkDock server, followed by dynamic simulation. Among the AVPs tested, AVP18, AVP10, and AVP7 demonstrated the highest inhibitory potential against the E6 oncoprotein. AVP18 exhibited more non-bonded contacts, hydrogen bonds, and electrostatic forces. Dynamics simulation confirmed the stability of the complexes formed by these top AVPs with E6. This research suggests that AVP7, AVP10, and AVP18 are promising lead candidates for blocking HPV16 by inhibiting the E6 oncoprotein. Keywords: antiviral peptides, docking, dynamics simulation, E6 oncoprotein, human papillomavirus
... In the case of immunosuppressed patients, other types such as HPV 75, 76, and 77 have also been detected in the lesions. It should be noticed that many types can be detected per lesion, most commonly in the subjects with an impaired immune system [40]. ...
Introduction: Viral infections cause oxygen deprivation, leading to hypoxia or anoxia in certain tissues. The limitation of mitochondrial respiration is one of the major events during hypoxia that induces alternative metabolic activities and increased levels of certain biomolecules such as nitric oxide (NO) metabolites. In this study, we aimed to investigate the role of NO metabolites and hypoxia in HPV infection. Materials and Methods: We included 36 patients with palmoplantar warts and 36 healthy subjects and performed serum determinations of NO metabolites (direct nitrite, total nitrite, nitrate, and 3-nitrotyrosine) and HIF1α, a marker of hypoxia. Results: We found elevated serum levels in NO metabolites and HIF1α, and decreased direct nitrite/nitrate ratios in patients with warts versus controls. Additionally, we identified statistically significant positive correlations between NO metabolites and HIF1α levels, except for 3-nitrotyrosine. Conclusions: Our findings show that HPV infection causes hypoxia and alterations in NO metabolism and suggest a link between wart development and cellular stress. Our research could provide new insights for a comprehensive understanding of the pathogenesis of cutaneous HPV infections.
... About 70% of HPV infections diminish on their own within one year and 90% heal within two years. The remaining cases experience the development of tenacious infections in throat, mouth, anus, the epithelial cells and mucosal tissues of the cervix and penis that has the capability to culminate into serious illnesses [2,3]. Some HPV strains pose a higher risk of causing cancer compared to others. ...
This study introduces a novel stochastic SICR (susceptible, infected, cervical cancer and recovered) model to illustrate HPV (Human papillomavirus) infection dynamics and its impact on cervical cancer in the female population of India. We prove the existence of a unique positive global solution that ensures stochastic boundedness and permanence. Moreover, sufficient conditions for HPV extinction are established through the stochastic extinction parameter
, indicating that the infection will die out if
. Conversely, the persistence of HPV is established by the existence and uniqueness of an ergodic stationary distribution of the solution when the stochastic threshold
, using the suitable selection of Lyapunov functions. Furthermore, data on cervical cancer cases in India from 2016 to 2020 is fitted to the model, providing parameter values suitable for the region. The theoretical findings are validated using the Positive-Preserving Truncated Euler–Maruyama method. Additionally, effective control strategies for India are suggested based on model predictions and sensitivity of key parameters.
... Human Papillomavirus (HPV) is a common viral infection that affects epithelial cells, with over 200 identified types and some of them are associated with various cancers and other diseases [1]. HPV is primarily transmitted through sexual contact, and certain high-risk types, such as HPV- 16 [4,5]. ...
Our study described the phased implementation of HPV vaccination programs targeting adolescent girls and next expansion efforts, which achieved high coverage rates in pilot areas through school-based and health center-based strategies. Despite these successes, the overall vaccination uptake remains low with the barriers such as financial constraints, logistical difficulties, and cultural barriers. Clinical trials have confirmed the vaccine's high efficacy and safety, consistent with global data. Key advancements in the program include leveraging school infrastructure for vaccine delivery and integrating the HPV vaccine into the National Expanded Program on Immunization. Effective communication strategies and robust community engagement have been pivotal in addressing misconceptions and increasing acceptance. During this literature review, we systematically searched for scientific articles and related documents from online databases such as PubMed, Scopus, and Google Scholar, selecting studies related to the development and implementation of HPV vaccines in Vietnam. Articles lacking sufficient data or relevance to the research topic were excluded. In the future, continued efforts should focus on sustainable funding, public awareness, and logistical improvements to enhance vaccine accessibility, particularly in remote regions. International partnerships and adherence to global best practices are also crucial for further progress. This review underscores the urgent need for comprehensive strategies to mitigate HPV-related disease burdens in Vietnam, offering valuable insights for global public health initiatives
... At present, more than 200 HPV genotypes have been identified [1]. Over 99% of cervical cancers contain HPV DNA, and the proportion related to specific high-risk human papillomavirus (HR-HPV) types varies geographically and ethnically [2]. HR-HPV is classified into 15 types (HPV16, 18,21,33,35,39,45,51,52,56,58,59,68,73 and 82), among which HPV16 and HPV18 are two of the most prevalent types and account for about 70% of all HPV related cervical cancers [3]. ...
Background
High-risk human papillomavirus (HR-HPV) infection is an important factor for the development of cervical cancer. HPV18 is the second most common HR-HPV after HPV16.
Methods
In this study, MEGA11 software was used to analyze the variation and phylogenetic tree of HPV18 E6-E7 and L1 genes. The selective pressure to E6, E7 and L1 genes was estimated using pamlX. In addition, the B cell epitopes of L1 amino acid sequences and T cell epitopes of E6-E7 amino acid sequences in HPV18 were predicted by ABCpred server and IEDB website, respectively.
Results
A total of 9 single nucleotide variants were found in E6-E7 sequences, of which 2 were nonsynonymous variants and 7 were synonymous variants. Twenty single nucleotide variants were identified in L1 sequence, including 11 nonsynonymous variants and 9 synonymous variants. Phylogenetic analysis showed that E6-E7 and L1 sequences were all distributed in A lineage. In HPV18 E6, E7 and L1 sequences, no positively selected site was found. The nonconservative substitution R545C in L1 affected hypothetical B cell epitope. Two nonconservative substitutions, S82A in E6, and R53Q in E7, impacted multiple hypothetical T cell epitopes.
Conclusion
The sequence variation data of HPV18 may lay a foundation for the virus diagnosis, further study of cervical cancer and vaccine design in central China.
... They are non-enveloped with double-stranded circular DNA. There are over 200 types of HPV that have been identified and classified into 29 genera, most of which affect humans [3,4]. The DNA of HPV is comprised of around eight open reading frames (ORFs). ...
Human Papillomavirus (HPV) is an oncogenic virus that primarily causes premalignant and malignant cervical lesions particularly infection with high-risk types of viruses. Cervical cancer (CC) is a common gynecological tumor, ranking second in the female reproductive system tumor, particularly in women from developing countries. The prevalent and genotyping of high-risk HPV among Iraqi women during various stages of cervical lesions and cervical cancer were examined by using a real-time PCR. Results of this work revealed that the prevalence of HPV infection in women suffering from gynecological problem was 43%. The distribution of the high-risk HPV was relatively high for both HR-HPV-16 (44.90%) and HR-HPV-39 (14.29%), with HR-HPV-16 is being the most common. The finding of this study can be used to manage HPV infection and cervical cancer particularly at earlier stages of cervical lesions.
... squamous intraepithelial lesions (precancerous), which are the precursors to preinvasive cervical intraepithelial neoplasia (CIN grades 1, 2, and 3), and the progression to invasive CC. 4,5,7 The likelihood that genital HPVs will function as carcinogens in the emergence of CC has been categorized based on the degree of the link with the disease. HPV types 6, 11, 42, 43, 44, 54, 61, 70, 72, and 81 are low-risk types while types 16,18,31,33,35,39,45,51,52,56,58,59,66,68,73, and 82 are high-risk or oncogenic types. ...
Background and Aims
Human papillomavirus (HPV) infections that continue to exist are the main cause of cervical cancer (CC), two‐thirds of CC occurrences worldwide are caused by HPV 16 and HPV 18, and 99.7% of CC tumors are linked to oncogenic HPV infection. To identify challenges of CC and its prevention and treatment modalities.
Methods
This review examined the epidemiology, predisposing factors, genetic factors, clinical assessment methods, current treatment options, and prevention approaches for CC. We had perform a narrative data synthesis rather than a pooled analysis. A thorough literature search in pertinent databases related to CC was done with the inclusion of data that were published in the English language.
Results
Early detection of CC is of utmost importance to detect precancerous lesions at an early stage. Therefore, all responsible agencies concerned with health should make all women aware of the benefits of CC screening and educate the general public. HPV vaccination coverage is very low in resource‐limited settings.
Conclusion
To achieve the goal of eliminating CC as a public health problem in 2030, the World Health Organization will pay special attention to increasing HPV vaccination coverage throughout the world. To further improve HPV vaccine acceptability among parents and their children, safety‐related aspects of the HPV vaccine should be further investigated through post‐marketing surveillance and multicentre randomized clinical trials.
... 1 Mucosotropic HPVs can be subdivided into low-risk HPV (lrHPV) and high-risk HPV (hrHPV), depending on their degree of association with human malignancy. 1 In the anogenital region, lrHPV are mainly associated with common, flat plane, anogenital warts, while hrHPV are mainly associated with cervical dysplasia and cancer in women. 2 Several sociobehavioral, environmental, and host genetic factors that are associated with the risk of lrHPV and hrHPV infections have been identified. Inflammatory factors also play critical roles in the immune response to HPV infections. ...
PURPOSE
Inflammatory mediators are important regulators of immune response and can modulate the inflammation caused by viral infections, including human papillomavirus (HPV). In this study, we evaluated the association between cervical immune mediators, including chemokines, cytokines, and growth factors with HPV infections.
MATERIALS AND METHODS
We used a nonmagnetic bead–based multiplex assay to determine 27 immune mediators in cervical secretions collected from 275 women in a prospective longitudinal cohort design. All the study participants were age 18 years or older, had a history of vaginal sexual intercourse, were not currently pregnant, and had no history of cervical disease or hysterectomy.
RESULTS
The mean (±standard deviation) age of the participants was 41 (±8) years, and about half (51% [141/275]) were HPV-positive, of whom 7% (10/141) had low-risk HPV (lrHPV), 61% (86/141) had high-risk HPV (hrHPV), and 32% (45/141) had both lrHPV and hrHPV infections. Higher concentrations of some immune mediators were associated with HPV infections, including eotaxin, interferon-gamma, interleukin (IL)-1β, IL-2, IL-4, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, macrophage inflammatory protein (MIP)-1α, MIP-1β, regulated upon activation normal T-cell expressed and secreted (RANTES), and tumor necrosis factor (TNF)-α and any HPV; IL-2, IL-4, IL-5, IL-7, IL-10, IL-12p70, and IL-13 and lrHPV; and eotaxin, interferon, IL-1B, IL-4, IL-7, IL-8, IL-9, IL-10, IL-13, IL-15, MIP-1α, MIP-1β, RANTES, TNF-α concentrations, and hrHPV infections. Higher concentrations of granulocyte macrophage colony-stimulating factor, IL-1 receptor antagonist (IL-1Ra), and monocyte chemotactic protein-1 (MCP-1) were associated with reduced odds of any HPV, while IL-1Ra and MCP-1 were associated with reduced odds of hrHPV infections.
CONCLUSION
Several chemokines, cytokines, and growth factors are associated with group-specific HPV infections in this population of women. These important findings contribute to the understanding of the immune response to HPV, cytokine profiles and their potential implications for cervical pathogenesis, and can guide future research in this field.
... Human papillomaviruses have been established as a pivotal etiological factor not only for all cervical cancers but also for a substantial fraction of other human malignancies [34][35][36][37]. While the majority of HPV infections are transient and resolve asymptomatically, with the immune system usually eradicating the virus, persistent infections with HPV pose a significant risk. ...
... We also observed that the cells were not able to recover their normal proliferation rate since this effect was more noticeable at the end of the analysis at 6 days compared to the control cells. This is a relevant result because the HPV type of the HeLa cells (HPV 18) is observed in more aggressive and faster-evolving cervical cancer [33]. This proliferationdecreasing effect resembles that of overexpression of the tumor suppressor protein MAGI1 in glioma cancer cell lines, a very aggressive cancer. ...
Background
TheSLC5A8 gene is silenced in various types of cancer, including cervical cancer; we recently demonstrated that the SLC5A8 gene is also silenced in cervical cancer by hypermethylation of the CpG island in the gene promoter. This study aims to analyze whether SLC5A8 could be a tumor suppressor in cervical cancer.
Methods
After ectopic expressing SLC5A8 in the HeLa cell line, we evaluated its effects on cell behavior both in vitro and in vivo by Confocal immunofluorescence, cell proliferation, migration assays, and xenograft transplants.
Results
Overexpression of SLC5A8 in the HeLa cell line decreased its proliferation by arresting cancer cells in the G1 phase and inhibiting cellular migration. Furthermore, we observed that pyruvate increased the SLC5A8 effect, inducing S-phase arrest and inhibiting the entry into mitosis. SLC5A8 decreased tumor growth in xenograft transplants, significantly reducing the volume and tumor weight at 35 days of analysis.
Conclusions
In summary, our results indicate that SLC5A8 has a role as a tumor suppressor in cervical cancer.
... Human papillomaviruses have been established as a pivotal etiological factor not only for all cervical cancers but also for a substantial fraction of other human malignancies [34][35][36][37]. While the majority of HPV infections are transient and resolve asymptomatically, with the immune system usually eradicating the virus, persistent infections with HPV pose a significant risk. ...
... In most infected people, HPV is eliminated via the immune system [2]. In some cases, the virus may persist and cause symptomatic or subclinical skin or mucosal lesions [3]. The lesions can be benign. ...
Perianal skin tags are defined as soft growths that develop in the perianal region. Perianal skin tags commonly develop in patients with chronic anal fissures or following the healing of anal fissures and thrombosed external hemorrhoids. Perianal skin tags are not contagious and cannot be transmitted through sexual contact. Perianal warts can develop secondary to infection or virus such as human papillomavirus (HPV). Genital warts are considered the most common sexually transmitted disease (STD). This chapter discusses the difference between anal warts and skin tags, their etiology, clinical features and treatment.
The protective effect of naturally acquired humoral immunity against human papillomavirus (HPV) infection remains unclear. To investigate the role of infection‐induced antibodies on HPV detection in heterosexual partners, we used data from 392 unvaccinated couples (females aged 18–25 years attended up to six visits over 2 years; males aged 17–37 years attended up to two visits 4 months apart) enrolled (2005–2011) in Montreal. Genital and blood samples were HPV DNA genotyped and tested for L1 antibody titers of 14 HPV genotypes. Analyses considered female‐HPV units ( n = 4914 based on 351 couples) and male‐HPV units ( n = 4214 based on 301 couples); each female and male, respectively, contributed up to 14 observations corresponding to 14 genotypes. Modified Cox and logistic regressions estimated hazard and odds ratios (HR/OR) and 95% confidence intervals (CIs) for genotype‐specific HPV detections by partner serostatus (high/low: ≥/< baseline median antibody titers, 392 couples). There were 919 and 231 cumulative HPV detections among female‐HPV and male‐HPV units, respectively. Risk of HPV detections in females (HR = 1.05, CI: 0.90–1.22) and males (OR = 1.31, CI: 0.97–1.77) was similar between those with partners of high versus low serostatus. Constraining to baseline HPV‐negative participants with HPV‐positive partners yielded unchanged results. This lack of association suggests that naturally developed HPV antibodies do not protect sexual partners from infection.
Human papillomavirus 16 and human papillomavirus 18 have been associated with different life-threatening cancers, including cervical, lung, penal, vulval, vaginal, anal, and oropharyngeal cancers, while cervical cancer is the most prominent one. Several research studies have suggested that the oncoproteins E6 and E7 are the leading cause of cancers associated with the human papillomavirus infection. Therefore, we developed two mRNA vaccines (V1 and V2) targeting these oncoproteins. We used several bioinformatics tools to predict helper T lymphocyte, cytotoxic T lymphocyte, and B-cell epitopes derived from the proteins and assessed their antigenicity, allergenicity, and toxicity. Both vaccines were constructed using selected epitopes, linkers, and adjuvants. After that, the vaccines were applied for physicochemical properties, secondary and tertiary structure predictions, and subsequent docking and simulation analyses. Accordingly, vaccine 1 (V1) and vaccine 2 (V2) showed better hydrophilicity with the grand average hydropathicity score of -0.811 and -0.648, respectively. The secondary and tertiary structures of the vaccines were also deemed satisfactory, with high stability indicated by the Ramachandran plot (V1:94.5% and V2:87.1%) and Z scores (V1: -5.15 and V2: -4.1). Docking analysis revealed substantial affinity of the vaccines towards the toll-like receptor-2 (V1: -1159.3, V2: -1246.3) and toll-like receptor-4 (V1: -1109.3, V2: -1244.8) receptors. Molecular dynamic simulation validated structural integrity and indicated varying stability throughout the simulation. Codon optimization showed significant expression of the vaccines (V1:51.88% and V2:51.63%) in E. coli vectors. Furthermore, regarding immune stimulation, the vaccines elicited significant B-cell and T-cell responses, including sustained adaptive and innate immune responses. Finally, thermodynamic predictions indicated stable mRNA structures of the vaccines (V1: -502.60 kcal/mol and V2: -450.90 kcal/mol). The proposed vaccines designed effectively targeting human papillomavirus oncoproteins have demonstrated promising results via robust immune responses, suggesting their suitability for further clinical advancement, including in vitro and in vivo experiments.
Human papillomavirus (HPV) is a pervasive sexually transmitted infection associated with various cancers, including cervical, anogenital, and oropharyngeal carcinomas. While the majority of HPV infections are transient and self-limiting, persistent infections with high-risk HPV strains play a critical role in carcinogenesis. Herein, the current knowledge on HPV’s involvement in cancer, the pivotal role of the tumor microenvironment in HPV-related malignancies, and the emerging potential of organoid models in research and therapeutic development were reviewed.
A comprehensive analysis of recent studies and advances in the field was conducted based on Google Scholar, PubMed, and Web of Science searching, focusing on the interaction between HPV and the tumor microenvironment and the application of organoid technology.
The tumor microenvironment significantly influences the growth and progression of cancers linked to HPV. Organoid models have shown to be useful resources for researching HPV-driven carcinogenesis.
Organoid technology’s application in HPV research enhances understanding of tumor microenvironment function, paving the way for specialized treatments and improved management of HPV-associated cancers.
HPV is a prevalent virus associated with a number of malignancies. Scientists are gaining a better understanding of the development of HPV-related malignancies and how they could be treated through new study employing 3D models called organoids. This review emphasizes how crucial these models are to advancing cancer therapy.
Introduction: Human papillomavirus (HPV) causes the most prevalent sexually transmitted infection. It is the most important cause of cervical cancer. The present study aimed to determine the prevalence of HPV infection and HPV genotypes in the recordings of patients referred to Dr. Sharifi Medical Laboratory in Isfahan, central Iran. Materials and Methods In a retrospective study, the HPV PCR and genotyping results of 5643 patients including 4999 (88.6%) females and 644 (11.4%) males from May 2012 to August 2024 were studied. The available demographics, sex and age, were also recorded and analyzed. Results Of 5643 studied patient, 888 (15.7%) were HPV-positive. Genotype 6 was the most prevalent (9.1%), and genotypes 30 and 71 were the least prevalent (0.017%) identified genotypes. Out of 888, 470 (47.1%) and 418 (52.9%) were high-risk and low-risk HPV genotypes, respectively. HPV 16 was the most prevalent among high-risk genotypes followed by HPV 53 and 18. The HPV infection was significantly higher in patients under 20 years old and also in females compared to males. Conclusion Based on the results of the present study, the rate of HPV infection in Isfahan is close to that of most other regions in Iran. The prevalence of HPV infection with low- and high-risk genotypes was both higher in women. High-risk genotypes caused the majority of infections. Younger ages were the most at-risk group for the infection.
Human Papilloma virus (HPV) role has now been widely accepted as a causative agent for cervical as well as head and neck squamous cell carcinomas. Screening and early detection of cervical cancer remains the key element to eradicate this deadly disease. Since it has a long natural history and disease progression, this gave an opportunity for early detection through screening of precancerous lesions which was adopted in high income countries (HIC) like UK which has led to the significant reduction of the cases. Unfortunately, Low- and middle-income countries are facing huge burden because of the lack of effective screening program. FDA approved Cervarix, Gardasil and Gardasil 9 are used as prophylaxis for cervical cancer & genital warts but screening is still essential after vaccination because these vaccines are not effective against all types of HPV types. HPV 16 & HPV 18 are highly oncogenic types and accounts for 70% of cervical cancers. The use of vaccine reduces the risk of getting HPV infection and decrease the rate of morbidity and mortality due to the cervical cancer. In addition to vaccines, many peptides or protein-based & cell or DNA-based vaccines are still in clinical trials; these prevention and management available in vaccines are likely to come up with significant benefits of health in future. Although it’s usually cured by immune system but presence of certain cofactors such as smoking, HIV etc. reduces the probability of an individual to eradicate the infection effectively. The aim of this study is to review literature regarding HPV related infections and malignancies. Moreover, it will make individuals aware about prophylaxis & treatment options available for HPV infection. This review article evaluates the HPV related diseases, there screening, evaluation and management currently available. Bangladesh Journal of Medical Science Vol. 23 No. 04 October’24 Page : 967-983
Se estudió la infección por Virus del Papiloma Humano (VPH), genotipos circulantes y variantes intratípicas en 320 mujeres con lesiones citológicas y cáncer cervicouterino (CaCU), residentes en la región Litoral del Ecuador; y su relación con variables virales, clínico-epidemiológicas y sociodemográficas entre 2012 y 2015. Se realizó la detección del VPH con iniciadores universales MY09/MY11, genotipado mediante el sistema comercial Anyplex™II HPV28 y filogenia de variantes virales. Resultó una frecuencia de infección del 94% (300/320), predominio de tipos oncogénicos y 92% (276/330) de coinfecciones. Los VPH58, 70, 53, 35 y 16 fueron más frecuentes. De las secuencias de VPH16, el 69% (29/42) se agrupó con el linaje A y el resto con el D. Las 15 secuencias del VPH58 correspondieron al linaje A. El VPH16, en infecciones simples o en coinfecciones se asoció a lesiones de alto grado y CaCU. Las mujeres con nivel educacional básico, solteras, obreras, con inicio precoz de las relaciones sexuales tuvieron mayor probabilidad de infección viral (p<0,05). Aunque el VPH58 fue el más prevalente, no se asoció al CaCU, a menos que estuviera coinfectando con VPH16. La elevada frecuencia de VPH58 y de variantes más oncogénicas de VPH16 indica la necesidad de intensificar el programa de detección precoz del CaCU y fortalecer el programa de vacunación.
High-risk HPV infection accounts for 99.7% of cervical cancer, over 90% of anal cancer, 50% of head and neck cancers, 40% of vulvar cancer, and some cases of vaginal and penile cancer, contributing to approximately 5% of cancers worldwide. The development of cancer is a complex, multi-step process characterized by dysregulation of signaling pathways and alterations in metabolic pathways. Extensive research has demonstrated that metabolic reprogramming plays a key role in the progression of various cancers, such as cervical, head and neck, bladder, and prostate cancers, providing the material and energy foundation for rapid proliferation and migration of cancer cells. Metabolic reprogramming of tumor cells allows for the rapid generation of ATP, aiding in meeting the high energy demands of HPV-related cancer cell proliferation. The interaction between Human Papillomavirus (HPV) and its associated cancers has become a recent focus of investigation. The impact of HPV on cellular metabolism has emerged as an emerging research topic. A significant body of research has shown that HPV influences relevant metabolic signaling pathways, leading to cellular metabolic alterations. Exploring the underlying mechanisms may facilitate the discovery of biomarkers for diagnosis and treatment of HPV-associated diseases. In this review, we introduced the molecular structure of HPV and its replication process, discussed the diseases associated with HPV infection, described the energy metabolism of normal cells, highlighted the metabolic features of tumor cells, and provided an overview of recent advances in potential therapeutic targets that act on cellular metabolism. We discussed the potential mechanisms underlying these changes. This article aims to elucidate the role of Human Papillomavirus (HPV) in reshaping cellular metabolism and the application of metabolic changes in the research of related diseases. Targeting cancer metabolism may serve as an effective strategy to support traditional cancer treatments, as metabolic reprogramming is crucial for malignant transformation in cancer.
Many significant viral infections have been recorded in human history, which have caused enormous negative impacts worldwide. Human‐virus protein‐protein interactions (PPIs) mediate viral infection and immune processes in the host. The identification, quantification, localization, and construction of human‐virus PPIs maps are critical prerequisites for understanding the biophysical basis of the viral invasion process and characterising the framework for all protein functions. With the technological revolution and the introduction of artificial intelligence, the human‐virus PPIs maps have been expanded rapidly in the past decade and shed light on solving complicated biomedical problems. However, there is still a lack of prospective insight into the field. In this work, we comprehensively review and compare the effectiveness, potential, and limitations of diverse approaches for constructing large‐scale PPIs maps in human‐virus, including experimental methods based on biophysics and biochemistry, databases of human‐virus PPIs, computational methods based on artificial intelligence, and tools for visualising PPIs maps. The work aims to provide a toolbox for researchers, hoping to better assist in deciphering the relationship between humans and viruses.
To assess factors associated with concomitant anal and cervical human papillomavirus (HPV) infections in HIV-infected and at-risk women.
A study nested within the Women's Interagency HIV Study (WIHS), a multicenter longitudinal study of HIV-1 infection in women conducted in six centers within the United States.
Four hundred and seventy HIV-infected and 185 HIV-uninfected WIHS participants were interviewed and examined with anal and cervical cytology testing. Exfoliated cervical and anal specimens were assessed for HPV using PCR and type-specific HPV testing. Women with abnormal cytologic results had colposcopy or anoscopy-guided biopsy of visible lesions. Logistic regression analyses were performed and odds ratios (ORs) measured the association for concomitant anal and cervical HPV infection.
One hundred and sixty-three (42%) HIV-infected women had detectable anal and cervical HPV infection compared with 12 (8%) of the HIV-uninfected women (P < 0.001). HIV-infected women were more likely to have the same human papillomavirus (HPV) genotype in the anus and cervix than HIV-uninfected women (18 vs. 3%, P < 0.001). This was true for both oncogenic (9 vs. 2%, P = 0.003) and nononcogenic (12 vs. 1%, P < 0.001) HPV types. In multivariable analysis, the strongest factor associated with both oncogenic and nononcogenic concomitant HPV infection was being HIV-infected (OR = 4.6 and OR = 16.9, respectively). In multivariable analysis of HIV-infected women, CD4 cell count of less than 200 was the strongest factor associated with concomitant oncogenic (OR = 4.2) and nononcogenic (OR = 16.5) HPV infection.
HIV-infected women, particularly those women with low CD4 cell counts, may be good candidates for HPV screening and monitoring for both cervical and anal disease.
Background The American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI),
and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updates on cancer
incidence and death rates and trends in these outcomes for the United States. This year’s report includes incidence trends
for human papillomavirus (HPV)–associated cancers and HPV vaccination (recommended for adolescents aged 11–12 years).
Background
Wolfsburg HPV Epidemiological Study (WOLVES) is a population-based cohort study on HPV infections and associated diseases in the pre-vaccination era in young women in Wolfsburg, Germany.
Methods
Women born 1983/84 or 1988/89 were invited to participate. Participants were recruited in gynecology practices, and completed a questionnaire with socioeconomic, sexual and medical data including vaccination status. Pelvic examination with Pap smear and HPV testing (HC2 = Hybrid Capture 2) was obligatory. HC2-positive and 10% of HC2-negative samples were tested for specific HPV types with SPF-10-PCR, and in inconclusive cases with DNA sequencing. Women with genital warts (GW) and those with atypical Pap smears were transferred for colposcopy. GWs were classified as typical condylomata acuminata (TCA), flat condyloma (FC) and seborrheic wart-like (SWL).
Results
In total, 1258 subjects were recruited from the target population of 2850 (44.1%). Overall the prevalence of HC2 low-risk (LR) types was 8.5%. HPV6 was the most frequent LR type (2.1%), followed by HPV42 (1.1%), HPV11 and HPV44 (each 0.4%). LiPA showed a low sensitivity for HPV types 42, 90 and 91, which were detected only by HC2 and HPV sequencing. Nine women (0.7%) were transferred with incident GW: five TCA, two FC and two SWL. All TCA were associated with HPV6 in corresponding cervical swabs and warts. Tissues of SWL contained HPV6 (n = 1) and HPV16 (n = 1). The cumulative life-risk for GW was 1.4% in the 1988/89 and 4.8% in the 1983/84 cohort. Eight of 107 HC2-LR + and five of nine cases of GW had concomitant abnormal Pap smears. All CIN lesions could be linked to high-risk HPV types but borderline and low-grade abnormal smears were explained by vaginal and cervical TCA in four cases.
Conclusions
HC2 was a specific test for the detection of established and potential LR types. In this first WOLVES analysis, HPV6 was the most frequent HPV type and the single LR type linked to disease. The observed GW incidence of 715 per 100,000 fits well with estimates of healthcare providers. Although life risks for GW were lower than in Scandinavian analyses, the societal burden within the WOLVES populations was considerable.
Abstract Background Vulvar cancer is a relatively rare malignancy, which occurs most often in postmenopausal women. We have previously identified a geographic cluster of vulvar cancer in young Indigenous women living in remote communities in the Arnhem Land region of Australia. In this population, we investigated the prevalence of oncogenic human papillomavirus (HPV) infection in anogenital samples (vulvar/vaginal/perianal area and cervix) and compared the overall, type-specific and multiple infection prevalence between sites. Methods A cross-sectional survey of 551 Indigenous women aged 18–60 years was undertaken in 9 Arnhem Land communities. Women were consented for HPV detection and genotyping collected by a combined vulvar/vaginal/perianal (VVP) sweep swab and a separate PreservCyt endocervical sample collected during Pap cytology screening. HPV DNA testing was undertaken using PCR with broad spectrum L1 consensus PGMY09/11 primers with genotyping of positive samples by Roche Linear Array. The primary outcomes were the prevalence of cervical and VVP high-risk (HR) HPV. Results The prevalence of VVP HR-HPV was 39%, which was significantly higher than the cervical HR-HPV prevalence (26%, p
Background
Human papillomavirus (HPV) is well known as the major etiological agent for ano-genital cancer. In contrast to cervical cancer, anal cancer is uncommon, but is increasing steadily in the community over the last few decades. However, it has undergone an exponential rise in the men who have sex with men (MSM) and HIV + groups. HIV + MSM in particular, have anal cancer incidences about three times that of the highest worldwide reported cervical cancer incidences.
Discussion
There has therefore traditionally been a lack of data from studies focused on heterosexual men and non-HIV + women. There is also less evidence reporting on the putative precursor lesion to anal cancer (AIN – anal intraepithelial neoplasia), when compared to cervical cancer and CIN (cervical intraepithelial neoplasia). This review summarises the available biological and epidemiological evidence for HPV in the anal site and the pathogenesis of AIN and anal cancer amongst traditionally non-high risk groups.
Summary
There is strong evidence to conclude that high-grade AIN is a precursor to anal cancer, and some data on the progression of AIN to invasive cancer.
Background Although new HPV vaccines have been developed and are in the process of implementation, anogenital warts remain a very frequent problem in clinical practice.
Objective We wished to update previously published European guidelines for the management of anogenital warts.
Methods We performed a systematic review of randomized controlled trials for anogenital warts. The primary data were analyzed and collated, and the findings were formulated within the structure of a clinical guideline. The IUSTI Europe Editorial Board reviewed the draft guideline which was also posted on the web for comments which we incorporated into the final version of the guideline.
Results The data confirm that only surgical therapies have primary clearance rates approaching 100%. Recurrences, including new lesions at previously treated or new sites, occur after all therapies, and rates are often 20–30% or more. All therapies are associated with local skin reactions including itching, burning, erosions and pain.
Conclusions Physicians treating patients with genital warts should develop their own treatment algorithms which include local practice and recommendations. Such patient level management protocols should incorporate medical review of cases at least every 4 weeks, with switching of treatments if an inadequate response is observed. First episode patients should be offered sexually transmitted disease screening. Management should include partner notification and health promotion.
Recurrent respiratory papillomatosis (RRP), which is caused exclusively by human papilloma virus (HPV), is a rare condition characterized by recurrent growth of benign papillomata in the respiratory tract. The papillomata can occur anywhere in the aerodigestive tract but most frequently in the larynx, affecting both children and adults. The management of this entity remains still challenging since no specific definitive treatment exists. Nevertheless, novel surgical interventions as well as several adjuvant therapies have shown promising results in the long-term palliative management of this debilitating disease. Despite its mostly benign nature, RRP may cause significant morbidity and mortality because of its unpredictable clinical course and especially its tendency, albeit infrequent, for malignant transformation. In this article, we present two patients with RRP; one underwent bronchoscopic laser ablation in combination with inhaled interferon-alpha administration that led to a long-term regression of the disease while the other patient was diagnosed with transformation to squamous cell lung carcinoma with fatal outcome. We include a review of the current literature with special emphasis on RRP management and the potential role of HPV in the development of lung cancer.
Human papillomavirus (HPV) in oral carcinoma (OSCC) and potentially malignant disorders (OPMD) is controversial. The primary aim was to calculate pooled risk estimates for the association of HPV with OSCC and OPMD when compared with healthy oral mucosa as controls. We also examined the effects of sampling techniques on HPV detection rates.
Systematic review was performed using PubMed (January 1966-September 2010) and EMBASE (January 1990-September 2010). Eligible studies included randomized controlled, cohort and cross-sectional studies. Pooled data were analysed by calculating odds ratios, using a random effects model. Risk of bias was based on characteristics of study group, appropriateness of the control group and prospective design.
Of the 1121 publications identified, 39 cross-sectional studies met the inclusion criteria. Collectively, 1885 cases and 2248 controls of OSCC and 956 cases and 675 controls of OPMD were available for analysis. Significant association was found between pooled HPV-DNA detection and OSCC (OR = 3.98; 95% CI: 2.62-6.02) and even for HPV16 only (OR = 3.86; 95% CI: 2.16-6.86). HPV was also associated with OPMD (OR = 3.87; 95% CI: 2.87-5.21). In a subgroup analysis of OPMD, HPV was also associated with oral leukoplakia (OR = 4.03; 95% CI: 2.34-6.92), oral lichen planus (OR = 5.12; 95% CI: 2.40-10.93), and epithelial dysplasia (OR = 5.10; 95% CI: 2.03-12.80).
The results suggest a potentially important causal association between HPV and OSCC and OPMD.
HPV infection in the genital tract is common in young sexually active individuals, the majority of whom clear the infection without overt clinical disease. However most of those who develop benign lesions eventually mount an effective cell mediated immune (CMI) response and the lesions regress.
Failure to develop effective CMI to clear or control infection results in persistent infection and, in the case of the oncogenic HPVs, an increased probability of progression to CIN3 and invasive carcinoma. The prolonged duration of infection associated with HPV seems to be associated with effective evasion of innate immunity thus delaying the activation of adaptive immunity.
Natural infections in animals show that neutralising antibody to the virus coat protein L1 is protective suggesting that this would be an effective prophylactic vaccine strategy. The current prophylactic HPV VLP vaccines are delivered i.m. circumventing the intra-epithelial immune evasion strategies. These vaccines generate high levels of antibody and both serological and B cell memory as evidenced by persistence of antibody and robust recall responses. However there is no immune correlate - no antibody level that correlates with protection. Recent data on how HPV infects basal epithelial cells and how antibody can prevent this provides a mechanistic explanation for the effectiveness of HPV VLP vaccines.
We present an expansion of the classification of the family Papillomaviridae, which now contains 29 genera formed by 189 papillomavirus (PV) types isolated from humans (120 types), non-human mammals, birds and reptiles (64, 3 and 2 types, respectively). To accommodate the number of PV genera exceeding the Greek alphabet, the prefix "dyo" is used, continuing after the Omega-PVs with Dyodelta-PVs. The current set of human PVs is contained within five genera, whereas mammalian, avian and reptile PVs are contained within 20, 3 and 1 genera, respectively. We propose standardizations to the names of a number of animal PVs. As prerequisite for a coherent nomenclature of animal PVs, we propose founding a reference center for animal PVs. We discuss that based on emerging species concepts derived from genome sequences, PV types could be promoted to the taxonomic level of species, but we do not recommend implementing this change at the current time.
HPV infection in the genital tract is common in young sexually active individuals, the majority of whom clear the infection without overt clinical disease. However most of those who develop benign lesions eventually mount an effective cell mediated immune response and the lesions regress. Regression of ano-genital warts is accompanied histologically by a CD4+ T cell dominated Th1 response; animal models support this and provide evidence that the response is modulated by CD4+ T cell dependent mechanisms. Failure to develop effective CMI to clear or control infection results in persistent infection and, in the case of the oncogenic HPVs, an increased probability of progression to CIN3 and invasive carcinoma. The central importance of the CD4+ T cell population in the control of HPV infection is shown by the increased prevalence of HPV infections and HGSIL in individuals immunosuppressed as a consequence of HIV infection. The prolonged duration of infection associated with HPV seems to be associated with effective evasion of innate immunity as reflected in the absence of inflammation during virus replication, assembly and release, and down regulation of interferon secretion and response thus delaying the activation of adaptive immunity. Serum neutralising antibody to the major capsid protein L1 usually develops after the induction of successful cell mediated immunity and these antibody and cell mediated responses are protective against subsequent viral challenge in natural infections in animals. Prophylactic vaccines consisting of HPV L1 VLPs generate high anti L1 serum neutralizing antibody concentrations and in clinical trials have shown greater than 95 per cent efficacy against both benign and neoplastic genital HPV associated disease. These vaccines are delivered intramuscularly and therefore circumvent the immune evasion strategies of the virus.
The incidence of head and neck squamous cell carcinoma (HNSCC) has been gradually increasing over the last three decades. Recent data have now attributed a viral aetiology to a subset of head and neck cancers. Several studies indicate that oral human papillomavirus (HPV) infection is likely to be sexually acquired. The dominance of HPV 16 in HPV+ HNSCC is even greater than that seen in cervical carcinoma of total worldwide cases. Strong evidence suggests that HPV+ status is an important prognostic factor associated with a favourable outcome in head and neck cancers.
Approximately 30 to 40% of HNSCC patients with present with early stage I/II disease. These patients are treated with curative intent using single modality treatments either radiation or surgery alone. A non-operative approach is favored for patients in which surgery followed by either radiation alone or radiochemotherapy may lead to severe functional impairment. Cetuximab, a humanized mouse anti-EGFR IgG1 monoclonal antibody, improved locoregional control and overall survival in combination with radiotherapy in locally advanced tumours but at the cost of some increased cardiac morbidity and mortality.
Finally, the improved prognosis and treatment responses to chemotherapy and radiotherapy by HPV+ tumours may suggest that HPV status detection is required to better plan and individualize patient treatment regimes.
Infections by human papillomaviruses (HPVs) are the most frequently occurring sexually transmitted diseases. The crucial role of genital oncogenic HPV in cervical carcinoma development is now well established. In contrast, the role of cutaneous HPV in skin cancer development remains a matter of debate. Cutaneous beta-HPV strains show an amazing ubiquity. The fact that a few oncogenic genotypes cause cancers in patients suffering from epidermodysplasia verruciformis is in sharp contrast to the unapparent course of infection in the general population. Our recent investigations revealed that a natural barrier exists in humans, which protects them against infection with these papillomaviruses. A central role in the function of this HPV-specific barrier is played by a complex of the zinc-transporting proteins EVER1, EVER2, and ZnT-1, which maintain cellular zinc homeostasis. Apparently, the deregulation of the cellular zinc balance emerges as an important step in the life cycles not only of cutaneous but also of genital HPVs, although the latter viruses have developed a mechanism by which they can break the barrier and impose a zinc imbalance. Herein, we present a previously unpublished list of the cellular partners of EVER proteins, which points to future directions concerning investigations of the mechanisms of action of the EVER/ZnT-1 complex. We also present a general overview of the pathogenesis of HPV infections, taking into account the latest discoveries regarding the role of cellular zinc homeostasis in the HPV life cycle. We propose a potential model for the mechanism of function of the anti-HPV barrier.
To assess the relative risk of perinatal mortality, severe preterm delivery, and low birth weight associated with previous treatment for precursors of cervical cancer.
Medline and Embase citation tracking from January 1960 to December 2007. Selection criteria Eligible studies had data on severe pregnancy outcomes for women with and without previous treatment for cervical intraepithelial neoplasia. Considered outcomes were perinatal mortality, severe preterm delivery (<32/34 weeks), extreme preterm delivery (<28/30 weeks), and low birth weight (<2000 g, <1500 g, and <1000 g). Excisional and ablative treatment procedures were distinguished.
One prospective cohort and 19 retrospective studies were retrieved. Cold knife conisation was associated with a significantly increased risk of perinatal mortality (relative risk 2.87, 95% confidence interval 1.42 to 5.81) and a significantly higher risk of severe preterm delivery (2.78, 1.72 to 4.51), extreme preterm delivery (5.33, 1.63 to 17.40), and low birth weight of <2000 g (2.86, 1.37 to 5.97). Laser conisation, described in only one study, was also followed by a significantly increased chance of low birth weight of <2000 g and <1500 g. Large loop excision of the transformation zone and ablative treatment with cryotherapy or laser were not associated with a significantly increased risk of serious adverse pregnancy outcomes. Ablation by radical diathermy was associated with a significantly higher frequency of perinatal mortality, severe and extreme preterm delivery, and low birth weight below 2000 g or 1500 g.
In the treatment of cervical intraepithelial neoplasia, cold knife conisation and probably both laser conisation and radical diathermy are associated with an increased risk of subsequent perinatal mortality and other serious pregnancy outcomes, unlike laser ablation and cryotherapy. Large loop excision of the transformation zone cannot be considered as completely free of adverse outcomes.
Epidermodysplasia verruciformis (EV) is a rare, autosomal recessive genodermatosis associated with a high risk of skin carcinoma (MIM 226400). EV is characterized by the abnormal susceptibility of otherwise healthy patients to infection by specific, weakly virulent human papillomaviruses (HPVs), including the potentially oncogenic HPV-5. Inactivating mutations in either of the related EVER1/TMC6 and EVER2/TMC8 genes cause most EV cases. New insights in EV pathogenesis have been gained from the following recent observations: (1) EV-specific HPVs (betapapillomaviruses) are defective for an important growth-promoting function encoded by an E5/E8 gene present in other HPVs, and inactivation of EVER proteins may compensate for the missing viral function; (2) the transmembrane viral E5/E8 and cellular EVER proteins interact both with the zinc transporter ZnT1, and are likely to modulate zinc homeostasis. EV may thus represent a primary deficiency in intrinsic, constitutive immunity to betapapillomaviruses, or constitute a primary deficiency in innate immunity (or both). Keratinocytes, the home cells of HPVs, are likely to play a central role in both cases. An important issue is to establish which cellular genes involved in intrinsic and innate antiviral responses play a part in the outcome of infections with other HPV types, such as genital oncogenic HPVs.
Florid and widespread respiratory papillomatosis is a devastating disorder occurring in a subset of patients with recurrent respiratory papillomatosis, and it poses a major dilemma for the patient and the surgeon. Contrary to common belief, the distribution of papilloma lesions is not random, but follows a predictable pattern, with lesions occurring at anatomic sites in which ciliated and squamous epithelia are juxtaposed. The predominant sites of disease in recurrent respiratory papillomatosis are the limen vestibuli, the nasopharyngeal surface of the soft palate, the midzone of the laryngeal surface of the epiglottis, the upper and lower margins of the ventricle, the undersurface of the vocal folds, the carina, and bronchial spurs. These sites have the common histologic feature of a squamociliary junction. Papillomata also occur at the tracheostomy tract and at the midthoracic trachea in patients with tracheostomies. At the latter sites, abrasion injury to ciliated epithelium heals with metaplastic squamous epithelium and creates an iatrogenic squamociliary junction. The apparent preferential localization of papilloma at squamociliary junctions has at least 2 implications: first, that detection of occult asymptomatic papillomata is enhanced by careful examination of squamociliary junctions, and, second, that iatrogenic papilloma “implantation” is preventable by avoiding injury to nondiseased squamous and ciliated epithelia.
Fourteen Algerian patients with epidermodysplasia verruciformis were studied. Five patients (35%) were children of consanguineous marriages and 4 (28%) had affected siblings. The clinical features were classic with an association, in all patients, of pityriasis versicolor-like macules and flat wart-like papules. Bowenoid cancers and squamous-cell carcinomas occurred in 6 (42%) patients. The interval between warts and cancers was approximately 17 years. The cancers were located on sun exposed skin, especially the forehead. Electron microscopy showed, in some cells, viral particles in paracrystallin arrays. No virus particles were found in the cancers. Virologic studies using restriction endonuclease analysis and DNA blot hybridization have shown benign lesions to be associated with 10 HPV types (HPV-3,5,8,10,15,19,20,28 and HPV-X1 and HPV-X2 not yet repertoried). Characterization of HPV-DNA in 3 cancers showed genome copies of HPV-5 in a basal-cell carcinoma. More than 65% of our patients have depressed cellular mediated immunity by using TTL to 3 mitogens, E-rosette and DNCB tests. Treatment with etretinate (Tigason) resulted in partial temporary improvement of the benign lesions and in reduction of 2 small bowenoid cancers.
The Bethesda System for reporting the results of cervical cytology was introduced in 1988 and revised in 1991 using the actual laboratory and clinical experience with the system. After 10 years of widespread use and advances in biologic understanding of cervical neoplasia, it was felt important to reexamine this terminology. After extensive internet web-based discussion groups on various aspects of the System, a workshop was held at the National Cancer Institute in Bethesda, Maryland, with participation from a broad range of constituents including cytologists, pathologist, clinicians, epidemiologists, patient advocates, and attorneys. This consensus statement is the report of this workshop. The following table (Table 1) is an abstract of the consensus statement.
Epidermodysplasia verruciformis (EV) is a rare lifelong skin disease, which begins during infancy or childhood. It is induced by numerous specific types of human papillomaviruses (HPVs), sometimes including the HPVs associated with flat warts in the general population. EV is characterized by refractory, disseminated skin lesions resembling flat warts, or presenting as macules of various colors. Cutaneous carcinomas in situ or invasive carcinomas usually of Bowen’s type, appear in a high proportion of the patients, generally at an early age. HPV DNA sequences, usually HPV type 5, are regularly detected in EV carcinomas. EV is a multifactorial disease which involves genetic, immunological, and extrinsic factors, in addition to specific HPVs. This has been suggested by the parental consanguinity and the sibling involvement observed in some cases, the impaired cell-mediated immunity reported in most patients, and the usual localization of skin cancers in light-exposed areas. Reviews on EV have been published by Maschkilleisson (1931), Sullivan and Ellis (1939), Midana (1949), Jablonska and Milewski (1957), Bilancia (1961), Jablonska et al. (1966, 1972), Oehlschlaegel et al. (1966), Relias et al. (1967), Tsoitis et al. (1973), Rueda and Rodriguez (1976), Kaufmann et al. (1978), Lutzner (1978), Orth et al. (1980), Jablonska and Orth (1985), and Orth (1986).
We have previously detected a group of human papillomaviruses originally found in skin lesions of epidermodysplasia verruciformis (EV) patients in skin cancers from renal transplant recipients and from non-immunosuppressed patients. The reservoir of EV-HPVs is still unknown. In the current study we investigated whether EV-HPV DNA can be detected in plucked hairs from renal transplant recipients and healthy volunteers. Hairs were plucked from eyebrows, scalp, arms, and/or legs and DNA was subsequently isolated. To detect EV-HPV, we used nested PCR with degenerate primers Located in the RPV LI open reading frame. HPV DNA was detected in hairs from one or more sites in all 26 renal transplant recipients tested. Forty-five of 49 samples (92%) from these 26 patients were positive. The HPV type was successfully determined by sequencing in 38 samples, and all types belonged to the EV-HPVs. In ten of 22 healthy volunteers (45%), EV-HPV DNA was also detected in hairs from one or more sites. Twenty of 38 samples (53%) were positive, of which 17 samples were typed as EV-HPV types. These findings indicate that EV-HPV is subclinically present in the skin of the general population. Immunosuppression may lead to activation of the virus, explaining the finding that the apparent prevalence of EV-HPV in plucked hairs from renal transplant patients is higher than in those from the volunteers. If a dose-response situation exists for the carcinogenic potential of HPV infection, this finding may be relevant to the increased risk of skin cancer in this group of patients.Keywords: HPV, nested-PCR, immuno suppression
Infection with human papillomavirus (HPV) is almost universal and eventually asymptomatic, but pathologic infection with HPV is severe, recurrent, and recalcitrant to therapy. It is also an underappreciated manifestation of primary immunodeficiency. Mutations in EVER1, EVER2, GATA2, CXCR4, and dedicator of cytokinesis 8 (DOCK8) are typically associated with extensive HPV infections, whereas several other primary immune defects result in severe HPV much less frequently. We review immunodeficiencies with severe HPV infections and the mechanisms underlying them.
Objectives:
Human papillomavirus (HPV), one of the commonest sexually transmitted infections, may be a cofactor in HIV acquisition. We systematically reviewed the evidence for an association of HPV infection with HIV acquisition in women, heterosexual men and men who have sex with men (MSM).
Design:
: Systematic review and meta-analysis.
Methods:
Studies meeting inclusion criteria in Pubmed, Embase and conference abstracts up to 29 July 2011 were identified. Random effects meta-analyses were performed to calculate summary hazard ratios (HR). Publication bias and statistical heterogeneity were evaluated and population attributable fractions (PAFs) calculated.
Results:
Eight articles were included, with previously unpublished data from five authors. Seven studies found an association between prevalent HPV and HIV acquisition. Risk of HIV acquisition in women doubled with prevalent HPV infection with any genotype [HR = 2.06 (95% CI = 1.44-2.94), I = 0%], although adjustment for confounders was often inadequate. The effect was similar for high-risk [HR = 1.99 (95% CI = 1.54-2.56), I = 8.4%] and low-risk [HR = 2.01 (95% CI = 1.27-3.20), I = 0%] HPV genotypes with weak evidence of publication bias (P = 0.06). Two studies in men were identified: both showed an association between HPV infection and HIV acquisition. Unpublished data from one of two studies in women indicated an association between genotypes targeted by HPV vaccines and HIV acquisition. PAFs for HIV attributable to infection with any HPV genotype ranged between 21 and 37%.
Conclusion:
If further studies validate the association between HPV infection and HIV acquisition, HPV vaccines may reduce HIV incidence in high HPV prevalence populations, in addition to preventing cervical cancer. HIV surveillance studies during implementation of HPV vaccine programmes are warranted.
Papillomaviruses are highly tissue-specific, and are characterized by a specific mode of interaction with the squamous epithelia they infect.1 It has been proposed that this interaction presents two successive steps that depend on the stage of differentiation of the host cell in the wart. In the basal germinal cells the viral replication is never observed. Based on the well-studied model of the papillomas induced by the Shope cottontail rabbit papillomavirus, it is most likely that the viral genome is present in the basal cells as a small number (10 to 50) of extrachromosomal copies.2,3 The viral messenger RNAs expressed correspond to nonstructural viral proteins, as yet unidentified, but most probably involved in the altered response of basal cells to the mechanisms regulating their mitotic rate and the size of the germinal cell population, thus resulting in the formation of a papilloma.4 Vegetative viral DNA replication is triggered upon the onset of the terminal differentiation process in the suprabasal layers, followed by the synthesis of viral structural proteins and the assembly of viral particles in more superficial layers.1,4
OBJECTIVE: To assess the relative risk of perinatal mortality, severe preterm delivery, and low birth weight associated with previous treatment for precursors of cervical cancer. DATA SOURCES: Medline and Embase citation tracking from January 1960 to December 2007. Selection criteria Eligible studies had data on severe pregnancy outcomes for women with and without previous treatment for cervical intraepithelial neoplasia. Considered outcomes were perinatal mortality, severe preterm delivery (<32/34 weeks), extreme preterm delivery (<28/30 weeks), and low birth weight (<2000 g, <1500 g, and <1000 g). Excisional and ablative treatment procedures were distinguished. RESULTS: One prospective cohort and 19 retrospective studies were retrieved. Cold knife conisation was associated with a significantly increased risk of perinatal mortality (relative risk 2.87, 95% confidence interval 1.42 to 5.81) and a significantly higher risk of severe preterm delivery (2.78, 1.72 to 4.51), extreme preterm delivery (5.33,
Epidermodysplasia verrucif ormis (EV) is a rare, lifelong disease induced by a diversity of specific human papillomaviruses (HPVs) including, in some instances, the HPVs which induce plane warts in the general population.1–4 EV provides a model of cutaneous viral oncogenesis, in which virus and host factors are important determinants.The disease starts usually in early childhood. The lesions, as a rule, do not appear at birth, even in familial cases, in spite of the heavy viral infection of the mother. The reason for this latency period is not known.
Human papillomaviruses (HPVs) are small DNA viruses of the papovavirus family, with more than 100 types already described. Their importance in human disease cannot be overemphasized because these agents are among the most common pathogens in cutaneous infectious diseases and are very important in a subset of predominantly, but not exclusively, genital squamous-cell carcinomas. HPVs can be associated with a variety of cutaneous as well as mucosal manifestations. Some types of HPVs are associated with increased risk of epithelial malignancies; these have been divided into low-risk and high-risk types based on their oncogenic potential. Clinical and histological features of HPV infection vary according to individual susceptibility (e.g., immunosuppressed patients), site of involvement, and type of HPV implicated. The histological features of HPV infection are very easy to identify on sections stained with hematoxylin and eosin. However, many findings usually associated with HPV infection are entirely non-specific. Additional current diagnostic methods for identification of HPV in tissues include techniques based on the detection of viral DNA; namely, in-situ hybridization and polymerase chain reaction (PCR). This article reviews the main clinical and histopathological cutaneous manifestations of HPV infection, including common warts, plantar warts, plane warts, condyloma acuminatum, Bowenoid papulosis, and epidermodysplasia verruciformis. Emphasis is placed on the clinical and histological features of these various manifestations, including a brief discussion about the routinely used laboratory methods for detecting HPV in tissues.
Strong evidence now supports the adoption of cervical cancer prevention strategies that explicitly focus on persistent infection with the causal agent, human papillomavirus (HPV). To inform an evidence-based transition to a new public health approach for cervical cancer screening, we summarize the natural history and cervical carcinogenicity of HPV and discuss the promise and uncertainties of currently available screening methods. New HPV infections acquired at any age are virtually always benign, but persistent infections with one of approximately 12 carcinogenic HPV types explain virtually all cases of cervical cancer. In the absence of an overtly persistent HPV infection, the risk of cervical cancer is extremely low. Thus, HPV test results predict the risk of cervical cancer and its precursors (cervical intraepithelial neoplasia grade 3) better and longer than cytological or colposcopic abnormalities, which are signs of HPV infection. The logical and inevitable move to HPV-based cervical cancer prevention strategies will require longer screening intervals that will disrupt current gynecologic and cytology laboratory practices built on frequent screening. A major challenge will be implementing programs that do not overtreat HPV-positive women who do not have obvious long-term persistence of HPV or treatable lesions at the time of initial evaluation. The greatest potential for reduction in cervical cancer rates from HPV screening is in low-resource regions that can implement infrequent rounds of low-cost HPV testing and treatment.
The genus betapapillomavirus (betaPV) presently comprises more than 40 virus types including the so-called epidermodysplasia verruciformis (EV)-associated HPV, which were originally detected in EV-patients by Southern blot hybridization. BetaPV are ubiquitous in the general population and frequently establish themselves already during the first weeks of life. Hair follicles are regarded as natural reservoir. About 25% of betaPV detected in adults persist for at least 9 months. Due to very low virus production, seroconversion against betaPV starts sluggishly. Hyperproliferation of keratinocytes in psoriasis patients or after severe burns stimulates virus replication. Massive virus replication only occurs in EV-patients, associated with the induction of disseminated skin lesions with a high risk of malignant conversion. In 75% of EV-patients this can be put down to homozygous, inactivating mutations in the genes EVER1 or EVER2. A transgenic mouse model substantiated the crucial role of increased HPV8 oncogene expression, induced by UV-irradiation or wounding, for tumor induction.
Human papillomavirus (HPV) is the most common sexually transmitted infection. The effect of HPV on public health is especially related to the burden of anogenital cancers, most notably cervical cancer. Determinants of exposure to HPV are similar to those for most sexually transmitted infections, but determinants of susceptibility and infectivity are much less well established. Gaps exist in understanding of interactions between HPV, HIV, and other sexually transmitted infections. The roles of mucosal immunology, human microbiota at mucosal surfaces, host genetic factors and hormonal concentrations on HPV susceptibility and infectivity are poorly understood, as are the level of effectiveness of some primary or secondary preventive measures other than HPV vaccination (such as condoms, male circumcision, and combination antiretroviral therapy for HIV). Prospective couples studies, studies focusing on mucosal immunology, and in-vitro raft culture studies mimicking HPV infection might increase understanding of the dynamics of HPV transmission.
Larson DA, Derkay CS. Epidemiology of recurrent respiratory papillomatosis. APMIS 2010; 118: 450–454.
Recurrent respiratory papillomatosis (RRP) was first described in the 1800s, but it was not until the 1980s when it was convincingly attributed to human papilloma virus (HPV). RRP is categorized into juvenile onset and adult onset depending on presentation before or after the age of 12 years, respectively. The prevalence of this disease is likely variable depending on the age of presentation, country and socioeconomic status of the population being studied, but is generally accepted to be between 1 and 4 per 100 000. Despite the low prevalence, the economic burden of RRP is high given the multiple procedures required by patients. Multiple studies have shown that the most likely route of transmission of HPV in RRP is from mother to child during labor. Exceptions to this may include patients with congenital RRP who have been exposed in utero and adult patients who may have been exposed during sexual contact. Although cesarean section may prevent the exposure of children to the HPV virus during childbirth, its effectiveness in preventing RRP is debatable and the procedure itself carries an increased risk of complications. The quadrivalent HPV vaccine holds the most promise for the prevention of RRP by eliminating the maternal reservoir for HPV.
Pooled data on human papillomavirus (HPV) type distribution in invasive cervical cancer (ICC) can help to predict the potential impact of HPV type-specific vaccines and screening tests, and to understand the carcinogenicity of HPV types. We performed a meta-analysis of HPV type-specific prevalence data published from 1990 to 2010, including a total of 243 studies and 30,848 ICC. The proportion of ICC associated with HPV16 and/or 18 (HPV16/18) was between 70 and 76% in all world regions except Asia. In Western/Central Asia, 82% of ICC was HPV16/18-associated compared to only 68% in Eastern Asia. The 12 most common HPV types identified, in order of decreasing prevalence, were HPV16 (57%), 18 (16%), 58, 33, 45, 31, 52, 35, 59, 39, 51 and 56. The prevalence of other types, phylogenetically related to those above, ranged from <0.1% for HPV85 to 0.6% for HPV68. Overall HPV prevalence increased significantly from 85.9% in studies published from 1990 to 1999 to 92.9% in studies published from 2006 to 2010. Prevalence increases were large for multiple infections (from 4.0 to 15.7%) and for HPV16 (from 51.8 to 60.0%, including HPV16 alone or in multiple infections). Smaller but significant increases in prevalence were also seen for HPV39, 53 and 58. A large amount of recently published data has improved the understanding of the contribution of a broad range of HPV types to ICC in different world regions. However, estimating the fraction of ICC attributable to different types is increasingly complicated by the detection of multiple HPV infections in ICC.
Incidence is increasing rapidly, with implications for prognosis and policy
We report the case of a patient with a large Buschke-Lowenstein tumour which had previously recurred following local excision. A preferred treatment modality for this rare variant of human papillomavirus has not been clearly defined. Treatment with chemo-radiotherapy in this case resulted in complete resolution of the disease without the need for further surgical intervention.
The relationship between cervical cancer and human papillomavirus (HPV) is well known. Like cervical cancer, anal cancer is preceded by a series of precancerous changes, raising the possibility that like cervical cancer, anal cancer can be prevented. Further, given the known risk factors for anal cancer, prevention efforts could be targeted to high-risk groups, providing a unique example of a screening program targeted to high-risk individuals. This article describes the epidemiology of anal HPV infection, anal intraepithelial neoplasia, and anal cancer among men and women, as well as current efforts to prevent anal cancers.
Genital human papillomavirus-related lesions occurring in 74 patients and cellular swab samples taken from their underwear were analyzed with a filter hybridization technique (ViraPap-ViraType, Life Technologies Inc., Gaithersburg, Md.) for human papillomavirus deoxyribonucleic acid. Human papillomavirus deoxyribonucleic acid was found in 54 of 74 (72%) lesional tissues and 13 of 74 (17%) swabs from the underwear. Recurrence rates in patients with and without positive underwear swabs were 61% and 29% (p less than 0.05), respectively.
• Alpha interferon did not prevent the persistence or expression of human papillomavirus (HPV) types 6 or 11 in respiratory tract papillomas. Seventeen patients receiving interferon therapy for a minimum of six months and a maximum of 39 months still had one to ten copies per cell genome of HPV DNA in their laryngeal tissues, seen by Southern blot hybridization. In papillomas that recurred during treatment, HPV RNA could be detected by in situ hybridization, and capsid protein could be detected by immunoperoxidase staining. Persistence of the HPV DNA, and recurrences that occurred during therapy, are attributed to the failure of interferon therapy to eliminate latent virus.
(Arch Otolaryngol Head Neck Surg 1988;114:27-32)
Human-papillomavirus (HPV)-induced cutaneous lesions differ considerably in their clinical morphology. This was thought to depend mainly on anatomic location and other factors related to the host and to the age of the lesions. It was long-assumed that a single virus was responsible for all of these lesions.1Disclosure of the plurality of HPV types associated with skin warts2–9 raised the problem of the relation of clinical morphology to the distinct types of HPV. This was first suggested by the characterization of distinct HPVs from different types of lesions: HPV1 from deep plantar warts,3 HPV2 from common hand warts,3 and HPV3 from plane warts and flat wart-like lesions of patients with epidermodysplasia verruciformis (EV).5 At present, 39 types of HPVs are recognized, with several subtypes for many of them.10 Some HPV types are specifically associated with cutaneous warts: HPV1, 2, 3, 4, 7, 10, 26–28, and a great number of them are associated with EV.10,11The problem of specific or preferential association of distinct HPVs with warts differing in morphology and/or location is still controversial, since only a limited number of cases were studied,2–17 and no widely accepted clinical and histologic criteria are available for the differentiation between wart types.18–21 For instance, myrmecia warts are often not distinguished from common or mosaic warts in spite of their very precise histologic and clinical description by Lyell and Miles.22Our aim is to present the available data on the association of different types of cutaneous warts with distinct HPVs, and to find out whether it is possible to evaluate the type of infecting HPV on the basis of clinical and histologic features. Such recognition might be important because of the differences in clinical course, contagiousness, and response to treatment of lesions associated with different HPVs.
A prevalence study of 8298 pupils in compulsory school grades 7--9 was performed in the county of Västerbotten (AC county) in northern Sweden. Prevalence figures for 19 skin diagnoses are presented. A female dominance was found in the prevalence of atopic dermatitis, striae distensae and plantar warts, and a male dominance in multiple pigmented naevi. A sharp drop in atopic dermatitis was found at 13 years. Acne vulgaris showed a negative correlation with atopic dermatitis, ephelides, multiple pigmented naevi and spider naevi and a positive correlation with striae distensae. Atopic dermatitis was negatively correlated to ephelides and multiple pigmented naevi as well as acne. Pronounced variations in the occurrence of plantar warts were registered between different schools. Of the 19 diagnoses registered, only hereditary palmo-plantar keratodermia has a geographical distribution compatible with an increased prevalence of the disease in the AC county. Consequently the figures presented for the other diagnoses are considered to be representative for a north European Caucasian population.
Nineteen patients with carcinoma cuniculatum are presented. Of these, 17 were male and two were female. The age range was from 26 to 73 years with a mean of approximately 54 years. Sixteen tumours were located on the foot, the other three were situated on the knee, wrist and finger respectively. The pathological features of carcinoma cuniculatum are described and the aetiology of the tumour is discussed.
Ultrastructural changes in Langerhans cells during spontaneous involution of plane warts were examined. In areas with activated macrophages and epidermal cell interaction, Langerhans cells showed signs of enhanced cellular activity with an increased number of Langerhans cell granules, as in contact dermatitis. The fine structure of Langerhans cell granules, however, was unusual in that the vesicular portion was surrounded by a membrane, and this portion frequently occurred independently taking the shape of a loop.
A recent study comparing heterosexual men with and without confirmed sexually transmitted diseases (STDs) in an urban STD clinic showed that uncircumcised men were less likely than circumcised men to have genital warts detectable by clinical examination (adjusted odds ratio 0.7, 95% confidence interval 0.4, 0.9). Based on these initial findings we hypothesised that the appearance and anatomic distribution of genital warts, and possibly treatment response, may be different for circumcised and uncircumcised men.
The anatomic location, appearance, number of warts, and response to treatment was investigated through review of medical records of 459 heterosexual men with genital warts detected in 1988.
Age- and race-adjusted estimates indicated that among men with genital warts, warts were detected much more commonly on the distal penis--that is, the corona, frenulum, glans or urethral meatus-, among uncircumcised men (26%) than among circumcised men (3%) (OR 10.0, 95% CI 3.9, 25.7). Where the appearance was specified, warts were more often described as condylomatous in uncircumcised men and slightly more often as papular in circumcised men. No significant difference between circumcised and uncircumcised men was seen in the number of return visits to the clinic for persistent warts after treatment with liquid nitrogen: 2.2 visits for 19 uncircumcised men and 2.3 visits for 149 circumcised men.
Circumcised men were more likely than uncircumcised men to have genital warts, but when present, warts were more often located on the distal portion of the penis among uncircumcised men. This paradox is not understood, but could reflect either nonspecific resistance to proximal penile warts conferred by the foreskin, or heightened susceptibility to various HPV types in uncircumcised men, some of which may confer subsequent immunity to genital warts.
This study set out to determine tbe prevalence and predictors of warts in Britisb schoolchildren by analysing medical examination data from a national birth cohort study of 9263 Britisb children born 3–9 Marcb 1958.
The prevalence of visible warts, according to a medical officer, at the age of 11 was 3.9% (95% confidence intervals 3.5–4.3) and 4.9% (95% confidence intervals 4.5–5.4) at 16. Of the 364 children noted to have warts at the age of 11, 337 (93%) no longer had warts at 16. Residence in tbe soutb of Britain, having a father with a non-manual occupation, being an only child, and belonging to an ethnic group other than white European were all associated with a decreased risk of visible warts. Region of residence was the strongest predictor of wart prevalence. There were no sex differences in wart prevalence. Warts represent a common source of morbidity in Britisb scboolcbildren. Euture studies sbould take into account age, regional factors, social class, family size and etbnic group wben comparing wart sufferers with other subjects.