Manifestations Of Human Papillomavirus Infection Research Articles

Digital analysis of colposcopic images with acetowhite epithelium in "real-time" mode

Digital analysis is a method of assessing qualitative data by converting them into quantitative data using a personal computer’s graphics processing unit (GPU). Visual changes on the cervical surface in human papillomavirus (HPV)-associated pathology can be evaluated by extended colposcopy with a 3–5% acetic acid test and Schiller’s test. Acetowhite epithelium (appears after a test with acetic acid) in the form of flat condyloma is one of the main clinical manifestations of HPV infection (excluding manifestations on the metaplastic epithelium). The intensity of acetowhite epithelium (AWE) is a subjective parameter during gynecological examination, and to exclude the malignant process, a histology or liquid-based cytology should be performed. Objective assessment of the AWE intensity is introduced by digital image analysis using specialized software. The aim. To improve the assessment of visual changes of acetowhite epithelium on the cervical surface using a digital approach as an additional tool when performing extended colposcopy. Materials and methods. Colposcopy images of 359 patients were estimated by digital approach. Colposcopy images were made with a screenshot function after performing extended colposcopy. Screenshots of the cervix were converted to 8-bit type. This allowed us to estimate the intensity of AWE by software ImageJ. Index grey value (IndGV) was calculated to estimate the intensity of AWE. The IndGV data were assessed by MS office 365 (Excel v16.46) and RStudio v1.2.5042 statistical packages. Results and conclusion. The quantification approach detects the severity of AWE on the cervical surface. IndGV correlates with the grades of cervical intraepithelial neoplasia (CIN) and clinical manifestations of HPV. The clinical manifestations of HPV infection in CIN have a direct dependence on digital measurement as grey value (GV). These indicators give the opportunity to evaluate clinical manifestations in digital analysis in real-time mode, which does not require a significant financial investment. IndGV can be used as a prognostic factor of the severity of HPV infection and its clinical forms (CIN I–III and cervical cancer). Key words: digital medicine, quantitative approach, acetowhite epithelium, HPV infection

Recurrent Subungual Viral Warts

Warts, cutaneous manifestations of human papillomavirus infection, are difficult to cure. Warts have a high recurrence rate and there is no known single completely effective treatment. In this case, a 14-year-old boy presented with a subungual wart of the thumb that did not respond to salicylic acid. Excision was performed due to discomfort caused by pain and deformation of the nail plate. After the first operation, the patient had to receive two revision operations due to recurrence. Epithelialization was completed 2 weeks after the second revision surgery, after which there was no recurrence. According to literature review, many immunocompetent patients can expect spontaneous recovery without any treatment. If treatment is necessary, salicylic acid and cryotherapy have the strongest evidence of efficacy and are recommended as first-line treatments. Various other treatments are used alone or in combination. During surgical removal, special attention should be given for complete removal of the wart to prevent recurrence.

Clinical and epidemiological features of papillomavirus infection manifestations on the example of cervical cancer and genital warts

Background: Cervical cancer and genital warts (GWs) are some of the most common manifestations of human papillomavirus infection (HPV). These lesions cause significant damage to the reproductive health of the population, which leads to increased attention to the prevention of HPV infection among various population groups.
 Aims: To determine the clinical and epidemiological features of the HPV manifestations by the example of cervical cancer and genital warts.
 Methods: A retrospective analysis of anamnestic information of 115 women with an established diagnosis of cervical cancer and 177 patients with an established diagnosis of GWs was performed. The clinical and epidemiological characteristics of patients with diagnoses of GWs and cervical cancer were based on the development of outpatient admission cards and inpatient histories, as well as test data for HPV.
 Results: HPV 16 was the most common HPV type among patients with GWs and cervical cancer ― it was detected in 37.6% of cases. Also the most frequently encountered: HPV 6/18/11/31/51/52. In 43.2% cases of HPV detection, two or more types were detected at once, the most common combinations: HPV16 and HPV18, HPV6 and HPV16, HPV6 and HPV11. Analysis of the frequency of screening for cervical cancer and visits to the gynecologist for 5 years before establishing the diagnosis showed that among those who did not screen for cervical cancer, the risk of diagnosing stage IIIV was 5.2 times higher than among individuals who underwent cervical screening 2 years ago, or once a year for the last five years. Among patients with GWs who had 2 or more sexual partners for 1 year, 13.5% of patients regularly used barrier contraception methods (condoms) during sexual contact, not regularly ― 61.5%, did not use them at all ― 25.0%.
 Conclusions: Identifying the clinical and epidemiological features of HPV infection should contribute to the development of new and optimize existing prevention programs for a wide range of HPV-associated diseases.

Features of clinical manifestations and therapy of human papillomavirus-associated diseases of anogenital localization

Relevance. The article deals with one of the most common manifestations of human papillomavirus infection - condylomata acuminata/anogenital warts. Aim. To provide current information on human papillomavirus (HPV), its transmission pathways, epidemiology and pathogenesis of HPV-associated diseases of anogenital localization; to describe in detail clinical forms of anogenital warts; to discuss modern methods of anogenital warts treatment, including destructive (physical, chemical), surgical, immunological and combined ones; to show evidence of effectiveness for the use of inosine pranobex, an immunomodulator with antiviral activity, at genital warts of different localization; to present foreign and domestic studies data. Materials and methods. To write this review a search for domestic and foreign publications in Russian and international search systems (PubMed, eLibrary, etc.) for the last 2-15 years was conducted. The review includes articles from peer-reviewed literature. Conclusion. The use of inosine pranobex in combination with destructive methods for a treatment of HPV-associated diseases contributes to more active resolution of the pathological process, reduces a rate of relapses and prevents carcinogenesis due to effective elimination of HPV from lesions. The drug has a good tolerability, minimal side effects, could be used in individual dose and in combinations with other treatment methods that allows to use inosine pranobex for HPV treatment in a wide range of patients.

Cutaneous manifestations of human papillomavirus infection

Cutaneous manifestations of human papillomavirus infection

Prevalence Study of Injuries Caused by HumanPapillomavirus (HPV) in the Cascavel Population

To determine the prevalence of human Papillomavirus (HPV)infection in the population of Cascavel, Parana, Brazil, correlating the risk factors with the infection and seeking to identify the general situation of the disease in the city. Records of patients from the Specialized Center for Infectious-Parasitic Diseases (CEDIP, Cascavel) were analyzed between 2010-2014 and clinical files of patients affected by some manifestation of HPV infection were included. Data on age, gender, sexual orientation, number of sexual partners in 12 months, history of another Sexually Transmitted Disease (STD) or presence of STD associated with clinical manifestation of HPV infection, schooling, smoking, contraceptive use and condom use. Of 2,889 records, HPV infection affected 1,189 patients (41%). The incidence of HPV infection in Cascavel is approximately 237 new cases per year, with the most common clinical manifestation of genital warts (84%). The profile of patients most affected by the manifestations of HPV was of both genders, young (42%), at the onset of sexual activity (46%), heterosexual (91%), irregular use of condoms (69%) and use of oral contraceptives (45%). HPV infection has a high prevalence in Cascavel and requires further public health measures to control the disease.

Ассоциации уровня интерферона и клинических признаков различных типов вируса папилломы человека

Objective: to determine the compliance of the serum interferon level (IFN) with the clinical signs of the female reproductive system diseases in the presence of various types of human papillomavirus (HPV). Materials and methods. In total 250 women aged 23–37 years were divided into two groups. The main group I comprised patients with clinical manifestations of human papillomavirus infection (PVI). The control group was divided into two subgroups: group IIA included women who had HPV-positive PCR without clinical signs of PVI, in group IIB were enrolled clinically healthy women with HPV-negative PCR results. Digene HPV 6,11,16,18,26,31,33,35,39,44,45,51,52,53,56,58,59,68,69,73,82 test with viral load was performed; as well as examination for bacteria, chlamydia, myco- and ureaplasma. The IFN level in blood serum was detected in all patients. Results. In group I, the identified HPV types were responsible for the dysplastic processes of the genital organs. Viral load less than 3 Lg was observed in 28 (56.0%) patients of group I and 18 (36.0%) of group IIA, from 3 Lg to 5 Lg – in 67 (44.6%) patients of group I and 4 (8.0%) of group IIA. In group I, the level of 2–4 Lg was associated with high-grade dysplastic changes in the genital organs and skin of the perineal area, which require electrosurgical treatment. In the control subgroup with a higher level of serum interferon, clinical manifestations of PVI were not diagnosed. Conclusions. The HPV types 6, 11, 16, 18, 26, 31, 33, 35, 39, 44, 45, 51, 52, 53, 56, 58, 59, 68, 69, 73, 82 are associated with dysplastic diseases of the cervix, vagina, external genitalia; the prognosis of the disease and severity of dysplastic processes is connected with the viral load of 3 Lg to 5 Lg, as well as the IFN serum level. These tests may be recommended to predict the disease development and use in the comprehensive pregravid preparation.

Human papilomavirus infection in couples. A discussion

In the Russian literature, insufficient attention is given to the study of the flow of human papillomavirus infection in couples. The aim of the study was to establish the frequency of infection with oncogenic HPV types and clinical manifestations of human papillomavirus infection in regular sexual partners. Surveyed 38 couples who are regular sexual partners in the past three years and denying unauthorized sex. PVI revealed at 70.9 per cent of women who had contact with an infected partner and 79.8 per cent of men. The average age for first sexual intercourse in women was 18.2 years, men - 16.7 years. 80% of men before marriage had more than 5 sexual partners. In 37 of 38 pairs of HPV types of high oncogenic risk coincide. The most frequently detected HPV type 16, are a few less - HPV 51, 31 and 39. Clinical manifestation of HPV infection among sexual partners of the 38 couples not identified, subclinical form of infection in women and men after colposcopy and peniscopy were found with equal frequency (18.4%) and (15,8%), respectively. The descriptions of peniscopy in men with HPV of high oncogenic risk was done.

Оценка эффективности и безопасности применения имихимода в лечении субклинических и клинических проявлений персистирующей папилломавирусной инфекции шейки матки у пациенток раннего репродуктивного возраста

Objectives. HPV infection is a major risk factor for cervix cancer. This study evaluated cervical application of imiquimodfortreatment of subclinical (flat condyloma) and clinical (CIN I, LSIL) manifestations of human papillomavirus infection. Methods. An open controlled study (n=28) efficacy and safety of imiquimod (5% cream Aldara) in 1-2 months. Results. All patients treated had complete clinical responses. Clinical efficacy of treatment at 1 month was 96,4%, in 2 months - 100%. Microbiological efficacy (full HPV-clearance) achieved in 60,7% of cases, in other cases there was a decrease in viral load. Elimination of the 16 types of virus was achieved in 80% of cases. Immunocytochemical study showed higher levels of expression of Toll-like receptor 4 and 9 type in the endo - and ectocervix after treatment. Undesirable effects were not grounds for termination of treatment.Conclusions. The trial does support the feasibility and acceptability of the use of imiquimod on the cervix in treatment of manifestations of human papillomavirus infection.

Warty dyskeratoma—“follicular dyskeratoma”: Analysis of clinicopathologic features of a distinctive follicular adnexal neoplasm

Background: The clinicopathologic spectrum of warty dyskeratoma (WD) is not well characterized and the pathogenesis of this unusual lesion is still unclear. Objective: We reviewed the clinical and histopathologic spectrum of WD and investigated a possible involvement of human papillomavirus (HPV) infection in onset of this lesion. Methods: A total of 46 cases of WD were analyzed clinically and histopathologically. Polymerase chain reaction (PCR) analysis for HPV-DNA was performed in 13 lesions of WD. Results: A total of 46 lesions of WD from 45 patients (M/F ratio, 1:1.8; mean age 59.8 years, median 61 years, age range 3-88 years) presented as solitary papules or small nodules on the head and neck (32 cases), trunk (9 cases), lower extremities (4 cases), and upper extremities (1 case). One patient had 2 lesions. No patient had clinical signs of Darier's or Grover's disease. Histopathologically on scanning magnification, lesions showed mainly 3 architectural patterns, namely, cup-shaped (29 cases), cystic (6 cases), and nodular (2 cases). In 9 cases, a combination of two of these morphologic patterns was observed. Characteristically, the epithelial component in all WDs displayed foci of acantholytic dyskeratosis. Variable features suggestive of follicular differentiation toward the infundibular portion of a normal hair follicle were also observed, including a focal contiguity to pilosebaceous units in most cases (63%), and the presence of small infundibular cystic structures in a subset of lesions (46%). The majority of lesions (83%) also revealed a hyalinized or fibrous stroma with intrastromal clefts. PCR analysis for HPV-DNA performed in 13 cases inclusive of all representative architectural patterns was negative. Conclusion: We conclude that WD shows a wider spectrum of morphologic features than previously recognized. Despite some histopathologic similarities to viral warts, WD is not a manifestation of HPV infection. On the other hand, the majority of these lesions display overall histopathologic features consistent with a follicular adnexal neoplasm. On the basis of this finding, we propose the alternative term follicular dyskeratoma to better reflect the distinctive features of this peculiar lesion. (J Am Acad Dermatol 2002;47:423-8.)

Cellular manifestations of human papillomavirus infection in laryngeal tissues

Cellular manifestations of human papillomavirus infection in laryngeal tissues

Cellular manifestations of human papillomavirus infection in laryngeal tissues.

Although epidemiologic studies have suggested human papillomavirus (HPV) to be an etiological agent in laryngeal carcinogenesis, little is known on the cellular manifestations of HPV infection in these tumors. In this study, we investigated the frequency of HPV infection in various neoplastic and non-neoplastic laryngeal tissue and its association with expression of the proliferating cell nuclear antigen (PCNA) and the tumor suppressor protein p53. Tissues were analyzed by polymerase chain reaction (PCR) for the presence of HPV and by immunocytochemistry for the expression of p53 and PCNA. None of the six normal laryngeal tissues showed the presence of HPV. Thirteen out of the 16 papillomas were positive for HPV, while 15 out of the 44 invasive cancers were HPV positive. PCNA expression increased as the lesion progressed through increasing histological abnormality (r = 0.64400, P = 0.00000). The correlation between the type of laryngeal neoplasm and p53 accumulation was significant (r = 0.54839, P = 0.00000). Significant correlation was also evident between presence of HPV and p53 accumulation (r = 0.34259, P = 0.00424) and PCNA expression (r = 0.036024, P = 0.00266) indicating that HPV positive tumors showed significant p53 accumulation and increased proliferation. There was also correlation between p53 and PCNA expression (r = 0.67475, P = 0.00000) indicating that in all tumors with p53 accumulation, there was a corresponding increase in PCNA expression. The results suggests that changes in p53 and PCNA expression may be associated with HPV infection, and could play a role in laryngeal carcinogenesis.

Human papillomavirus-associated oral warts among human immunodeficiency virus-seropositive patients in the era of highly active antiretroviral therapy: an emerging infection.

Oral warts are a manifestation of human papillomavirus infection that have been noted infrequently in persons with human immunodeficiency virus (HIV). A nested case-control study was conducted to assess rates of and risk factors for oral warts among a cohort of HIV-seropositive patients. From 1997 through 1999, 56 patients with oral warts were identified among 2194 HIV-positive patients attending an urban oral health center (prevalence, 2.6%). Incident cases of oral warts were significantly more likely to have been diagnosed in 1999 than they were in 1997-1998 (P=.001). Multivariate analysis indicated that the risk of oral warts was associated with a >/=1-log(10) decrease in HIV RNA level in the 6 months before diagnosis of oral warts (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.08-5.11) and with serologic evidence of chronic or previous infection with hepatitis B virus (OR, 2.66; 95% CI, 1.31-5.41). The incidence of oral warts in HIV-seropositive patients appears to be increasing in the era of highly active antiretroviral therapy. Oral warts were associated with reductions in virus load, which suggests that this may in part be related to immune reconstitution.

Cellular manifestations of human papillomavirus infection in the oral mucosa.

Human papillomavirus infection has been suggested to play a role in the development of epithelial carcinomas, particularly those of the uterine cervix. Less information is available on the role of the virus in oral lesions. It has been proposed that the viral oncoproteins specifically complex with the products of cellular tumor suppressor gene, namely E6 with p53 and E7 with retinoblastoma gene product. Inactivation or mutation in p53 gene is also known to result in loss of control over the cell cycle and increases in tumor proliferation rates. The present study examines the role of HPV infection in relation to p53 and the extent of the tumor proliferative compartment reflected by cyclin D1 and Ki-67 expression during various phases of tumor progression in the oral epithelium. Nonisotopic in situ hybridization (NISH) was performed to detect HPV 6/11 and 16/18. Expression of p53, cyclin D1, Ki-67, and the HPV 16/18 E6 protein were detected by immunocytochemistry. There was significant correlation between the extent of histological abnormality and HPV infection. A correlation (r = 0.250, P = 0.0089) was evident between the presence of HPV 16 and occurrence of invasive cancer. Expression of the tumor suppressor p53 protein also showed significant positive correlation with histology (r = 0.475, P = 0.00004). The tumor proliferative fraction also increased with the extent of histological abnormality (r = 0.387, P = 0.0003 for cyclin D1 and r = 0.463, P = 0.0001 for Ki 67). Accumulation of p53 and increase in tumor proliferation also correlated to the presence of HPV infection (r = 0.511, P = 0.00003 for p53; r = 0.478, P = 0.00002 for cyclin D1 and r = 0.521, P = 0.00004 for Ki-67). The present study thus demonstrates the importance of HPV infection in oral tissue. Expression of the high-risk HPV 16/18 E6 protein also appears to be a critical event along with aberrant p53 expression. These results are of significance to the molecular epidemiology of oral cancer and may also be used to supplement and elaborate the diagnosis of oral lesions.

Low risk of perinatal transmission of human papillomavirus: Results from a prospective cohort study

Our purpose was to evaluate the risk of perinatal transmission of human papillomavirus. Pregnant women were evaluated at <20 weeks' and between 34 and 36 weeks' gestation for genital human papillomavirus by clinical and colposcopic examination and by polymerase chain reaction. Their 151 infants were evaluated at birth, 6 weeks, and 6, 12, 18, 24, and 36 months of age for detection of human papillomavirus deoxyribonucleic acid by polymerase chain reaction on samples from the mouth, external genitalia, and anus. Polymerase chain reaction was performed with human papillomavirus L1 consensus primers and hybridization to human papillomavirus types 6, 11, 16, 18, 31, 33, 35, 39, and 45 and to a generic probe. During pregnancy 112 (74%) of 151 women had historic, clinical, or deoxyribonucleic acid evidence of genital human papillomavirus infection. At 479 infant visits, human papillomavirus deoxyribonucleic acid was detected from only five (1.5%) of the 335 genital, four (1.2%) of the 324 anal, and none of the 372 oral or nasopharyngeal specimens. A positively reacting specimen was obtained from three (4%) of 80 infants born to women with human papillomavirus deoxyribonucleic acid detected at 34 weeks' gestation and from five (8%) of 63 born to women without human papillomavirus deoxyribonucleic acid (p = 0.47). All positive results in the infants were positive only with the generic probe and were preceded or followed by negatively reacting specimens. No clinical manifestations of human papillomavirus infection were detected in any infant. The isolated detection of unclassified human papillomavirus types from infants at only single visits may represent low-level genital or nongenital human papillomavirus or may represent contamination. Although perinatal transmission of human papillomavirus is not ruled out by these data, the upper 95% confidence interval for detection of perinatal transmission from women with any evidence of genital human papillomavirus was only 2.8%.

The protean manifestations of human papillomavirus infection. New facies of an old foe: a clinical perspective

The protean manifestations of human papillomavirus infection. New facies of an old foe: a clinical perspective

Verrucous Cyst

• Human papillomavirus has been detected in a variety of cutaneous premalignant and malignant conditions, as well as in benign cutaneous warts. Changes consistent with epidermis papillomavirus infection occurring in epidermal cysts have recently been reported in the dermatologic literature only in plantar epidermal cysts. We report five examples of a form of cutaneous cyst that is histologically distinctive and that has not been previously reported, to our knowledge. We describe five cases of epidermal cysts showing marked verrucous changes of their stratified squamous inner linings, some of which also show proliferative changes. Human papillomavirus genomes were detected via polymerase chain reaction. None of the DNA probes for Southern blot hybridization demonstrated homology with the human papillomavirus types usually associated with cutaneous warts or carcinoma. We believe this cyst to represent a newly described manifestation of human papillomavirus infection, and propose the name verrucous cyst for this entity. Further studies may reveal the specific human papillomavirus type(s) associated with the verrucous cyst.

Manifestations of anogenital HPV infection in the male partners of women with anogenital warts and/or abnormal cervical smears.

The prevalence and manifestations of anogenital human papillomavirus (HPV) infection in 154 men, all of whom were the sexual partners of women with either overt anogenital warts or cervical HPV-related abnormalities, were assessed using clinical, histopathological and molecular criteria. Detailed examination of the anogenital region using a colposcope was supplemented by the use of 5% acetic acid to detect possible foci of subclinical HPV infection. Biopsies of warts and aceto-white lesions were examined histopathologically and by HPV DNA hybridization using radiolabelled HPV 6/11 and 16/18 DNA probes. More than two-thirds of the men had clinical indications of genital HPV infection: 37% had apparent macroscopic warts, almost invariably in combination with aceto-white lesions; while 34% had aceto-white lesions only. The overwhelming majority of these lesions (92%) were located on the penis only. However, only 49% of the macroscopic and 29% of the aceto-white lesions showed histological features consistent with a conclusive diagnosis of HPV infection; while the corresponding figures for HPV DNA positivity were 72% and 56% respectively. Current HPV infection was strongly associated with a past history of anogenital warts, but there was little or no correlation between the manifestations of HPV infection in the male and female sexual partners.

Clinical Manifestations of Human Papillomavirus Infection in Nongenital Sites

Our knowledge of warts dates thousands of years. Most warts represent no more than a transient infection in the hands and feet of children and adults. With the relatively recent medical advances permitting the prolonged survival of immunocompromised hosts, however, HPV-induced lesions have become an important problem. In these patients, lesions represent a recurring, intractable infection that predisposes the patient to the development of skin cancer. Such problems have been appreciated for some time in patients with EV. Newer laboratory techniques have led to an increasing number of clinical entities linked with an HPV cause in the nonimmunosuppressed host. Although evidence incriminating HPV as a causative factor for genital cancers of the cervix and the skin continues to mount, such evidence for nongenital Bowen's disease, certain squamous cell carcinomas of the skin, keratoacanthomas, and other tumors of the skin also has begun to grow. It is to be hoped that continued advances in molecular biologic techniques will further delineate the relationship between HPV and these conditions, lead to an HPV classification scheme that is more utilitarian from a clinical point of view, and ultimately lead to improved treatment.

Cytologic and histologic manifestations of human papillomavirus infection of the female genital tract and their clinical significance.

The historical developments in the recognition of the role of human papillomavirus (HPV) infection in cells and tissues of the female genital tract are briefly summarized. The identification of a specific marker cell, the koilocyte, has led to initial studies of frequency and biologic significance of neoplastic lesions of the uterine cervix associated with HPV. By molecular virology techniques, over 40 types of HPV have been identified and their tissue affinity determined. Types 6, 11, 16, 18, and 31 are most commonly associated with anogenital lesions, among them a broad spectrum of cervical intraepithelial neoplasia (CIN). While current evidence suggests that lesions associated with HPV Types 6 and 11 are potentially less harmful to the patient than lesions associated with HPV Types 16 and 18 (which have been identified also in invasive cervical carcinomas and cell lines derived therefrom), a major long term prospective study may be required to confirm this view. A factor that complicates the issue still further is the recent observation that HPV DNA of all four types has been identified in 11% of women and 5.5% of men free of disease. Infection with multiple viral types (including Types 16 and 18) was common in this apparently healthy population. Although HPV must be considered as a prime candidate for a transforming virus, current evidence suggests that the infection with the virus is per se an insufficient condition for the development of precancerous lesions or cancer of the uterine cervix and that another factor or factors may be necessary for these events to take place. Some of these possible cofactors such as age, repeated infections, and the immune status of the patient are discussed. A great deal of additional work is required before the precise role of HPV virus in the genesis of carcinoma of the uterine cervix, vulva, and vagina is firmly documented.