The majority of sexually active individuals becomes infected with human papillomavirus (HPV) at least once in their lifetime. Pathways for HPV transmission vary across different mucosal sites per individual. They include autoinoculation within one host, direct transmission between individuals (including perinatal transmission and transmission during sexual activity), and indirect transmission through contact with hands. The authors aim to clarify the prevalence and route of transmission per anatomic site, inter- and intra-individually, using a narrative review of the literature. In conclusion, transmission of HPV to the oral cavity and oropharynx is hypothesised to occur mainly through sexual contact. Transmission of particles through saliva has not been proven and daily living activities are not a documented source of HPV infection. Oropharyngeal HPV related cancer survivors and their partners do not show increased risk of infection during sexual intercourse. Transmission of HPV to the oral cavity (autoinoculation with fingers or transmission through saliva in deep kissing) is probably of limited importance.

Human papillomavirus infection (HPV) is one of the most common sexually transmitted infections and can cause penile and anal cancer in men, and invasive cervical cancer in women.

To evaulate the colonization of 32 HPV subtypes in the foreskin of boys.

A prospective analysis was made of the data of 62 healthy boys who had undergone standard circumcision. Deoxyribonucleic acid (DNA) was isolated from the foreskin tissues, and the integrity of DNA was tested. The DNA of each patient was further assessed with real-time polymerase chain reaction (PCR) and the presence of 32 subtypes of HPV was explored. To confirm the results, melting curve analysis and agarose gel electrophoresis (AGE) were performed for all samples. Further analysis was made using LCD-array on six randomly selected samples to confirm the results together with negative and positive controls.

The mean age of the boys was 6.8 ± 2 years at the time of surgery. All positive controls and samples were positive, all negative controls were negative in the first HPV amplification assay. All positive controls had typical melting curve peaks, whereas all sample amplifications had non-specific, atypical melting curves not fitting with those of the positive controls. Two bands of expected sizes (124 and 405 bp) were only observed in positive controls, but not in negative controls or samples on AGE. The same results were observed on the 6 randomly selected samples using LCD-array. Consequently, all the foreskin samples were evaluated as negative for the 32 HPV types investigated in the study.

Literature shows a high prevalence of genital HPV in newborns, in early infancy, late adolescence and adulthood. However there is a lack of data in literature on the prevalence in early and late childhood. The negative results of HPV colonization on the foreskin in the current study may be attributed to the conservative and mostly monogamous nature of most family structures in Turkey.

The results of the present study have shown that foreskin tissue is not a natural reservoir for HPV and subclinical HPV infection is not likely in the absence of suspected sexual contact.

Human papilloma viruses (HPV) are a small group of non‑enveloped viruses belonging to the Papillomaviridae family with strong similarities to polyoma viruses. The viral particles consist of a genome in the form of a circular double‑stranded DNA, encompassing eight open reading frames, as well as a non‑enveloped icosahedral capsid. HPV infection is considered the most common sexually transmitted disease in both sexes and is strongly implicated in the pathogenesis of different types of cancer. 'High‑risk' mucosal HPV types, predominantly types 16, 18, 31, 33 and 35, are associated with most cervical, penile, vulvar, vaginal, anal, oropharyngeal cancers and pre‑cancers. Screening for HPV is necessary for the prognosis and for determining treatment strategies for cancer. Novel HPV markers, including proteomic and genomic markers, as well as anti‑papillomavirus vaccines are currently available. The aim of this comprehensive review was to thoroughly present the updated information on virus development, cancer occurrence, treatment and prevention strategies, in an attempt to shed further light into the field, including novel research avenues.

The true HPV prevalence in the foreskins of infants and children has been little documented, but reporting on this prevalence is of great importance given its impact on the rationale for treating asymptomatic boys. We searched multiple databases from 1960 to 2016 for observational or prospective studies that reported on HPV prevalence in foreskins. We conducted a meta-analysis using a random-effects model to pool for HPV prevalence in the foreskins of infants and children. Eight studies, with a total of 556 infants and children with phimosis, were eligible for the meta-analysis. The pooled overall prevalence of general HPV, high-risk HPV, low-risk HPV, HPV 16/18, HPV 16, and HPV 18 were 17.3 (95%CI: 0.8-46.3), 12.1 (95% CI: 0.9-31.5), 2.4 (95% CI: 0.0-11.2), 4.8 (95% CI: 0.0-16.8), 1.7 (95% CI: 0.0-5.1), and 0 (95% CI: 0-0.5), respectively. The estimated HPV prevalence in foreskins was not zero among infants and children, which implies HPV transmission other than by sexual contact. Considering that high-risk HPV is detected in asymptomatic infants and children, future studies are warranted to determine whether preventive treatments in asymptomatic infants and children could be effective in preventing persistence or transmission of high-risk HPV.

Human papillomavirus (HPV) is composed of a particularly heterogeneous family of DNA viruses, which has gained much attention in recent years due to the discoveries of Professor Harald zur Hausen, who first identified a connection between HPV and cervical cancer. Professor Harald zur Hausen, the 'Father of HPV Virology', was the recipient of the 2008 Nobel Prize. HPV can be transmitted through physical contact via autoinoculation or fomites, sexual contact, as well as vertically from the HPV-positive mother to her newborn, causing subclinical or clinical infections. In infancy and childhood, HPV-associated clinical infections include skin warts, genital warts and juvenile recurrent respiratory papillomatosis, while cervical squamous intraepithelial lesions have also been reported among adolescent girls. To date, several research teams, worldwide, have extensively investigated HPV from the paediatric point of view. This primitive effort has been performed before the recent great expansion of paediatric HPV research due to the vaccination programmes against HPV, which were introduced into clinical practice in 2006. In this review article, we present a brief overview of paediatric HPV research after the first report in 1978 involving children in the research of HPV until the time point of this great expansion. In the future, it is expected that further unresolved issues will be addressed and clarified, as the paediatric story of HPV remains a challenging research target.

Association of High-risk Human Papillomavirus (HR-HPV) with oral cancer has been established recently. Detecting these viruses in oral cavity is important to prevent oral lesions related to them. The purpose of this study was to evaluate the prevalence of HR-HPV in the oral cavity of women with cervical cancer, and their children. A total of 70 women, previously diagnosed with cervical cancer, and 46 children of these women, born by vaginal delivery only, were selected for this study. Buccal swabs were collected from their oral cavity and HPV detection was carried out using Hybrid Capture 2 high-risk HPV (HC2 HR-HPV) detection system.

Out of 70 women with cervical cancer, four (5.71%) were found to be positive for HR-HPV in their oral cavity. No association of HR-HPV was found with sociodemographic profile, marital status, reproductive history, tobacco and alcohol usage, contraceptive pills usage, and presence of oral lesions (p>0.05). Among children, HR-HPV in the oral cavity was detected in only 1 of the 46 subjects examined (2.17%). Clinically healthy oral mucosa, without any oral lesions, was observed in all the HR-HPV positive subjects.

The result of this study showed that there is low, if any, risk of HR-HPV infection in the oral cavity of women with cervical cancer. Further, our study suggests that there is very low risk for children of women with cervical cancer, to acquire and sustain HR-HPV in their oral cavity until childhood or adolescence.

Genital warts are common and usually are harmless but can be painful and psychologically burdensome. Several local treatments can be used, including topical 5-Fluorouracil (5-FU).

To determine the effectiveness and safety of 5-FU topical treatment for genital warts in nonimmunocompromised individuals.

Databases searched were Cochrane Central Register of Controlled Trials (The Cochrane Library 2009 Issue 3), MEDLINE (1966 to August 2009), EMBASE (until August 2009), LILACS (1982 to August 2009). The search had no language or publication restrictions.

The review included randomised controlled trials (RCTs) among women, men, or both sexes, aged 18 years and older, comparing: 5-FU versus placebo or no treatment; 5-FU in any dose versus other isolated treatment, topical or systemic; 5-FU in any dose associated with other treatment versus placebo; 5-FU in any dose associated with other treatment versus other isolated treatment, topical or systemic; 5-FU in any dose associated with other treatment versus other associated treatment, topical or systemic.

Two authors independently assessed trial quality and extracted data from the original publications.

Six trials involving 988 patients (645 women and 343 men) and reporting eight comparisons were found. Two studies reported withdrawals and dropouts, but none mentioned analysis by intention to treat (ITT). 5-FU presented better results for cure than placebo or no treatment (relative risk (RR) 0.39, 95% confidence interval (CI) 0.23 to 0.67), meta-cresol-sulfonic acid (MCSA) (RR 2.11, 95% CI 0.83 to 5.37), Podophylin 2%, 4% or 25% (RR 1.26, 95% CI 0.86 to 1.82). There were no statistical differences for treatment failure for 5-FU versus CO2 Laser (RR 0.69, 95% CI 0.43 to 1.11) versus 5-FU + INFalpha-2a (low dose) (RR 1.02, 95% CI 0.87 to 1.119). Worse results were found for 5-FU versus 5-FU + INFalpha-2a (high dose) (RR 10.78, 95% CI 1.50 to 77.36), and 5-FU + CO2 Laser INFalpha-2a (high dose) (RR 7.97, 95% CI 2.87 to 22.13).

The reviewed trials were highly variable in methods and quality, and the evidence provided by these studies was weak. Cure rates with several treatments were variable, and although 5-FU presents therapeutic results that are inferior to those seen with 5-FU + Inf alpha-2a (high dose) and 5-FU + CO2 Laser + Inf alpha-2a (high dose), the treatment should not be abandoned. Topical treatment with 5-FU has a therapeutic effect; however, the benefits and risks have not been determined clearly and further studies are needed.

The objectives of this study were to delineate the clinical characteristics of a hospital-referred pediatric population infected with anogenital warts and to investigate the possible relationships between human papillomavirus types and the identified clinical characteristics. Over a 7-year period, 72 patients under the age of 12 years were seen at our dermatology clinic for anogenital warts, corresponding to a prevalence of 1.7/1000 in our patient population. Sixty-four percent (46/72) were girls. Congenital, prenatal, ascending infections occurred in two subjects. The onset of anogenital warts occurred before age 2 in 28% and between 2 and 6 years of age in 62% of children and tended to be younger in boys. We identified unusual cutaneomucosal serotypes human papillomavirus 7 and 57 (three and eight instances, respectively). The modes of transmission of anogenital warts in children cannot be identified either by the clinical appearance of the lesions or by human papillomavirus typing. We conclude that the best way to identify possible sexual abuse is still by history taking, careful assessment of the socio-clinical context, and physical examination.

Human papillomaviruses (HPVs) are small DNA tumour viruses associated with a variety of proliferative diseases. More than 100 types have been identified and can broadly be grouped into cutaneous and mucosal types according to their site of infection, and can be further subdivided into low-risk (LR) and high-risk (HR) types depending upon their association with malignancy. The main route of transmission of HR mucosal HPVs is through sexual contact, although the acquisition of virus cannot be entirely explained by this mode alone. Evidence also exists for horizontal transmission by other routes and vertical transmission. HR HPVs, particularly HPV-16, have been detected in oral swabs from newborns, infants and children. Such alternative modes of transmission and acquisition may have an important impact in several areas, including vaccination strategies, epidemiological studies, and the clinical management of children with HPV-associated diseases. This article reviews the literature describing the detection of HPV infections during infancy and childhood and provides evidence for a role of vertical transmission in the spread of HPV infection.

The purpose of this study was to determine the frequency of human papillomavirus (HPV) infections in the normal oral cavity of children in Japan. Oral squamous cell specimens were collected from 77 children (44 boys and 33 girls), aged 3 and 5 years. Extracted DNA was evaluated for HPV infections by polymerase chain reaction (PCR) methods, using consensus primers for the L1 region, specific primers, and direct DNA sequencing analysis. Thirty-seven of 77 specimens (48.1%) were positive for HPV DNA. Positive rates of boys and girls in all specimens were 28.3 (22/77) and 19.5 (15/77)%, respectively. The positive rate in 3-year-old children was 45.2 (14/31)%, and positive rates in boys and girls were 52.6 (10/19) and 33.3 (4/12)%, respectively. The positive rate in 5-year-old children was 50.0 (23/46)%, and positive rates in boys and girls were 48.0 (12/25) and 52.4 (11/21)%, respectively. HPV types were determined by specific PCR and direct DNA sequencing analysis. Frequent HPV types in the specimens of all children were HPV-16 (11/37; 29.7%),-1 (6/37; 16.2%),-2 (6/37; 16.2%),-75 (6/37; 16.2%). The results of the present investigation indicate that many HPVs, including HPV-16 (a high-risk type for cancer), are present in the oral cavity of 3- and 5-year-old children. It is suggested, therefore, that the oral cavity is already a reservoir of HPVs in childhood where later HPV-associated diseases, such as oral cancer and other oral lesions, may develop.

To date, more than 100 types of human papillomavirus (HPV) have been identified. In the past 20 years, there has been an increasing interest in HPVs because of their potential role in the pathogenesis of malignant tumors. HPV infections are known to affect predominantly adult, sexually active age groups, whereas skin warts, at various anatomic sites, are usually associated with younger individuals. The modes of viral transmission in children remain controversial, including perinatal transmission, auto- and hetero-inoculation, sexual abuse, and, possibly, indirect transmission via fomites. Recent studies on perinatal infection with HPV have been inconclusive. It is still unclear how frequently perinatal infection progresses to clinical lesions, whether genital, laryngeal, or oral. Conflicting reports have been published on the prevalence of HPV infections in children. The current consensus is, however, that newborn babies can be exposed to cervical HPV infection of the mother. The detection rate of HPV DNA in oral swabs of newborn babies varies from 4% to 87%. The concordance of HPV types detected in newborn babies and their mothers is in the range of 57% to 69%, indicating that the infants might acquire the HPV infection post-natally from a variety of sources. HPV antibodies have been detected in 10% to 57% of the children, and there is usually no correlation between seropositivity and the detection of HPV DNA in either the oral or the genital mucosa. There is also evidence that transmission in utero or post-natal acquisition is possible. The mode of in utero transmission remains unknown, but theoretically the virus could be acquired hematogenously, by semen at fertilization, or as an ascending infection in the mother. The understanding of viral transmission routes is important, particularly because several vaccination programs are being planned worldwide. The serologic response to HPV detected in different populations of young women or women at risk of cervical cancer might be due to genital infections, but the possibility that HPV infection has been acquired earlier in life through the oral mucosa or respiratory tract cannot be ruled out.

The purpose of this pilot study was to determine the frequency of human papillomavirus (HPV) in the oral cavities of children and adolescents and to identify potential risk factors for HPV infection.

Sociodemographic information was obtained on 268 healthy infants, children, and adolescents who were < or = 20 years old. Oral squamous cells were collected from swabs with young children and from oral saline solution rinses with older children and adolescents. Extracted DNA was evaluated for HPV by polymerase chain reaction, dot blot hybridization, and DNA sequencing. Factors associated with the presence of HPV were tested by using chi(2), Fisher's exact test, and logistic regression tests.

HPV was detected in 6.0% of the participants. HPV frequency among young children (<7 years old) was 8.7% (11/127), and among adolescents (13-20 years old) it was 5.2% (5/97). HPV was not detected in children aged 7 to 12 years old (0/44). Fifty-four percent (6/11) of HPV-positive children were 1 year of age or less; 3 of the HPV-positive children (<7 years old) were delivered by cesarean section. No statistically significant association was found between the detection of HPV in the oral cavity and method of delivery or gender; parent's race, education, HPV-related conditions, smoking history, or number of sex partners; or adolescent's smoking history or history of sexual activity.

This study suggests that HPV is present in the oral cavity primarily in children 2 years old and younger and in adolescents 13 years and older. Cesarean delivery was not protective against oral HPV infection; in fact, half of the HPV-positive infants were born by cesarean delivery.

The recent gain in knowledge of the genomic function of HPV has led to a greater understanding of the natural history of HPV infection in women, starting from infection to the development of invasive cancer. LSIL is reflective of a benign process associated with HPV replication, and in the majority of women, HPV is eradicated or put into some type of immunologic control so that it remains undetected. In contrast, in the minority of women who have persistent infection, HSIL and invasive cancer are more likely to occur. These findings can be translated clinically to suggest that LSIL can be followed up for a defined period of time and that HPV testing in older women may be useful to identify persistent HPV infections and subsequent risk for invasive cancers.

It is well recognised that high-risk human papillomaviruses (HPVs) are spread by sexual activity, but the possibility of non-sexual transmission remains controversial. We present evidence for vertical transmission from at least 30% HPV positive mothers to their infants, resulting in persistent infection in children. That the mother is the source of infant infection has been confirmed by DNA sequencing. We also discuss the evidence for oral HPV-16 infection in children. In our own studies, HPV-16 DNA was detected in buccal cells from 48% children, aged 3-11 and transcriptionally active infection was confirmed in some children. Other studies have reported prevalences of 19%-27% among children less than 11 years of age. Studies that have failed to detect high-risk HPVs in children have used techniques which were insufficiently sensitive to detect the low levels of virus present. Serological studies also suggest that < or = 45% prepubertal children have acquired HPV-16. Thus, convincing evidence is now available for vertical transmission of high risk HPVs, which probably results in widespread infection among children. The consequences of such infections remain to be elucidated.

To evaluate for the presence of subclinical human papillomavirus (HPV) in cases of suspected sexual abuse in children.

Prospective data collection via interviews, physical examination, colposcopic examination, and tissue sampling by a surface swab technique.

A total of 40 pediatric patients ranging in age from 1 to 16 years who were referred to the Special Assessment and Management Clinic at Cardinal Glennon Children's Hospital, St Louis, MO, for probable or confirmed sexual abuse.

In addition to colposcopic examination for physical signs of abuse, the patients were screened for evidence of sexually transmitted diseases, including syphilis, gonorrhea, and Chlamydia. At that time, surveillance sampling of the throat, vaginal introitus, and/or rectum by a simple, rapid surface swab technique was performed to detect the presence of HPV.

Template DNA was extracted from cotton swabs and analyzed using polymerase chain reaction analysis.

Human beta-globin sequences were detected in 58 (83%) of 70 specimens obtained from 40 patients, indicating successful processing had occurred. Using a consensus L1 primer-probe set capable of detecting multiple HPV genotypes, 2 (3%) of 58 samples from 2 (5%) of 40 patients were positive for HPV 16. None of the other 56 specimens yielded evidence of HPV. Appropriate positive and negative controls were included in each assay.

Our results suggest that subclinical HPV infection is possible, but not commonly associated with sexual abuse in children from St Louis, MO. In this group of children without condyloma, HPV 16 was the only type identified.

The purpose of this study was to determine the potential for human papillomavirus to be transmitted vertically.

We started a systematic study of children 0.3 to 11.6 years old born to mothers included in the cohort of 530 women prospectively followed up for genital human papillomavirus infections in Kuopio since 1981. So far 98 children have been examined. The examinations included medical history, clinical examination of the oral cavity and hand warts, and cytologic samples from the oral mucosa for detection of human papillomavirus deoxyribonucleic acid with polymerase chain reaction with subsequent Southern blot hybridization.

Human papillomavirus deoxyribonucleic acid was found in 31 of the 98 (31.6%) oral scrapings. with MY09 and MY11 human papillomavirus primers, 12 of the 98 were positive for human papillomavirus deoxyribonucleic acid in the electrophoresis gel and in subsequent hybridization. Nineteen of the positive samples were not visible in the gel but become positive when hybridized. At delivery, 5 mothers had genital human papillomavirus infection with the same virus type found in her child. In the additional 11 mothers genital human papillomavirus infection with the same virus type as in the child was diagnosed a few months before or after delivery. Mothers of the 25 children shown to be negative for oral human papillomavirus were also human papillomavirus deoxyribonucleic acid negative at delivery. Minor hyperplastic growths of the oral mucosa were found in 21 of the 98 children (21%). One child had a papilloma where human papillomavirus 16 deoxyribonucleic acid was detected, as was also found in her mother's genital area at delivery.

Our results support the concept that an infected mother can transmit human papillomavirus to her child.

Epidemiologic and laboratory data suggest that cervical cancer typically arises from a series of causal steps. Each step can be studied separately in the hope of better etiologic understanding and improved cancer prevention. The earliest identified etiologic step is infection of young women with specific types of venereally transmissible human papillomaviruses (HPVs). Cervical HPV infections often lead to low grade squamous intraepithelial lesions (mildly abnormal Pap smears). Human papillomavirus infections and their associated lesions are extremely common among young, sexually active women. The infections typically resolve spontaneously even at the molecular level within months to a few years. Uncommonly, HPV infections and/or low grade lesions persist and progress to high grade lesions. The risk factors for progression are mainly unknown but include HPV type and intensity, cell-mediated immunity, and reproductive factors. Nutritional factors or co-infection with other pathogens may also be involved at this apparently critical etiologic step between common low grade and uncommon high grade intraepithelial lesions. Except for advancing age, no epidemiologic risk factors have been found for the next step between high grade intraepithelial lesions and invasive cancer. At the molecular level, invasion is associated with integration of viral DNA. Based on worldwide research, the steps in cervical carcinogenesis appear to be fundamentally the same everywhere, with a central role for HPV infection. The importance of etiologic cofactors like smoking, however, may vary by region.

Perinatal transmission of genital human papillomaviruses (HPVs), including HPV-16 and -18 which are associated with anogenital carcinomas have been described previously [Pakarian et al. (1994): British Journal of Obstetrics and Gynaecology 101:514-517; Kaye et al. (1994) Journal of Medical Virology 44:415-421]. A study was undertaken to investigate whether HPV-16 and -18 DNA in infants contaminated at delivery persists until they are 6 months of age. Of 61 pregnant women recruited, 42 (68.8%) were HPV-16 and 13 (21.3%) were HPV-18 DNA positive. At 24 hr there were transmission rates from HPV DNA positive mothers to their infants of about 73% (HPV-16: 69%; HPV-18: 76.9%). Ten mothers who were both HPV-16 and -18 DNA positive produced six (60%) infants who were also doubly positive at 24 hr. HPV DNA persisted to 6 weeks in 79.5% (HPV-16: 84%; HPV-18: 75%) of those infants who were positive at birth. At 6 months of age, persistent HPV-16 DNA was detected in 83.3% of cases, but HPV-18 DNA persistence at this time was 20%. To extend these observations over a greater age range of children HPV-16 L1 and L2 proteins were expressed in insect cells via recombinant baculoviruses and sera from 229 children were examined to determine at what age IgM antibodies to HPV were acquired. There was a bimodal distribution of IgM seropositivity which peaked between 2 and 5 and 13 and 16 years of age, suggesting that two distinct modes of transmission may occur. The observation that infection with high cancer risk genital HPVs may occur in early life and persist is of considerable importance for HPV vaccine strategies.

The authors present a study of five cases of vulvar congenital papillomas and papillomatoses in stillborns and neonates dead upon birth. The studied material was collected from five necropsies. The histopathological evaluation showed hyperkeratosis, acanthosis, papillomatosis, perinuclear haloes, and nuclear abnormalities. In three of the cases, the electron microscopy identified nuclear and cytoplasmatic viral particles ranging from 40 to 60 nm in size, compatible with HPV. The immunohistochemical study of those lesions showed nuclear and cytoplasmatic positivity. The authors concluded that the presence of viral particles suggestive of HPV added to the immunopositivity indicated the possibility of viral infection.

Biopsy material from 20 oral lesions (19 condylomas and 1 squamous papilloma) previously shown to contain human papillomavirus (HPV) 6 and HPV 11 sequences by in situ hybridization were examined using 3 commercially available HPV typing kits. Sensitivity and specificity were compared with in-house methods. Previous in situ hybridization had detected HPV 6b in 11 (55%) of the biopsies, HPV 6 and 11 in 7 (53%) and HPV 11 alone in 1 biopsy. Only one of the commercial assays (assay 1) detected HPV in all 20 biopsies (11 positive for HPV 6b only, 1 for HPV 11 only and 7 for HPV 6b and 11). The wide spectrum probe of assay 2 detected HPV in only 10 (50%) of the biopsies, and in a further 2 biopsies the hybridization results were difficult to interpret because of background staining. Assay 3 used a combined HPV 6/11 probe and detected HPV in 15 (75%) of the biopsies. Clear hybridization signals were demonstrated in the intermediate and upper layers only of squamous epithelium, as expected from the known association of HPV replication with epithelium differentiation. In most specimens background levels were not a problem, and all commercial assays were easy to use. The findings are discussed in the context of the digestion procedures, sensitivity of the probes provided and the conditions of hybridization, all of which would influence the detection of HPV.

Human papillomavirus infections in children, particularly when occurring as condylomata acuminata, present a difficult and often puzzling problem. The possibility that the lesions were acquired through sexual contact mandates a careful and thorough evaluation. Even then, the source of the infection may be elusive because of a long latency between inoculation and the development of lesions, the secretive milieu of childhood sexual abuse, and lack of data about modes of transmission. New molecular techniques of HPV DNA detection and typing have not proven to be helpful in determining the source of the infection but may assist in identifying children who are at risk for the development of carcinoma. Various treatment modalities have been attempted with a significant percentage of recurrences. Many unanswered questions remain regarding the biology and epidemiology of HPV in children and adults. Clinical and basic science research specifically designed to address the concerns of the pediatric age group is urgently needed.

During a long term experiment designed to identify the contribution of bovine papillomavirus type 4 (BPV-4), environmental mutagens and immunosuppressants to the development of carcinomas of the upper alimentary tract of cattle, there was evidence of latent papillomavirus infection. Papillomatosis-free animals, when immunosuppressed either by feeding bracken fern or by azathioprine treatment, developed skin warts containing either BPV-1 or BPV-2. Skin warts appeared also in an immunocompetent animal at sites of damaged skin. It was concluded that the animals harboured latent papillomavirus which was reactivated by immunosuppression and/or physical trauma, causing skin warts. Papillomavirus DNA was also detected in lymphocytes of both experimental and control animals, suggesting that one of the sites of latency may be the circulating lymphocyte.

To identify the prevalence of HPV DNA using the polymerase chain reaction (PCR) in neonatal foreskin and cervical specimens obtained at necropsy.

Foreskin and cervical specimens were obtained from consecutive neonates who had autopsies performed at The Royal Women's Hospital, Melbourne, from June 1991 to February 1992. Specimens were analysed for HPV DNA using the polymerase chain reaction and the L1 consensus primers and generic probes.

Specimens were obtained from 98 neonates, 52 males and 46 female. The mean gestational age of the neonates was 29 weeks (range 20-42). Eighty neonates died in utero, three during labour and 15 following delivery. Ninety four were delivered vaginally whilst four were delivered by caesarean section. Samples were collected a mean of 20 hours (range 2-48) from the time of delivery. In 30 cases there was evidence of autolytic change while in the remaining cases, the histology was well preserved. No evidence of HPV DNA was found in any of the samples using the L1 general primers (95% confidence interval 0-3.6%). Recent cervical cytology was available on 70 of the infant's mothers. Six had cytological evidence of HPV infection while the remainder were normal.

HPV DNA is uncommonly detected (by PCR) in foreskin and cervical specimens obtained from neonates.

To assess the presence of human papillomavirus (HPV) DNA in urethral and urine specimens from men with and without sexually transmitted diseases.

Prospective study.

Two London departments of genitourinary medicine

100 men with urethral gonorrhoea, 31 men with penile warts and 37 men with genital dermatoses.

Urethral and urine specimens were taken, HPV DNA extracted and then amplified using the polymerase chain reaction. HPV types 6, 11, 16, 18, 31 and 33 were identified using Southern blotting followed by hybridisation.

HPV DNA was detected in 18-31% of urethral swab specimens and in 0-14% of urine specimens. Men with penile warts had HPV detected in urethral swabs more often than did men in the other two clinical groups. "High risk" HPV types were found in 71-83% of swab specimens and in 73-80% of urine specimens containing HPV DNA.

HPV is present in the urogenital tracts of men with gonorrhoea, penile warts and with genital dermatoses. In men with urethral gonorrhoea, detection of HPV in urethral specimens is not related to the number of sexual partners, condom usage, racial origin or past history of genital warts. HPV DNA in the urethral swab and urine specimens may represent different aspects of the epidemiology of HPV in the male genital tract. The preponderance of HPV types 16 and 18 in all three groups of men may be relevant to the concept of the "high risk male".

We studied 25 children, age 7 months to 12 years 6 months, with anogenital warts, and their parents. In most children the warts were localized in the anal area, in 3 of 18 girls perianally and on the vulva, and in 4 girls exclusively on the vulva. Southern blot hybridization studies disclosed an association of condylomata with human papillomaviruses (HPV) 6 and 11 in 74% and HPV 2 in 17.4% of patients. The clinical features were similar in warts induced by genital and cutaneous HPVs. Even the HPV 2-associated warts in the vulva of two girls were typical of condyloma acuminatum. In all children with HPV 2-induced condylomata, cutaneous common warts coexisted, also induced by HPV 2. However, three mothers had cutaneous warts, and the children's condylomata were associated with HPV 6. Thus, the mere presence of skin warts in family members does not rule out other sources of infection. Sexual abuse was suspected in four girls and two boys, but was not confirmed in any. Nonsexual transmission could occur by persons with the lesions taking care of children. Perinatal transmission also appears to be an important route of infection in small babies. Infection in utero was probable in one girl in whom anal warts appeared in the first week of life and whose mother had cervical condylomata during pregnancy. This study provides further confirmation of possible nonsexual transmission of genital HPVs and the not infrequent association of childhood condylomata with HPV 2.

Increasing evidence indicates that infection with genital types of human papillomavirus (HPV) can occur prior to the onset of sexual activity, possibly by perinatal transmission. Evidence is also accumulating that women infected with the human immunodeficiency virus (HIV) more frequently express HPV. We conducted this study to measure HPV prevalence in HIV-seropositive and -seronegative women in Kinshasa, Zaire and in their children. We collected cervico-vaginal lavage specimens from 80 mothers (52 HIV-seropositive and 28 HIV-seronegative at the time of delivery) and oropharyngeal and perineal specimens from their 81 3-year old children (21 HIV-seropositive and 60-seronegative). We used the ViraPap and ViraType assay to test specimens for HPV DNA by the dot-blot technique. Detection of HPV in the mother was highly associated with HIV: 20 HIV-seropositive women and one seronegative woman had HPV DNA. Ten children had HPV DNA. However, detection of HPV in the children was not associated with the mothers' HPV or HIV status or with the child's own HIV status. These findings document a substantial prevalence in young children of HPV DNA types that are linked to genital-tract neoplasia in adults, but do not specifically support a hypothesis of mother-to-child transmission of genital HPV types.

In an attempt to assess the multifocal nature of anogenital HPV infection in men, skin biopsies, urethral swabs and urine specimens were obtained from 100 men with genital dermatoses. The specimens were examined for the presence of human papillomavirus (HPV) types 6, 11, 16, 18, 31 and 33 using the polymerase chain reaction and Southern blotting techniques. HPV DNA was detected in one or more specimens from 39 patients, that is 29 of 100 biopsy specimens, 21 (25%) of 85 urethral swab specimens and 6 (10%) of 59 urine specimens. HPV DNA was more common in men with at least 20 lifetime sexual partners and in those who gave a history of anogenital warts. Twelve (18%) of 66 biopsy specimens with no histological evidence of warty change or neoplasia had detectable HPV DNA. HPV DNA was detected no more frequently in the urethral and urine specimens from men with histological evidence of warts or neoplasia than from men without such changes. HPV types 6 and 11 were most common in biopsy specimens with histological changes of typical HPV infection. HPV type 16 was commonest in biopsy specimens with neoplasia and type 18 with other changes. Furthermore, 'high-risk' HPV types were found proportionately more often in urethral swab and urine specimens than in biopsy specimens. There was generally a poor correlation between the detection of HPV DNA at the different sites. A greater understanding of the role of HPV in the production of genital abnormalities is required in order to develop a rational approach to the management of these patients.

A 79-year-old virgo intacta presented with a 20-year-history of intertrigo, and a 3-month history of superimposed warty masses beneath both breasts and in the groin and perianal areas. There was no evidence of immunosuppression. Histology of the warty lesions showed squamous papillomata, with evidence of wart virus infection. Human papillomavirus (HPV) type 6 was identified by in situ DNA hybridization, in the submammary lesions. This is an unusual manifestation of both intertrigo and wart virus infection. HPV-6 is classically found in anogenital warts. We assume that these warts were acquired by a non-venereal route and/or by congenital infection some 78 years ago. We suggest that it is the warm, moist environment, rather than the specific site, which encourages HPV-6 to flourish.

Human papillomavirus type-16 (HPV-16) is strongly associated with cervical carcinoma and cervical intraepithelial neoplasia. It may soon be possible to develop prophylactic vaccines designed to induce neutralizing antibodies to HPV-16 virions in genital secretions and therapeutic vaccines to induce cytotoxic T-cell responses against HPV-16 early proteins in cervical intraepithelial neoplasia and cervical cancers. Although significant advances have been achieved, problems remain before such vaccines can be used routinely.

A series of 71 surgically resected esophageal squamous cell carcinomas, including 51 cases of formalin-fixed samples and 20 cases of fresh biopsy specimens derived from the high-incidence area of esophageal cancer in China, were systematically analyzed for the presence of human papillomavirus (HPV) infections by light microscopy, electron microscopy (TEM), in situ DNA hybridization, Southern blot hybridization, and polymerase chain reaction (PCR) techniques. On light microscopy, HPV-suggestive lesions were found in a total of 49.0% (25 of 51) of the specimens, including the flat type (22 of 51) and, less frequently, an inverted one (2 of 51). Of the 51 formalin-fixed, paraffin-embedded specimens, 43.1% (22 of 51) contained HPV DNA sequences by in situ hybridization. Of the positive cases, HPV 6 was present in three (5.9%), HPV 11 in three (5.9%), HPV 16 in eight (15.7%), HPV 18 in six (11.8%), double infections with HPV 11/18 in one (2.0%), and HPV 16/18 in one. In most cases the HPV-positive signals were localized in the hyperplastic and/or dysplastic epithelium adjacent to invasive carcinomas. In two specimens, however, HPV DNA sequences were found in the frankly invasive lesions, one being HPV 6 and the other HPV 18. On TEM, HPV-like particles located in the nuclei of koilocytotic cells were demonstrated in two of the five specimens previously shown to be HPV-positive by in situ hybridization. By means of the PCR technique, all specimens positive for HPV by in situ hybridization also contained amplified HPV sequences. Moreover, three additional samples negative by in situ hybridization were found to contain HPV 11 DNA sequences. Of the 20 DNA samples extracted from the fresh carcinoma samples (containing some surrounding tissues as well) 9 were shown to contain HPV DNA sequences by Southern blot hybridization under low-stringency conditions. Of these, eight samples remained positive when hybridized with the probe cocktail of HPV 11, 16, 18, and 30 DNA under high-stringency conditions. HPV DNA sequences in these carcinoma specimens appeared to be present mainly in an integrated form. The present results confirm the HPV involvement in esophageal squamous cell lesions and suggest that HPV infection might be an important etiologic factor in the pathogenesis of esophageal cancer, most probably acting synergistically with other carcinogenic factors.

The objective of this study was to examine the possibility of intrauterine human papillomavirus infection of fetuses by transplacental transmission of human papillomavirus before delivery.

Specimens of cervicovaginal cells and peripheral blood mononuclear cells were obtained from 52 consecutive pregnant women in the third trimester of pregnancy. Cord blood specimens were also obtained from the neonates born to these mothers. Presence of human papillomavirus types 16 and 18 deoxyribonucleic acid was analyzed by an in vitro enzymatic deoxyribonucleic acid amplification method.

Human papillomavirus type 16 deoxyribonucleic acid was found in 6 (11.5%) cervicovaginal and in 9 (17.3%) peripheral blood mononuclear cell specimens. Seven cord blood specimens from neonates born to mothers who were positive for peripheral blood mononuclear cell human papillomavirus type 16 deoxyribonucleic acid were found to contain human papillomavirus type 16 deoxyribonucleic acid. One cervicovaginal and two peripheral blood mononuclear cell specimens contained human papillomavirus type 18 deoxyribonucleic acid, but none of the cord blood specimens contained human papillomavirus type 18 deoxyribonucleic acid.

These results seem to suggest possible transplacental transmission of the virus and the potential association of such transmission with the status of human papillomavirus in peripheral blood mononuclear cells.