Human papillomaviruses 6/11, 16/18 and 31/33/51 are not associated with squamous cell carcinoma of the urinary bladder

OBJECTIVE: To assess high-risk human papillomavirus (HPV), mainly HPV type 16, 18, 31 and 33 (an important aetiological factor in squamous cell carcinoma, SCC, of the anogenital region) in SCC of the urinary bladder. MATERIAL AND METHODS: Sixteen SCC from the urinary bladder were evaluated using non-isotopic in situ hybridization with a sensitive detection system for the presence of high-risk HPV 16/18, or 31/33/51, and for HPV6/11, a low-risk type commonly found in condylomata. Previously published studies were also reviewed and assessed. RESULTS: No high-risk HPV was found in any of the SCC of the bladder evaluated. Previous reports identified nine HPV-positive SCC of a total of 105, including the present series. In four of these positive cases, HPV types were found that are considered a high risk in anogenital carcinomas. CONCLUSION: From the present and previous results, we conclude that HPV has no major role in the pathogenesis of SCC of the urinary bladder.     

Carcinosarcoma of the uterine cervix: a report of eight cases with immunohistochemical analysis and evaluation of human papillomavirus status

Carcinosarcomas (malignant Müllerian mixed tumors [MMMTs]) of the uterine cervix are rare neoplasms. This report describes the morphology, immunohistochemical profiles, and human papillomavirus (HPV) status of eight cervical MMMTs. Patients' ages ranged from 32 to 93 years (mean, 61 years). Seven cases showed in situ squamous cell carcinoma (SCC). The invasive epithelial component (EC) was composed of combined adenoid basal carcinoma, basaloid SCC, and adenoid cystic carcinoma (ACC) in two cases. Keratinizing SCC, large cell nonkeratinizing SCC, undifferentiated carcinoma, and basaloid SCC predominated in the remaining tumors, one of which had admixed ACC. The sarcomatous component (SC) was homologous and spindled with admixed myxoid areas in three lesions. The ECs and SCs in six MMMTs showed dual immunostaining with epithelial membrane antigen and the pan-keratin marker, MNF116. The SC was vimentin-positive in seven cases. Five tumors had a vimentin-positive EC. The SC was positive for muscle specific actin and/or smooth muscle actin in seven lesions, of which four were desmin-positive. Polymerase chain reaction (PCR) using GP5+/GP6+ L1 consensus primers detected HPV DNA in all eight cases. Nonisotopic in situ hybridization with digoxigenin-labeled probes to HPV types 6, 11, 16, 18, 31 and 33 demonstrated integrated HPV 16 in three cases, not only in the EC, but also in nuclei of the SC. This is the first study to implicate HPV in the evolution of cervical MMMTs. The above observations lend support to a metaplastic theory of histogenesis.     

膀胱癌患者阴毛毛囊人乳头瘤状病毒的检测分析

目的人类乳头瘤状病毒（human papillomavirus，HPV）与膀胱癌关系密切，HPV在膀胱癌组织中的检出率很高，但其感染途径尚不清楚，本文旨在明确膀胱癌患者阴毛毛囊HPV的感染情况。方法PCR体外扩增和DNA反向点杂交相结合的DNA芯片技术测定19例膀胱尿路上皮细胞癌患者和30例健康人阴毛毛囊HPV感染情况。结果19例膀胱尿路上皮细胞癌患者的阴毛毛囊有2例发现HPV感染，HPV感染的亚型为HPV6和HPV18，HPV的感染率为10．5％；30例健康人中2例阳性，其亚型均为HPV6，感染率为6．7％。结论膀胱尿路上皮细胞癌患者阴毛毛囊不是膀胱癌组织中HPV的感染途径（P〉0．05），推测膀胱癌组织HPV感染的途径可能为通过尿道逆行感染。     

High-risk human papillomavirus types and squamous cell carcinoma in patients with respiratory papillomas.

Respiratory papillomas (RPs) are benign, virally induced tumors of the larynx and respiratory epithelium that may obstruct the airway and tend to recur frequently. RPs are thought to be the result of infection with the human papillomaviruses (HPVs) types 6 and 11. We surveyed archival RP specimens to determine whether there were correlations of HPV type with patient characteristics or clinical course. Paraffin-embedded papilloma specimens of 45 different patients were analyzed. We assessed HPV types using the polymerase chain reaction with E6 consensus primers, hybrid capture assays (high or low risk), and dot blot hybridization of generic E6 PCR products with E6 type-specific oligonucleotide probes. The presence and type of HPV were correlated with patient data from a retrospective chart review. We found that RPs may have either low- or high-risk HPV types and some contain multiple HPV types. Respiratory infection with high-risk HPV apparently introduces a long-term risk of squamous cell carcinoma development, even in the absence of conventional cofactors. Low-risk HPV infection may also act in association with these cofactors to promote carcinogenesis. Our data also show a racial imbalance in RP that may indicate a difference in genetic resistance and/or susceptibility to HPV infection and the development of RP.     

Association of Human Papillomavirus Type 11 with Carcinoma of the Penis

Human papillomaviruses (HPVs) are epithelium-tropic viruses associated with several cutaneous, epithelial, and mucosal lesions. The oncogenic potential varies considerably among the more than 70 different genotypes so far identified. HPV 6 and 11 are generally found in benign genital condilomata or laryngeal papillomas, but they have been sporadically associated with genital malignancies. Polymerase chain reaction (PCR) primed by degenerated consensus oligonucleotides (from a late region of the HPV genome) allows one to amplify a broad spectrum of HPV, whereas the amplification with specific primers is restricted to a limited number of HPVs. Therefore, the restriction fragment length polymorphism assay permits one to identify the HPV type present in the PCR product. We report a case of an invasive verrucous carcinoma of the penis associated with HPV 11, a type previously considered noncarcinogenic.     

The distribution of low and high-risk HPV types in vulvar and vaginal intraepithelial neoplasia (VIN and VaIN)

It has been proposed that low-grade vulvar and vaginal lesions (VIN 1 and VaIN 1) are flat condylomas and should be designated as such. Moreover, their relationship to high-grade lesions (VIN 3 and VaIN 3) is unclear. Accordingly, this study was undertaken to address these issues by comparing the distribution of human papillomavirus (HPV) types in vulvar and vaginal intraepithelial lesions. We identified 33 cases of VIN 1, 34 cases of VIN 3, 17 cases of VaIN 1, and 16 cases of VaIN 3. In addition, 36 cases of low-grade squamous intraepithelial lesion (LSIL) in the cervix and 116 cases of cervical high-grade squamous intraepithelial lesion were used for comparison. Polymerase chain reaction analysis was performed using both the Roche PGMY and DDL SPF 10 systems. In cases where HPV was detected, the majority of low-grade and high-grade lesions contained a single HPV type. However, a minority of cases were found to have multiple HPV types. Of the VIN 1 cases, a low-risk virus was seen in 22 (67%), with HPV 6 or 11 accounting for 14 (42%). A high-risk virus was detected in 14 (42%) of cases of which 2 (6%) contained HPV 16. Of the VIN 3 cases, all had high-risk HPV of which 31 (91%) were found to have HPV 16. Of the VaIN 1 cases, 6 (35%) were found to have low-risk HPV types. HPV 6 or 11 were not found in these cases. High-risk virus was seen in 13 (76%) VaIN 1 cases, with 1 (6%) containing HPV 16. HPV was detected in 15 of 16 (94%) VaIN 3 lesions, all of which had high-risk types. HPV 16 was found in 8 (50%). In contrast, 2 (6%) of cervical LSIL had low-risk HPV (HPV 6 and 11), whereas 34 (94%) of LSIL cases had high-risk HPVs. Of the cervical high-grade squamous intraepithelial lesion cases, 100% had high-risk HPVs of which 87 (75%) were found to have HPV 16. The findings demonstrate that a significant number of low-grade vulvar and vaginal lesions contain high-risk HPV types, supporting their designation as low-grade intraepithelial lesions rather than flat condylomas. The low frequency of HPV 16 in VIN 1 compared with VIN 3 suggests they are distinct lesions or that HPV 16 is critical in the progression to VIN 3. Finally, comparison of the distribution of HPV in the vagina and vulva suggests that VaIN is more closely related to cervical intraepithelial neoplasia than to VIN.     

Human papillomavirus DNA in malignant and hyperplastic prostate tissue of black and white males

This study hypothesized that human papillomavirus (HPV) infection is associated with increased prostate cancer risk, and that the 40% higher incidence rate in blacks is attributable to a greater prevalence of oncogenic viral DNA in prostatic tissues. Viral L1 and E6 gene sequences were polymerase chain reaction (PCR) amplified in archival tissues from 56 prostate cancer cases and 42 hyperplastic controls. L1 amplimers were hybridized by dot blot to HPV L1 generic probes, as were E6 amplimers to E6 probes specific for HPV 6, 11, 16, 18, 31, 33, and 45. 12.5% of cases and 9.5% of controls were HPV positive by L1 hybridization (age/race adjusted odds ratio = 1.66, 95% confidence interval = 0.33, 8.37). Four of 52 (7.7%) blacks were HPV positive compared to 7 of 46 (15.2%) whites. However, none of the L1-positive samples hybridized to the E6 type-specific probes, and positive results were not replicable using a broader spectrum of PCR primers and probes. These data suggest that HPV infection is not a significant risk factor for prostate cancer and does not explain the excess cancer risk in blacks. © 1996 Wiley-Liss, Inc.     

Papillomas of the External Ear Canal: Report of Ten cases in Chinese Patients with HPV In Situ Hybridization

Squamous papilloma is a benign exophytic proliferation which can occur occasionally in the external ear canal. It is widely assumed that the Human Papilloma Virus (HPV) is an etiologic factor of papillomas. Available techniques for detection of HPV genomes include immunohistochemistry, Southern blot hybridization, in situ hybridization (ISH), and polymerase chain reaction. To our knowledge, HPV typing has not been reported on tissue sections of papillomas in the external ear canal. We report HPV ISH analysis in ten cases of papillomas, involving the external ear canal in Chinese patients. These papilloma excrescences were less than 1 cm in diameter, and were benign morphologically. Automated HPV ISH analysis was performed for the hybridization of DNA probes, including both low-risk and high-risk HPV subtypes. HPV ISH results revealed that seven out of ten cases were positive for low-risk HPV (6, 11), three cases demonstrated no hybridization for low-risk HPV probe, and none of the cases revealed any detection of high-risk HPV (16, 18, 31, 33, 35, 39, 51, 52, 56, 58, and 66). On follow-up after 18–29 months (average 24.5 months), eight patients were doing well, with no local recurrence after excision. Two patients were lost to follow-up. Our results confirm that benign papillomas of the external ear canal are associated with low-risk HPV infection with benign behavior and neither recurrence nor high grade dysplasia.     

Human papillomavirus sequences are not detectable by Southern blotting or general primer-mediated polymerase chain reaction in transitional cell tumours of the bladder

Summary A large series of transitional cell tumours has been screened for the presence of human papillomavirus (HPV) sequences using Southern blotting and general primer-mediated polymerase chain reaction (GP-PCR). The latter technique allows the detection of a broad spectrum of both sequenced and unsequenced HPV types using two primer pairs located in the highly conserved L1 and E1 regions of the HPV genome. No evidence for HPV infection was found in 100 transitional cell tumours, 6 cases of carcinoma in situ, 2 adenocarcinomas and a squamous carcinoma of the bladder and 3 cases of cystitis. Similarly, 12 bladder tumour cell lines were HPV-negative in these assays. Cervical carcinoma cell lines containing from 1–3 to 600 copies of the HPV genome were used as positive controls and were scored positive in all assays by both Southern blotting and GP-PCR. It is concluded that despite the close proximity of the urothelium to the genital mucosa and the resemblance of some bladder tumours to known HPV-induced lesions in other tissues, HPV infection is absent or very uncommon in bladder tumours.     

Evidence That Alpha-9 Human Papillomavirus Infections are a Major Etiologic Factor for Oropharyngeal Carcinoma in Black South Africans

Human papillomavirus (HPV) infection, most commonly genotype 16 of the alpha-9 family, is implicated in the etiology of a subset of oropharyngeal squamous cell carcinomas (OPSC) worldwide. Data are scarce regarding OPSC in South Africans, and three prior studies suggest no significant etiologic role for HPV. We aimed to investigate for evidence of HPV etiology in OPSCs from black South Africans by polymerase chain reaction (PCR) methodologies with determination of HPV subtype by sequencing, in situ hybridization (ISH), and p16^INK4a immunohistochemistry (IHC), as a surrogate marker for an HPV-driven tumor. It was hypothesized that HPV-driven tumors would be positive by PCR plus IHC and/or ISH whereas OPSCs with HPV background infections (HPV-passenger) would be positive by PCR alone. Formalin-fixed, paraffin-embedded tissues from 51 OPSCs collected between 2005 and 2010 from 41 patients were analyzed for HPV by GP5+6+ PCR (targeting the HPV L1 region), pU-1M/pU-2R PCR (targeting the HPV E6/E7 region) and HPV-31 specific PCR (targeting the E5 region), chromogenic ISH, and p16^INK4a IHC. All cases positive by PCR were subject to sequencing to determine HPV genotype. The patient mean age was 58.0 years and 88 % were male. Of the 51 evaluable tumors, 48 (94.1 %) were positive for HPV DNA by PCR: 25 (49.1 %) met criteria for an HPV-driven tumor, 23 (45.1 %) for HPV-passenger, and 3 (5.9 %) were HPV-unrelated. Sequencing of the PCR-positive cases revealed the following genotypes: combined HPV-16 and 31 (41.7 %), HPV-31 (25.0 %), HPV-16 (22.9 %), combined HPV-16 and 18 (6.3 %), and a single case each of HPV 18 and HPV 33. Studies via ISH were negative in all cases. In accordance with worldwide trends but contrary to prior South African data, HPV likely plays an etiologic role in a significant subset (at least 49.1 %) of OPSC in black South Africans. We found that the alpha-9 HPV family, particularly HPV-16 and 31 either in combination or separately, to predominate in our sample tumors. The use of multiple PCR primers increased sensitivity of viral detection, and a HPV-31 specific primer confirmed the presence of this genotype in many samples. Further studies including HPV E6/E7 mRNA assays are needed to better elucidate the pathogenic role of HPV in black South African OPSCs.     

In Situ Hybridization Signal Patterns in Recurrent Laryngeal Squamous Papillomas Indicate that HPV Integration Occurs at an Early Stage

Laryngeal papillomas are benign tumors that frequently recur and can compromise airways. We investigated HPV genotype, physical status, and protein expression in juveniles versus adults. Thirty-five laryngeal papilloma specimens were obtained from ten juveniles (1–16 years) and eleven adults (24–67 years). In cases of recurrent papillomatosis (7 juveniles, 7 adults), the first and last papillomas were assayed. HPV type was determined by GP5+/6+ PCR and dot blot hybridization. In situ hybridization (ISH) was performed on 34 specimens; the data were recorded in terms of diffuse (episomal HPV) and punctate (integrated HPV) signal patterns. Immunohistochemistry for the HPV L1 capsid protein, a marker of HPV productive status, was performed on 32 samples. All samples tested HPV positive: HPV 11 in 2/10 (20.0%) juveniles and 5/11 (45.5%) adults; HPV 6 in 7/10 (70%) juveniles and 5/11 (45.5%) adults; and HPV 6/11 double infection was noted in one juvenile and one adult. ISH signals (punctate ± diffuse) were detected among 7/10 (70.0%) juveniles and 7/11 (63.6%) adults. L1 staining was detected in 1/9 (11.1%) juveniles and 6/10 (60.0%) adults (P = 0.06). These data support the idea that integration of low-risk HPV types into the cell genome is an early and common event in the etiology of juvenile and adult recurrent laryngeal papillomas. Productive HPV infections may be more common in adults; accordingly, constant laryngeal re-infection by HPV shed from a productive lesion may contribute to adult recurrent lesions, whereas the mechanism of papilloma recurrence in juveniles may be more attributable to HPV integration.     

Laryngeal Squamous Cell Carcinoma in a 13 Year-Old Child Associated with Human Papillomaviruses 16 and 18: A Case Report and Review of the Literature

Squamous cell carcinoma (SCC) of the larynx is extremely rare in adolescents and typically has an aggressive nature. The mechanism of laryngeal oncogenesis is complex and little is known about the role that human papillomavirus (HPV) plays in SCC in adolescents. We report a case of invasive laryngeal SCC that co-expressed HPV DNA subtypes 16 and 18 in a 13 year-old boy. Detection of HPV DNA types 6, 11, 16, 18, 31, 33, and 51 was performed by in situ hybridization, with confirmation by polymerase chain reaction. Immunohistochemical staining with p16 and HPV 16/18 revealed diffusely positive staining in the tumor cells. Coinfection by HPV DNA types 16 and 18 has not been previously reported, but our case suggests that HPV is a risk factor in developing laryngeal SCC in children and adolescents. Future studies evaluating HPV in the pathogenesis of these lesions is recommended to determine its prognostic significance.     

In situ hybridization study of human papillomavirus from the penile cancer

The histochemical detection of human papillomavirus (HPV) was performed using the technique of in situ hybridization from the formalin fixed paraffin embedded specimens of penile carcinoma and condylomata+ acuminata . One of 19 penile cancer cases (5.3%) revealed the positive staining on the nuclei of the tumors for HPV type 16/18. However, the positive nuclei were scattered and localized in small part of the tumor which showed no koilocytosis. On the contrary, 11 of 12 condyloma acuminata cases (91.7%) showed positive staining on the nuclei of the tumors for HPV type 6/11, also 5 of the 11 cases (45.5%) revealed cross reaction for other type of HPV. The HPV types 6/11, 16/18 and 31/33/35 may be unrelated to the pathogenesis of the Japanese penile carcinoma. However, further study is necessary to evaluate that the number of HPV-DNA copy in our cases is too small, or the other type of HPV is responsibility.     

Presence of human papillomavirus DNA and abnormal p53 protein accumulation in lung carcinoma.

BACKGROUND: In some carcinomas inactivation of the tumour suppressor gene product p53, either by point mutation or indirectly by the human papillomavirus (HPV), has been suggested as two alternative routes to malignant transformation. To test this hypothesis in lung tumours, 43 lung carcinomas were analysed by in situ hybridisation and polymerase chain reaction (PCR) for the presence of HPV DNA, and the results were compared with p53 protein immunohistochemical analysis. METHODS: The presence of HPV DNA in lung carcinoma was detected by nucleic acid in situ hybridisation for HPV types 6, 11, 16, 18, 31, and 33 using nonradioactively labelled DNA probes. Polymerase chain reaction (PCR) analysis was performed on all cases showing positive HPV DNA labelling by in situ hybridisation and in an additional 13 negative cases. Abnormal nuclear accumulation of the p53 protein was revealed by immunohistochemistry using the avidin-biotin-peroxidase complex method and a CM-1 polyclonal anti-human p53 antibody and a monoclonal mutation-specific Pab 240 p53 antibody. RESULTS: HPV DNA was found by in situ hybridisation in 13 lung carcinomas (30%). In all these cases subtype-specific HPV DNA could also be detected by PCR. Abnormal p53 protein accumulation was seen in 21 of the 43 carcinomas (49%), of which 18 were HPV negative. Twelve (57%) of the CM-1 positive cases were also positive for the mutation-specific antibody Pab 240. There was an obvious inverse relationship between the presence of papilloma viral DNA and abnormal p53 protein accumulation. CONCLUSIONS: p53 plays an important part in the development of lung carcinomas and, in some cases, HPV may contribute to it by binding and inactivating the p53 protein.     

Human papillomavirus DNA sequences in cell lines derived from head and neck squamous cell carcinomas.

There is increasing evidence that human papillomaviruses (HPV) have a casual role in some neoplasms in human beings. As examples, DNA of HPV types 16, 18, and 31 are frequently present in genital cancers in humans. Recently, oncogenic HPV types have also been identified in neoplasms of the head and neck, including verrucous carcinoma of the larynx, squamous cell carcinomas of the oral cavity and larynx, and inverted papillomas of the nose. These findings and our resource of an extensive panel of head and neck squamous cell carcinoma (HNSCC) cell lines led us to begin to investigate how frequently HPV DNA was present in these tumor cell lines. For initial analysis, twenty-two HNSCC cell lines derived from 20 patients' tumors were selected as representative of our tumor cell line panel with respect to diversity of primary site, tumor stage, patient age, sex, and clinical course. For Southern analysis, cell line DNA was tested for hybridization with DNA probes for HPV types 6, 11, 16, 18, and 31. Polymerase chain reaction (PCR) analysis was also performed on five tumor cell lines using types 6, 11, 16, 18, and 52 as probes. Southern blot analysis revealed HPV-specific signals in two of the 22 HNSCC cell lines tested. One of these, UM-SCC-23, was HPV 31 positive, which to our knowledge is the first identification of HPV 31 in HNSCC. UM-SCC-63, the other HPV-positive tumor identified by Southern analysis, hybridized with both type 18 and 31. Of the five tumor cell lines tested with PCR, two were HPV positive.(ABSTRACT TRUNCATED AT 250 WORDS)     

Continuity of human papillomavirus (HPV) type between neoplastic precursors and invasive cervical carcinoma. An in situ hybridization study

Infection by the human papillomaviruses (HPV) represents an important risk factor in squamous lesions of various sites. More recently, data suggest that the glandular components of some tumors may also contain human papillomaviruses. This association may implicate HPVs in the genesis of these lesions as well. We present a longitudinal in situ hybridization study of HPV expression within a single patient, showing viral mRNA in squamous dysplasia, squamous and adenocarcinoma in situ, and in invasive adenosquamous carcinoma. There was continuity of the viral type (HPV 16) in the preinvasive and invasive portions of the lesions, and HPV mRNA was clearly demonstrable in the glandular components. The case illustrates the utility of in situ hybridization for the microscopic localization of viral gene expression, in addition to providing information about the viral type and perhaps the biologic potential of the lesion.     

乳腺癌HPV感染与临床病理学探讨

目的探讨乳腺癌及乳腺良性病变中人乳头状瘤病毒(HPV)感染的差异;HPV感染与乳腺癌病理类型的关系及对乳腺癌细胞形态产生的影响。方法在116例乳腺标本中,计进展期乳腺癌73例,乳腺良性病变43例。用显微镜观察浸润性导管癌细胞核异形性分级(nucleargrading,NG)、病毒感染相关的细胞内包涵体(inclusionbody)和“凹空细胞”(koilocytosis)样改变;以原位杂交法检测病变组织的HPVDNA。结果在73例乳腺癌中,29例(39.73%)HPV原位杂交检测呈阳性,43例乳腺良性病变中仅1例(2.33%)纤维腺瘤的部分上皮细胞呈HPV阳性。乳腺癌组HPV感染率明显高于乳腺良性病变组(P<0.001);HPV阳性病例集中在恶性程度较高的化生性癌和NG3、NG2组中(P<0.001)。73例乳腺癌中有21例(28.77%)可见癌细胞核内或核旁胞浆内包涵体,13例(17.81%)癌灶内见“凹空细胞”样改变。于有包涵体或“凹空细胞”样改变的乳腺癌病例,HPV阳性率分别超过70%和80%。结论部分乳腺癌及少数乳腺良性病变组织内存在HPV病毒感染。HPV阳性的乳腺癌恶性程度较高,临床上应密切随访。包涵体和“凹空细胞”样改变可在部分乳腺癌中出现,但出现率不高,然而原位杂交显示上述改变与HPV感染密切相关。     

Human papillomavirus-associated early vulvar neoplasia investigated by in situ hybridization

Of 21 consecutive cases of early vulvar neoplasia studied at the Istituto Nazionale Tumori of Milan, 62% appeared to be related to papillomavirus infection. This conclusion is the result of the present study by in situ hybridization with DNA probes of human papillomavirus (HPV) 6/11, 16, and 18 and of previous ultrastructural and immunohistochemical investigations. The proportion of cases associated with HPV was 78.5% for those (11/14) with histologic evidence of viral infection and 33% for those without (2/6). HPV 16 was detected in all cases that were positive by in situ hybridization except for one, which showed HPV 6/11 DNA. In one case there was a mixed triple infection for HPV 6/11, 16, and 18. The patient who was positive for HPV 6/11 had a giant condyloma associated with an inguinal lymph node containing a metastatic well-differentiated squamous cell carcinoma. Three cases were positive for papillomavirus internal capsid species-nonspecific antigen (PV-Ag) (with ultrastructural evidence of virions in one of them) and were negative for HPV-DNA hybridization. They appeared to be infected with a type of HPV not identified by the available probes. Three cases, and two sites of two other cases with double infection, were HPV-DNA-positive and PV-Ag-negative. They illustrate the limitation of immunohistochemical investigation in cases with high-grade intraepithelial neoplasia. Six cases of verrucous carcinoma of the vulva were negative for HPV DNA by in situ hybridization.     

Verruca vulgaris of the vulva in children and adults: a nonvenereal type of vulvar wart

Condyloma acuminata are common lesions of the vulva in adults, and associated with infection by human papillomavirus (HPV) types 6 and 11, which are acquired via sexual contact. The detection of an HPV 6/11 condyloma in the genital tract of a child, therefore, raises the question of sexual abuse. In this study, 29 genital warts in girls less than 5 years of age were examined for nongenital and genital tract HPVs by in situ hybridization. These results were compared with 275 vulvar lesions clinically suspicious for condyloma from adults. Of the 27 HPV-related lesions in young girls, 11 (41%) were due to HPV 2 whereas the other 16 (59%) were associated with HPV 6/11 infection. Of the 214/275 (78%) HPV positive vulvar lesions in adults, 6 (3%) were due to HPV 2 whereas 202/214 (94%) contained HPVs 6/11; 1 lesion contained HPV 16 and the 5 other lesions contained HPV 42, 43, or 44. Histologic correlation documented that the vulvar lesions positive for HPV 2 commonly showed the marked hyperkeratosis typical of verruca vulgaris. However, the verrucous pattern was present in lesions HPV 6/11 positive. It is concluded that verruca vulgaris of the vulva, which is likely not transmitted sexually, can occur, albeit rarely, in the genital tract of women and is common in the genital tracts of young girls. This highlights the value of HPV testing in such cases, especially if the histologic changes are consistent with verruca vulgaris.