Human papillomavirus types in anogenital warts of children

Tissue from anogenital warts of 25 children, 10 of whom were suspected of being victims of sexual abuse, was investigated by dot blot and Southern blot techniques for human papillomavirus (HPV) types. HPV DNA was detected in 22 children, two of whom had double infections. The genital HPV types 6 and/or 11 were detected in 20 children, and in three children other HPV types were found. One had HPV 18 (as well as 11); in a second child a possible skin type, HPV 2, was detected; and the third child was infected with an unidentified type. In three cases genital wart material was available from one of the parents, and in all three the HPV type was the same as that of the child. For nine other children one or both parents were reported to have genital warts. The source of infection appeared to be the adult genital tract, but sexual contact might not be the only means of transmission.     

生殖器疣活检标本中HPV多重检测技术的建立

目的探索生殖器疣活检标本中人乳头瘤病毒（HPV）的多重检测分型技术,为我国生殖器疣感染HPV的检测和分型研究的开展提供有效手段。方法针对病毒L1区基因序列自行设计通用引物MY09、MY11、GP5＋和GP6＋,并对反应条件进行优化,建立基于聚合酶链式反应（PCR）及序列分析的检测生殖器疣活检标本中HPV感染型别的方法。结果采用巢氏PCR方法能够特异扩出140bp的目的条带,实现HPV感染的定性检测;通过对目的基因片段的测序分析能够实现单型别感染/多型别复合感染HPV的分型和鉴定,并可以检测到HPV少见的特殊类型,同时也能提供已知的HPV型别的突变信息。结论基于HPV病毒L1区基因序列建立的PCR和序列分析检测技术是快速检测和分型生殖器疣活检标本中HPV的一种有效方法。     

Detection of Multiple Human Papillomavirus Types in Condylomata Acuminata Lesions from Otherwise Healthy and Immunosuppressed Patients

Condylomata acuminata, or genital warts, are proliferative lesions of genital epithelium caused by human papillomavirus (HPV) infection. HPV types 6 and 11 are most often detected in these lesions. Genital lesions consistent with exophytic condylomata acuminata were removed by excision biopsy from 65 patients, 41 of whom were otherwise healthy individuals (control group) and 24 of whom had conditions known to cause immunosuppression. Histologically, the majority of the lesions were typical condylomata acuminata. Three lesions removed from immunosuppressed individuals also contained foci of moderate to severe dysplasia (intraepithelial neoplasia grade II/III). A recently developed PCR and reverse blot strip assay was used to determine the specific HPV types present in the genital lesions. With a set of oligonucleotide primers based on the same primer binding regions used for the MY09 and MY11 primer pair, this PCR assay detects the presence of 27 HPV types known to infect the genital tract. All but two condylomata acuminata contained either HPV type 6 or 11. The predominant type in the lesions from control patients was HPV 6, while lesions from immunosuppressed types most often contained HPV 11. Condylomata acuminata from immunosuppressed patients contained significantly more overall HPV types than lesions from the control group. HPV types associated with an increased risk of dysplasia (high-risk types) were detected in 42 (64.6%) of the total of 65 specimens; 18 (43.9%) specimens were detected in the 41 otherwise healthy individuals, and 24 (100%) specimens were detected in the 24 immunosuppressed patients. HPV 16 was the most common high-risk type detected, found in 21 of 65 (32.3%) specimens. After HPV types 6 and 11, HPV types 53 and 54 were the most frequently detected low-risk HPV types. This study demonstrates that a high percentage of condylomata acuminata lesions contain multiple HPV types, including types associated with a high risk of dysplastic abnormalities. Further studies are needed to determine the influence these additional HPV types have on the epidemiology of genital tract HPV infections and the natural history of condylomata acuminata, especially in immunosuppressed patients.     

Dermatologic manifestations of HPV in HIV-infected individuals

Dermatologic human papillomavirus (HPV) infection in HIV patients manifests as both anogenital and nongenital skin disease. Anogenital HPV-related disease includes benign condyloma acuminata, the most common cutaneous manifestation of genital HPV infection; intermediate malignancy or premalignant conditions including giant condyloma acuminata (also called Buschke-Loewenstein tumor), anal intraepithelial neoplasia, penile intraepithelial neoplasia, and vaginal or vulvar intraepithelial neoplasia; and frankly malignant disease including Bowen’s disease and invasive anal, penile, or vulvar carcinoma. Cutaneous HPV-related disease in nongenital skin is also increased in HIV-positive patients, in the form of benign common warts, epidermodysplasia verruciformis-like skin lesions, and nonmelanoma skin cancers. This review and update addresses the above listed dermatologic manifestations of HPV disease in HIV-infected individuals, with an emphasis on new findings and published data from 2006 to 2008.     

Survey of histologic specimens of human cancer for human papillomavirus types 6/11/16/18 by filter in situ hybridization

Histologic specimens (317) of genital and nongenital cancers and normal tissue were analyzed for the presence of the DNA of human papillomavirus (HPV) 6, 11, 16, and 18 by filter in situ hybridization performed on paraffin-embedded, formalin-fixed tissue (HISTOFISH). HPV DNA was found in 73 of 172 (42%) anogenital lesions and 17 of 116 (15%) nonanogenital carcinomas. No HPV DNA was found in normal mouse skin (five samples), human autopsy liver (two samples), or kidney (eight samples), or in carcinomas of the breast (three samples), bladder (five samples), or colon (nine samples). Of the nongenital tumors, HPV DNA was found in the carcinomas of the lung (2 of 5), anus (7 of 18), esophagus (9 of 39), buccal cavity (1 of 5), and larynx (5 of 50). HPV DNA was also detected in 2 of 11 histologically normal specimens of the cervix and 1 of 3 human skin lesions. The detection of HPV DNA in carcinomas of the lung, larynx, and esophagus as well as in the anogenital region confirms recent suggestions that HPV types 6, 11, 16, and 18 have a wider association with different types of cancer than previously believed. The study also shows that HISTOFISH is a useful method for detecting HPV-DNA in histologic specimens.     

Human papillomavirus DNA determination of anal condylomata, dysplasias, and squamous carcinomas with in situ hybridization

Infection with types 6, 11, 16, and 18 of the human papillomavirus (HPV) is associated with condylomatous, dysplastic, or carcinomatous changes in the genital tract. Emerging evidence suggests that a similar series of lesions develops in the anal canal after exposure to the same HPV types. In situ hybridization was performed with the use of biotinylated DNA probes to HPV 6, 11, 16, and 18, so as to determine the frequency of HPV DNA in 45 perianal and/or anal condylomata, 6 anal intraepithelial neoplasias, and 13 anal squamous cell carcinomas. Of the 33 perianal and/or anal condylomata in which HPV DNA was detected, 13 contained HPV 6 and 11, 12 HPV 6, 7 HPV 11, and 1 HPV 6, 11, and 18. Two of four severe anal dysplasias contained HPV 16, whereas one case each of mild and moderate anal dysplasia contained HPV 6. No HPV DNA was detected in the anal squamous cell carcinomas. The study demonstrated the presence of HPV DNA in 73% of condylomata and 67% of anal dysplasias. The observations suggest that the cloacogenically derived anal epithelium is susceptible to infection by the same HPV types as infect the similarly derived epithelium of the lower female genital tract and that these HPV types result in some similar lesions, i.e., condylomata and dysplasias in both sites. A role in the genesis of anal cancer was not found in this study.     

Detection of human papillomavirus types 6, 11, 16 and 18 in mucosal and cutaneous lesions by the multiplex polymerase chain reaction.

A multiplex polymerase chain reaction (PCR) based on the simultaneous amplification of human papillomavirus (HPV) types 6/11, 16 and 18 in a single-step procedure was developed, using primers chosen in the E6-E7 region. The specificity and sensitivity of this technique have been proved by amplifying mixtures or various amounts of plasmid-containing HPV DNA; it allowed the detection of as few as 5-25 HPV DNA copies. Application of the multiplex PCR to 71 clinical samples showed that HPV DNA was detected in 80% (45/57 cases) of mucosal biopsies and 35% (5/14 cases) of cutaneous specimens. HPV 16 was predominant in high-grade CIN whereas HPV 6 and 11 were detected more frequently in genital condylomas and laryngeal papillomas. In cutaneous Bowen's disease HPV 16, 18 or 6/11 + 16 were detected and in squamous cell carcinomas HPV 6/11 or 16 were found. After sequence amplification with primers of one HPV type, the clinical samples displayed the same HPV types but the frequency of positive and coinfected lesions increased. Thus, multiplex PCR is a valuable technique for typing HPV DNA but coinfections may be underestimated.     

Overexpression of the proto-oncogene C-jun in association with low-risk type specific human papillomavirus infection in condyloma acuminata

Infection with different types of human papillomavirus (HPV) is associated with neoplasia at different anatomic sites. The “low-risk” HPVs (LR-HPV) are responsible for benign genital lesions such as condyloma acuminata. In order to clarify the tumorigenic mechanism of LR-HPV, the HPV infection status was investigated and the expression of the c-jun proto-oncogene in different HPV-related skin and genital lesions analyzed. Of the 17 condyloma specimens analyzed by Western blotting, 13 cases (76.5%) exhibited overexpression of the c-jun gene. All 13 cases harbored high copy numbers of the LR-HPV genome with an average of 926 copies per cell, whereas the other four cases had an average of 12 copies of LR-HPV per cell (P < 0.001). Further typing of HPV by Southern blotting revealed that HPV-6 and HPV-11 infections predominated in c-jun positive cases. The c-jun protein was detected much less frequently in cervical cancers (three of 29, or 10.3%) and skin warts (one of 10), and was not detected in five genital polyps or in five normal cervical tissues. These findings suggest a type 6/11-specific induction of c-jun gene expression in HPV-related neoplastic lesions. © 1996 Wiley-Liss, Inc.     

Detection of Human Papillomavirus Types 6 and 11 in Pubic and Perianal Hair from Patients with Genital Warts

Genital human papillomavirus (HPV) types 6 and 11 are of clinical importance due to their role in the development of anogenital warts. A pilot study was performed to investigate whether DNAs from HPV types 6 and 11 are present in hairs plucked from the pubic and perianal regions and eyebrows of patients with genital warts at present and patients with a recent history of genital warts. Genital HPV DNA was detected in 9 of 25 (36%) pubic hair samples and in 11 of 22 (50%) perianal hair samples by the CPI/CPIIg PCR. After sequencing of 17 of 20 samples, HPV type 6 or 11 was detected in 6 of 25 (24%) hair samples from the pubis and 8 of 22 (36%) hair samples from the perianal region. These types were not detected in plucked eyebrow hairs. In contrast, the HPV types associated with epidermodysplasia verruciformis were detected in similar proportions (62%) in both samples of pubic and eyebrow hairs. Moreover, HPV type 6 and 11 DNAs were detected in pubic hairs plucked from two patients who had been successfully treated and who did not show any lesion at the time of hair collection; this finding is an argument that HPV DNA may persist in this region. The presence of genital HPV types in plucked pubic and perianal hair suggests that there is an endogenous reservoir for HPV which may play a role in the recurrences of genital warts.     

Degenerate and Nested PCR: a Highly Sensitive and Specific Method for Detection of Human Papillomavirus Infection in Cutaneous Warts

The role of human papillomavirus (HPV) in anogenital carcinogenesis is firmly established, but evidence that supports a similar role in skin remains speculative. Immunosuppressed renal transplant recipients have an increased incidence of viral warts and nonmelanoma skin cancer, and the presence of HPV DNA in these lesions, especially types associated with the condition epidermodysplasia verruciformis (EV), has led to suggestions that HPV may play a pathogenic role. However, differences in the specificities and sensitivities of techniques used to detect HPV in skin have led to wide discrepancies in the spectrum of HPV types reported. We describe a degenerate nested PCR technique with the capacity to detect a broad spectrum of cutaneous, mucosal, and EV HPV types. In a series of 51 warts from 23 renal transplant recipients, this method detected HPV DNA in all lesions, representing a significant improvement over many previously published studies. Cutaneous types were found in 84.3% of warts and EV types were found in 80.4% of warts, whereas mucosal types were detected in 27.4% of warts. In addition, the method allowed codetection of two or more distinct HPV types in 94.1% of lesions. In contrast, single HPV types were detected in all but 1 of 20 warts from 15 immunocompetent individuals. In summary, we have established a highly sensitive and comprehensive degenerate PCR methodology for detection and genotyping of HPV from the skin and have demonstrated a diverse spectrum of multiple HPV types in cutaneous warts from transplant recipients. Studies designed to assess the significance of these findings to cutaneous carcinogenesis are under way.     

Distribution of human papillomavirus types in the anogenital tract of females and males

Human papillomavirus (HPV) infection is the most common sexually transmitted infection in both men and women, but there are limited data comparing the prevalence of HPV infection between genders and in different anogenital sites. This cross‐sectional analysis describes the distribution of HPV types in the genital tract of 3,410 consecutive females and 1,033 males undergoing voluntary screening for HPV and referred to a single institution. The relationship between specific HPV types and the presence of anogenital lesions was examined. In both females and males, the overall prevalence of HPV infection was about 40%. A wide variety of HPV types was identified, but the prevalence of different types was remarkably similar in the two genders, even when considering different anatomical sites. HPV‐6 was the most frequent (prevalence 13%) type in all anogenital sites in men followed by HPV‐16 (7%), while HPV‐16 was the most common type in women (about 6%), either in the cervix, vagina, or vulva, followed by HPV‐6. In addition to HPV‐16, HPV‐58, HPV‐33, HPV‐31, and HPV‐56 were the carcinogenic types detected most commonly and were significantly associated with high‐grade squamous intraepithelial cervical lesions, while HPV‐53 and HPV‐66 were the most common among possibly carcinogenic types. In both genders, anogenital warts were associated with HPV‐6 and HPV‐11 infection, and, less frequently, with other types, like HPV‐54, HPV‐62, and HPV‐66. These results show that genital HPV infection involves numerous HPV types, which have similar distribution patterns in females and males and in different anogenital anatomical sites. J. Med. Virol. 82:1424–1430, 2010. © 2010 Wiley‐Liss, Inc.     

Anal cancer. Microscopic condyloma and tissue demonstration of human papillomavirus capsid antigen and viral DNA

Sixteen cases of squamous cell carcinoma of the anus, including 4 incidentally discovered in situ lesions, and 3 anal condylomas, were examined for the presence of human papillomavirus (HPV). All in situ tumors and 6 of the invasive tumors were associated with histologic changes typical of condyloma, despite the absence of clinical anogenital warts. Immunohistochemical studies for viral capsid antigen gave positive reactions in two anal warts and in the condylomatous area associated with one invasive tumor. In situ hybridization was accomplished using isotopic DNA probes for HPV 6/11, 16, 18, and 31. Human papillomavirus 6/11 was expressed in the corresponding capsid-positive regions in the two warts and the wart-associated invasive carcinoma. Both HPV 6/11 and HPV 16 were associated with one carcinoma in situ, and HPV 16 was also found within two invasive anal carcinomas, one of which was associated with an extensive vulvar cancer. While these observations do not resolve the "passenger" or direct oncogenic role for HPV in anal carcinoma, the circumstantial evidence is that the oncogenic influence is similar to that accepted for female genital tract cancer.     

Immunohistochemical detection of p53 protein in cutaneous lesions from transplant recipients harbouring human papillomavirus DNA

Human papillomaviruses (HPV) are thought to be involved in the malignant evolution of cutaneous lesions from transplant recipients. As E6 proteins from potentially oncogenic HPV types degradep53 tumour suppressor gene product in vitro, we analysed p53 protein status in benign, premalignant and malignant skin lesions from grafted patients, to determine whether HPV may interfere with p53 function. With immunohistochemistry, p53 protein accumulation was detected in 70% of skin lesions from grafted patients. p53 immunoreactivity was confined to basal keratinocytes in benign lesions (warts, condylomas), while suprabasal keratinocytes were also stained in premalignant and malignant skin lesions (precancerous keratoses, squamous cell carcinomas). Multiple HPV carriage was detected with in situ hybridization in benign and malignant skin lesions from transplant recipients: low risk HPV types 1, 2, 6, 11 and potentially oncogenic HPV types 5, 16, 18 were frequently found. There was no clear correlation between p53 detection and the presence of the HPV types under study. The frequent detection of p53 protein in cutaneous lesions from grafted patients is suggestive of p53 protein accumulation interfering with normal function. Our results may reflect the presence of mutated p53 proteins due to the mutagenic effect of ultra-violet (UV), or wild-type p53 protein accumulation in response to UV-induced DNA damage, or may be produced by the interaction with HPV-encoded E6 proteins.     

High-grade dysplasia in genital warts from two patients infected with the human immunodeficiency virus

Cancer-associated human papillomavirus (HPV) types are detected in genital warts removed from immunosuppressed individuals more commonly than from those occurring in otherwise healthy individuals. The prognosis of genital warts containing cancer-associated HPV types is not known. Because it is assumed that genital warts are benign lesions, they are usually treated by destructive therapies without prior knowledge of histopathology. The aim of the present study was to determine whether genital warts from individuals with or without human immunodeficiency virus (HIV) contain high-risk HPV types or areas of dysplasia. The study design was a nonrandomized analysis of genital warts removed by excision biopsy from 15 HIV-infected patients and 15 HIV-negative patients. The tissue was analyzed for HPV DNA by hybrid capture, and microscopic sections of each biopsy were examined for areas of dysplasia. Genital warts from HIV-infected patients contained cancer-associated (“high risk”) HPV types in 9 of 15 cases, including 1 that contained only a high-risk type. High-grade dysplastic abnormalities were present in 2 of the 15 lesions from this group, both of which contained high-risk HPV types. Four genital warts removed from HIV-negative patients contained high-risk HPV types, but none contained dysplastic abnormalities. It is concluded that genital warts from HIV-infected patients often contain high-risk HPV types. Such lesions may exhibit dysplastic changes. The frequency of dysplastic changes in genital warts from HIV-infected patients is not known. Biopsy of genital warts may be indicated prior to additional therapy in HIV-infected patients, and surgical removal should be considered as a preferred treatment option in these patients. J. Med. Virol. 54:69–73, 1998. © 1998 Wiley-Liss,Inc.     

Filaggrin expression in cutaneous and mucosal human papillomavirus induced lesions

A series of 32 human papillomavirus induced lesions derived from epidermis and mucosa was studied for the modulation of filaggrin-profilaggrin (F-PF) expression according to the degree of virus infection as compared to normal skin and mucosa biopsies. This investigation was carried out on frozen sections using indirect immunofluorescence for filaggrin detection and group specific viral antigen and by in situ hybridization with biotinylated probes for viral DNA detection and typing. The 9 cutaneous warts showed an increase of F-PF expression in upper layer cells as compared to normal epidermis, which could be related to the high production of virus (viral antigen and HPV types 1 or 2). The 5 condyloma acuminata displayed also an enhanced expression of these components which was located in several upper layers but virus infection was confirmed in 2 of them with HPV types 6, 11 or 16. The 6 laryngeal papillomas exhibited a granular reactivity pattern for F-PF in suprabasal cell layers with an increase in the upper layers; viral antigen was found in 4 cases and HPV DNA types 6, 11 or 16 were detected in 4 specimens. Conversely among 12 cervical intraepithelial neoplasia, F-PF was expressed only in very superficial layers in few cases, without any correlation with the DNA detection (6, 11 or 16, 18). Taken together these data are suggestive of an intense expression of F-PF in benign lesions which can replicate the virus and a discrete or an absent expression of these components in premalignant or malignant lesions.     

Human papillomavirus in exophytic condylomatous lesions on different female genital regions.

Clinically diagnosed exophytic condylomatous lesions on the vulva (20 cases), vagina (5 cases), and cervix (9 cases) were examined pathologically, and human papillomavirus (HPV) types present in those lesions were identified by Southern blot hybridization analysis. All vulvar and vaginal lesions showed typical histopathological features of classical condylomata, and HPV 6 and 11 were found in 15 vulvar and 3 vaginal lesions and in 5 vulvar and 2 vaginal lesions, respectively. In 5 cervical lesions with typical condylomatous changes, HPV 6 or 11 was also detected; however, HPV 16 was found in 2 cases of cervical lesion surrounded by prominent intraepithelial neoplasia, and HPV 31 was found in 2 cases of slightly elevated lesion with intraepithelial neoplasia. These observations suggest that HPV 6 and 11 have the potency to induce the specific pathological changes, condylomatous, in any regions of the female lower genital tract.     

Genital seborrheic keratoses are human papillomavirus-related lesions. A linear array genotyping test study

Controversy exists about the meaning of human papillomavirus (HPV) detection in seborrheic keratosis (SK). To clarify the pathogenic contributing role of HPV in the development of genital SK, we have studied 40 genital SKs, 20 extragenital SKs, and 20 non-SK genital lesions by polymerase chain reaction for HPV, using a Linear Array Genotyping test that detects 37 genital HPV types. Twenty-eight of the 40 genital SK specimens (70%) were positive for HPV. Twenty-seven of the 28 positive cases (96%) contained HPV6, one of them associated to HPV18 and HPV35 (4%), and the remaining lesion (4%) harbored HPV55. However, HPV was detected in only 2/20 extragenital SK samples (10%) and in 1/20 non-SK genital lesions (5%). Our results support a pathogenic relationship between HPV and genital SK by showing: 1) a high rate of virus detection in these lesions, with a strong predilection for HPV6, and 2) scarcity of genital HPV types in most of the remaining non-SK cutaneous genital lesions and in the extragenital SKs. HPV cannot be found in a minority of genital SKs using highly sensitive techniques, and therefore, other presently unknown factors may also be implied in the pathogenesis of these lesions.     

Immunophenotypic and viral (human papillomavirus) correlates of vulvar seborrheic keratosis

Human papillomavirus (HPV) infections of the genital mucosa classically present as warts (condylomata) and are traditionally defined by the presence of viral cytopathic effect (koilocytosis). In recent years, HPV has been detected in vulvar epithelial changes lacking koilocytosis, including squamous papillomas and lesions closely resembling seborrheic keratosis (SK). The purpose of this study was to determine the frequency and type of HPV associated with vulvar SK (VSK) and to compare expression of biomarkers (p16, Mib-1, and cyclin E) in these lesions. Sixty-seven biopsy specimens, including 25 VSKs, 10 nondiagnostic vulvar acanthoses, 12 fibroepithelial polyps (FEPs), and 20 nongenital cutaneous SKs (CSKs), were studied. Biopsy specimens were typed for HPV by polymerase chain reaction and immunostained with Mib-1, cyclin E, and p16(INK4) antibodies. Eighteen of 25 VSKs (72%), 0 of 10 nondiagnostic vulvar acanthuses (0%; P = 0.0001), 2 of 12 FEPs (16.7%; P = 0.004), and 3 of 20 CSKs (15%; P = 0.0002) scored HPV positive. Increased Mib-1 staining was significantly more common in VSKs than in other vulvar lesions, but not in CSKs; increased p16 and cyclin E staining was not more common. VSKs are morphologically and immunophenotypically similar to CSKs but distinct by their association with HPV. Unlike the cervix, p16 and cyclin E will not consistently distinguish VSKs from HPV-negative lesions due to underexpression in low-risk HPV infections (p16) and less-restricted expression in vulvar lesions (cyclin E). Whether CSKs are associated with other forms of HPV infection remains to be determined.     

Detection of human papillomavirus in skin and genital lesions of renal allograft recipients by in situ hybridization

Renal allograft recipients have an increased incidence of malignancy including squamous carcinoma of cervix and skin. There is growing evidence that human papillomavirus (HPV) has a part to play in malignant transformation at these sites. We have previously identified HPV DNA in the skin and genital lesions of such patients by dot and Southern blotting. In situ hybridization studies, using biotinylated DNA probes for HPV 4, 5 and 8 in skin lesions and 6, 11. 16 and 18 in genital lesions, were performed on tissues derived from the same group of patients. In the cutaneous lesions, only 25% of the specimens probed were found to contain virus by in situ hybridization; 60% of these specimens were found to harbour virus by dot and Southern blotting. In situ hybridization revealed HPV 16 and/or 18 in 86% of the genital lesions probed.     

Detection of capsid antigen of human papillomavirus (HPV) in benign lesions of female genital tract using anti-HPV monoclonal antibody.

We established a murine monoclonal antibody (K1H8) to human papillomavirus (HPV) using alkaline-disrupted virions of HPV type 1 (HPV-1) as the immunogen. K1H8 recognized a 57 kD capsid protein of HPV-1 and detected the antigen in paraffin sections of formalin-fixed tissue. With K1H8, we examined immunohistochemically 68 biopsy specimens obtained from the female genital tract. The specimens were histologically condyloma acuminatum or koilocytotic lesions with or without dysplasia and each specimen was found to harbour a single type of genital HPV, such as types 6, 11, 16, 18, 31, 33, 42, 51, 52, 56, and 58, by Southern blot hybridization analysis. The antigen was localized in the nuclei and occasionally in the cytoplasm of squamous cells showing koilocytotic changes. Eighty-four per cent of the specimens (57 cases) showed positivity for the antigen, indicating that K1H8 is a broadly-reactive antibody to various genital HPVs. The results suggest that benign mucosal lesions of the female genital tract are more frequently associated with viral production and are a potential source of transmission.