Cervical signs of HPV infection in PAP-smear negative women with external genital warts

Forty-eight women with external genital warts, all with normal cervical cytological PAP smears, were examined by means of colposcopy. One cervical biopsy for histological evaluation was taken from each woman, irrespective of the colposcopic findings. Koilocytosis was detected in 18/48 (38%) and dysplasia (CIN-1) in 3/48 (6%) of the patients. The presence of aceto-white lesions on the cervix was significantly associated with abnormal histology; 12 of 17 (71%) aceto-white lesions and 8 to 31 (26%) normal-appearing cervices showed histological changes indicating HPV infection (p less than 0.01). Women with koilocytosis and dysplasia had genital warts for a mean of 201 days compared with 79 days in women with normal cervical histology (p less than 0.01). It is concluded that even the clinically normal appearing cervix frequently is a reservoir for HPV and that colposcopy should be a routine procedure in women with external genital warts, irrespective of the result of the PAP smear, to provide a basis for proper counselling and individual therapy.     

Cervicovaginal involvement in pemphigus vulgaris: a clinical study of 77 cases

BACKGROUND: Pemphigus vulgaris (PV) is an autoimmune blistering disease which is known to involve the female genital tract, but the frequency at which this occurs is unknown. There are few reports in the literature of the cytological appearance of PV on cervicovaginal smears. OBJECTIVES: To evaluate involvement of the female genital tract and the appearance of cervicovaginal Papanicolaou (Pap) smears in PV. METHODS: The study included 77 patients with PV who attended between April 2005 and February 2007. Each patient was subjected to gynaecological examination and cervicovaginal Pap smear. RESULTS: Genital lesions were observed in 39 patients (51%). Of these, the labia minora were involved in 36 patients (92%), the labia majora in 11 (28%), the vagina in 14 (36%) and the cervix in six (15%). Cervicovaginal Pap smears of 20 of 77 patients (26%) showed PV. Of 72 satisfactory Pap smears, the cervical Pap smear was normal in 25 patients (35%), inflammatory in 43 patients (60%), and dysplastic (low-grade squamous intraepithelial neoplasia) in four patients (6%). CONCLUSIONS: Involvement of the female genital tract with PV might not be as infrequent as was previously thought; it is probably the second most common mucosal site of PV after the oral mucosa. Genital lesions may be missed and the need for thorough pelvic examination should not be overlooked.     

Detection of human papillomavirus DNA on the fingers of patients with genital warts

OBJECTIVE: To determine whether patients with genital warts carry human papillomavirus (HPV) DNA on their fingers. METHODS: 14 men and eight women with genital warts had cytobrush samples taken from genital lesions, finger tips, and tips of finger nails. Samples were examined for the presence of HPV DNA by the polymerase chain reaction. RESULTS: HPV DNA was detected in all female genital samples and in 13/14 male genital samples. HPV DNA was detected in the finger brush samples of three women and nine men. The same HPV type was identified in genital and hand samples in one woman and five men. CONCLUSION: This study has identified hand carriage of genital HPV types in patients with genital warts. Although sexual intercourse is considered the usual mode of transmitting genital HPV infection, our findings raise the possibility of transmission by finger-genital contact.     

Human papillomavirus DNA detection in primary anogenital warts and cervical low-grade intraepithelial neoplasias in adults by in situ hybridization.

In this study, 58 consecutive patients with primary anogenital warts were selected from patients attending a genitourinary clinic. Patients were grouped on the basis of clinical lesion site, i.e. patients with genital warts only, patients with perianal or anal canal warts only, and patients with concurrent perianal and genital warts. Of these patients, 38% of the men (12/31) and 33.3% of the women (9/27) had other anogenital infections, such as nonspecific urethritis (NSU) or nonspecific genital infection, which were the most common. Of the patients who had perianal warts, 37% of the men (7/19) and 25% of the women (4/16) also had warts in the anal canal. Of the women who had anogenital warts, 63% (17/27) had concurrent subclinical low-grade cervical intraepithelial neoplasia (CIN) lesions. Human papilloma virus (HPV) DNA (either 6 or 11, 16 or 18, or 31 or 33 or 35) was detected in 53.3% (40/75) of the anogenital wart biopsy samples, and in 35.2% (6/17) of the low-grade CIN lesions. HPV types 6 or 11 were the most common types in anogenital warts (45.3%); and in CIN lesions HPV types 6 or 11 and 16 or 18 were found with equal frequency (17.6% each). There were no significant differences in HPV types between patients with genital warts and patients with perianal and anal canal warts. Anogenital infection with HPV is multicentric; external anogenital warts and subclinical CIN lesions often exist concurrently. The low prevalence of HPV DNA detected in anogenital warts and CIN biopsy samples may be due to insensitivity of the in situ hybridization technique used in this study.     

Dual genitotropic human papillomavirus infections in genital warts.

BACKGROUND AND METHODS--We have carried out a prospective study of dual genitotropic human papillomavirus (HPV) infections by means of two different DNA detection methods in biopsy specimens obtained from patients who were examined for genital warts at the STD clinic of the School of Medicine in Seville, between January 1990 and December 1991. RESULTS--100 patients with a clinical diagnosis of condilomata acuminata were seen during the study period. DNA of the genitotropic HPV 6/11, 16/18 and 31/33/35 was detected by an in situ hybridisation method in 75 (77%) of the 98 evaluable samples; one of the genotypes tested in 59 (61%) samples, and two or more genotypes tested in the remaining 16 (15%) samples. In 21 (98%) of the 23 negative samples by in situ hybridisation, we were able to detect DNA of genital HPV using a polymerase chain reaction amplification method (PCR). Among the 34 samples where PCR was applied we confirmed the presence of two different HPV genotypes in eight samples. CONCLUSIONS--The frequency of dual infections with human genitotropic papillomavirus in genital warts was 8%, although we believe that this rate should be higher as we have not used the PCR method in all of the samples.     

Human papillomavirus: a review

Human papillomavirus infection remains a great source of morbidity and mortality. Progress in understanding the structure of HPV and its pathogenesis has led to a wide variety of possible new treatment modalities to combat HPV-related disease. Most HPV infections (whether high risk or low risk) resolve without any medical intervention. Persistent or progressive disease, however, remains difficult to treat. Although currently available therapies have proved efficacious and tolerable in the treatment of nongenital and genital warts, no single therapy is uniformly effective in eradicating persistent HPV infection. Cytodestructive methods, such as cryotherapy, remain the primary treatment modality for nongenital warts. Immune response modifiers, such as imiquimod, currently show the greatest promise in treating HPV-induced anogenital lesions, both with respect to complete response and in preventing recurrence. Human papillomavirus infection is one of the most common sexually transmitted diseases in the world, and cervical cancer still causes significant morbidity and mortality. Pap smear tests have greatly reduced the incidence and mortality of cervical cancer in developed countries. Additional research will focus on primary and secondary prevention strategies. Vaccines against high-risk HPV types are promising modalities currently under investigation to prevent HPV infections and possibly to treat them.     

Subclinical human papilloma virus infection in condylomata acuminata patients attending a VD clinic.

In 37 (77%) of 48 patients with external genital warts, application of 5% acetic acid revealed areas of acetowhite epithelium. The lesions were not clinically apparent before acetic acid was applied but were easily detected without the use of a colposcope. In a control group of 20 patients with chlamydial urethritis and no history of genital warts, none had acetowhite genital lesions. Histological examination of biopsy specimens from the flat acetowhite lesions showed HPV infection with koilocytosis in 29 (78%) and in 3 (8%) intra-epithelial neoplasia grade II-III. Using in situ hybridization with commercially available biotinylated DNA probes, HPV types 16/18 could be detected in 7 (24%) patients with koilocytosis and in 3 (100%) patients with dysplasia. Simultaneous infection with HPV types 6/11, 16/18, and 31/33/35 was found in 8 of the 13 HPV DNA-positive patients. It is concluded that subclinical HPV-induced acetowhite lesions are common among patients with genital warts and that these flat lesions may be associated with a high grade of dysplasia. Consequently, routine use of the acetic acid test on the genital epithelium is recommended in patients with condylomata acuminata in order to diagnose and treat all HPV-infected areas.     

Genital human papillomavirus infections in patients attending an inner-city STD clinic.

One hundred and sixteen consecutive women attending a Baltimore City STD clinic were studied for the prevalence of human papillomavirus (HPV) infection of the genital tract using three criteria: presence of clinically recognized (visible) genital warts, cytopathologic evidence suggestive of HPV infection in a Papanicolaou smear, and analysis of cervical scrapes for genital tract HPV genomic sequences by Southern hybridization. The women were young (median age: 22 years) and more than 80% had a history of one or more STDs. The prevalences were 17% for visible warts, 41% for cytologic findings suggestive of HPV infection, and 12% for HPV DNA in cervical scrapes. Comparing the results of the three techniques, HPV DNA was found significantly more often in cytopathology-positive women than in cytopathology-negative women (18% vs. 5%, P = 0.05) and in women with visible warts than in women without visible warts (29% vs. 6%, P = 0.01). Visible warts were more common in women with HPV-DNA-positive cervical scrapes than in HPV-negative women (50% vs. 14%, P = .01). Although 52% of women were judged as infected by at least one of the three criteria, only 4% were infected by using all three criteria. The prevalence of infection was 23% if cytopathology alone was excluded as evidence of HPV infection. These results indicate the difficulty in an accurate estimation of the prevalence of HPV infections, even in a high-risk population.     

Role of the Papanicolaou smear in diagnosis of chlamydial infections

The accuracy of the routine Papanicolaou (Pap) smear in diagnosis of Chlamydia trachomatis infection of the cervix has stimulated controversial reports over the years. In the present study Pap smears from 100 women, evenly divided between culture-positive and culture-negative for C. trachomatis, who had been seen in a single university clinic and cultured in the same laboratory were reviewed by two cytologists. With use of typical inclusions as evidence of chlamydial infection, the sensitivity of the Pap smear was 8.3%. Review of another series of 40 Pap smears that had been reported previously as positive for C. trachomatis showed only 25 with inclusions, an observation suggesting that routine Pap smears are being overread for chlamydial infection. Attempts to improve the sensitivity by immunoperoxidase staining were unsuccessful. Therefore, if strict cytologic criteria are used, C. trachomatis infections may be diagnosed on Pap smears, but the sensitivity will be low.     

Genital carriage of human papilloma virus (HPV) DNA in prepubertal girls with and without vulval disease

Human papilloma virus (HPV) can reach a child's anogenital area by vertical transmission or by close contact, which can be either sexual or nonsexual. Our objective was to compare HPV in prepubertal girls with and without lichen sclerosus (LS). We compared the frequencies and types of HPV in girls with LS with those in children with non-LS vulval disease (vulval swab and urine) and in children with no known vulval disease (urine only). HPV DNA was detected using a nested polymerase chain reaction (PCR) with general and consensus primers amplifying a region of the L1 gene, and PCR amplicons were typed using reverse hybridization with labeled HPV type-specific probes. Specimens untypeable by this method were typed by DNA sequencing. In the cohort of children with LS, we recorded the presence of maternal anogenital warts or a dysplastic cervical smear within 3 years of the affected child's birth. We found that HPV was present in the urine and vulval swabs of 8 of 32 children with LS and in 2 of 31 children with non-LS vulval disease, but also in the urine of 7 of 29 controls. In those with LS, the frequency was not increased significantly, but the types were predominantly those commonly associated with dysplasia of the cervix, penis, vulva, and anus, as opposed to the broader spectrum of types found in the control group, not all dysplasia associated. Two of the 32 mothers reported warts, and 15 of 32 (46.9%) had an abnormal smear. (The national average of abnormal cervical smears is less than 10%.) We concluded that HPV appears to be common in all prepubertal girls, but children with LS carried types associated with dysplasia and their mothers had had a high incidence of dyskaryotic smears.     

Sexual behaviour of women with human papillomavirus (HPV) lesions of the uterine cervix.

To analyse the epidemiological aspects contributing to the transmission of human papillomavirus (HPV) lesions (flat, inverted, and papillomatous condylomas) of the uterine cervix, we recorded the sexual behaviour of 146 women who consecutively attended the department of obstetrics and gynaecology of Kuopio University Central Hospital with a cervical HPV lesion (with or without concomitant cervical intraepithelial neoplasia (CIN]. Similar data were collected from an age matched group of women with no signs of gynaecological infection. The sexual habits of the women infected with HPV differed from those of healthy controls in most aspects studied, including an earlier onset of sexual activity (p less than 0.05), lower number of deliveries (p less than 0.05), less regular use of contraceptive measures (p less than 0.05), and use of the condom instead of intrauterine contraceptive device (IUCD) (p less than 0.0001). They also differed from controls in giving histories of more frequent episodes of: CIN (p less than 0.005), abnormal Pap (Papanicolaou) smears (p less than 0.0001), sexually transmitted disease (STD) (p less than 0.05), and genital warts (p less than 0.001). Furthermore, they had more multiple sexual partnerships (both past and current) than the controls (p less than 0.0001 and 0.005 respectively), they had not established permanent partnerships as often as the controls (p less than 0.001), and they had a higher frequency of casual relationships (p less than 0.0001). In addition, their own and their partners' sexual hygiene was poorer than in the control subjects (p less than 0.05 and 0.001 respectively). The results show the dramatic influence of sexual behaviour on the transmission of cervical HPV lesions, which are known to be intimately associated with CIN in many cases.     

Sexual behaviour of women with human papillomavirus (HPV) lesions of the uterine cervix

To analyse the epidemiological aspects contributing to the transmission of human papillomavirus (HPV) lesions (flat, inverted, and papillomatous condylomas) of the uterine cervix, we recorded the sexual behaviour of 146 women who consecutively attended the department of obstetrics and gynaecology of Kuopio University Central Hospital with a cervical HPV lesion (with or without concomitant cervical intraepithelial neoplasia (CIN]. Similar data were collected from an age matched group of women with no signs of gynaecological infection. The sexual habits of the women infected with HPV differed from those of healthy controls in most aspects studied, including an earlier onset of sexual activity (p less than 0.05), lower number of deliveries (p less than 0.05), less regular use of contraceptive measures (p less than 0.05), and use of the condom instead of intrauterine contraceptive device (IUCD) (p less than 0.0001). They also differed from controls in giving histories of more frequent episodes of: CIN (p less than 0.005), abnormal Pap (Papanicolaou) smears (p less than 0.0001), sexually transmitted disease (STD) (p less than 0.05), and genital warts (p less than 0.001). Furthermore, they had more multiple sexual partnerships (both past and current) than the controls (p less than 0.0001 and 0.005 respectively), they had not established permanent partnerships as often as the controls (p less than 0.001), and they had a higher frequency of casual relationships (p less than 0.0001). In addition, their own and their partners' sexual hygiene was poorer than in the control subjects (p less than 0.05 and 0.001 respectively). The results show the dramatic influence of sexual behaviour on the transmission of cervical HPV lesions, which are known to be intimately associated with CIN in many cases.     

Urogenital and anal papillomavirus infections

Recently virologists and clinicians have focused attention on infections with human papillomaviruses (HPV). This is due to the ubiquity, the increasing frequency and the possible association of these viruses with the development of squamous cell carcinomas of the skin and of the mucous membranes of the respiratory, gastrointestinal, genitourinary and anorectal tracts. HPV represent a very heterogeneous group of DNA tumor viruses. By means of molecular-biological techniques, more than 40 HPV types have been recognized. In the urogenital and anal tract, papillomaviruses have been associated with venereal warts (condylomata acuminata), which have been known and recognized as a sexually transmitted disease since the Romans. Furthermore, an association has been made recently between HPV and nonpapillomatous, sometimes macular lesions: flat condylomata of the uterine cervix and of the vagina, flat condylomatous lesions and pigmented papules. The latter are localized at the mucocutaneous borders and at the skin of the lower genital tract and of the perianal and crural region. Like epidermodysplasia verruciformis, only some virus types (HPV 16, HPV 18) are regularly found in malignant, invasive squamous cell carcinomas of the genital tract, whereas others (HPV 6, HPV 11, HPV 2, HPV 10, HPV 31) are associated preferentially with benign papillomas and dysplasias. In view of the different possible oncogenic potential of the individual genotypes, early determination of the virus type probably has not only diagnostic but also prognostic value. As HPV 16 DNA is regularly present in bowenoid papulosis (flat condylomatous lesions and pigmented papules of the male genital tract), a natural reservoir has been found from which these viruses could be transmitted to the sexual partner. Knowledge of the HPV-associated clinical pictures is therefore the prerequisite for diagnosis and treatment of both the patient and his sexual partner. Clinical observation, cytology and virus typing from genital smears of both partners represent preventive methods that may contribute to the early detection of genital cancer.     

Anal intercourse: a risk factor for anal papillomavirus infection in women?

OBJECTIVE--To determine whether anal intercourse is a risk factor for anal HPV infection in women. DESIGN--Results derived from clinical examination, anal cytology and HPV DNA hybridisation were correlated with data obtained from a questionnaire administered to the patients at the time of their clinical examination. SETTING--A sexually transmitted diseases (STD) clinic in Sydney, Australia. SUBJECTS--31 women attending the clinic for HPV related problems. METHODS AND RESULTS--A thorough history was elicited from each woman followed by physical examination of the anogenital region. Cervical and anal scrapes were collected for cytology and HPV DNA hybridisation. Of the 15 women who practised anal intercourse, a total of 12 (80%) had either clinical or subclinical HPV infection. Seven had overt anal warts, situated either internally or externally in the anal canal; and further 5 women had evidence of subclinical HPV infection as determined by positive cytological and/or HPV DNA hybridisation results on their anal scrapes. The women who did not have a history of anal intercourse had a lower (7/16, 43%), but not statistically significant, rate of anal HPV infection: five had anal warts and two had subclinical evidence of infection. No correlations were found between anal HPV infection and genital (cervical, vulval or vaginal) HPV infection; nor between the HPV typing patterns of women in either group. CONCLUSION--The results obtained from these women do not indicate a close relationship between anal intercourse and the presence of detectable anal HPV infection.     

The acetowhite test in genital human papillomavirus infection in men: what does it add?

BACKGROUND: Many genital human papillomavirus (HPV) infections are clinically invisible epithelial lesions. They remain so for a considerable time before some develop into clinically apparent lesions. The inapparent and asymptomatic nature of these lesions poses a problem in the detection and management of genital HPV infection. Without reliable, and readily available diagnostic methods, no definite therapeutic approach can be recommended or followed. The acetowhite test has been recommended to help determine the extent of the affected area. OBJECTIVE: To evaluate the acetowhite test in detecting inapparent subclinical HPV involvement in male patients with clinically apparent warts. METHODS: Two hundred and two uncircumcised patients with genital warts were included. Patients with concomitant inflammatory lesions were excluded. The warts and adjacent normal skin/mucosa of normal appearance were wrapped in gauze soaked in 5% acetic acid for about 3-5 min. The area was subsequently examined with a hand lens (x 8). RESULTS: All of the 116 hyperplastic warts became acetowhite, as well as a narrow rim of surrounding skin. Few flat warts in dry areas only became dull white and none pure white. No whiteness was observed in the surrounding area. Only 15 of 26 flat warts in moist areas became acetowhite. One (eroded lesion) of 13 verruca vulgaris type lesions and none of the pigmented papules gave positive results to the acetowhite test. CONCLUSIONS: The sensitivity of the acetowhite test for hyperplastic warts is very high, but for other types of warts is low. Detection of subclinical HPV-infected areas is difficult; the acetowhite test did not assist in the identification of additional areas of infection in our patients.     

Detection of human papillomavirus DNA by PCR in semen from patients with and without penile warts.

OBJECTIVES--To determine the prevalence of urethral HPV infection, as indicated by the presence of HPV DNA in semen, in males with and without penile warts. DESIGN--Prevalence study of HPV types 6/11 and 16 DNA using PCR and Southern blot hybridisation analysis of semen. SETTING--Department of Genitourinary Medicine, Blundell Street Clinic, Leeds General Infirmary and the Assisted Conception Unit (ACU) Kings' College, London. SUBJECTS--Patients attending the Genitourinary Clinic for treatment of sexually transmitted diseases including penile warts and males attending Kings' ACU for investigations of infertility. MAIN OUTCOME MEASURES--HPV DNA detected by polymerase chain reaction (PCR) and/or Southern blot hybridisation in semen. RESULTS--HPV DNA was detected by PCR in 23 of 27 (85%) specimens from patients attending the GUM clinic for treatment of genital warts and in one of two specimens from patients attending the clinic for other conditions. By Southern blot, nine (33%) of the 29 specimens from GUM clinic patients were HPV DNA-positive. HPV DNA was detected by PCR in 43 of 104 (41%) of specimens from males attending the ACU, whilst 70 of these tested by Southern blot hybridisation were all negative for HPV DNA. CONCLUSIONS--The data suggest that urethral HPV infections, as indicated by the presence of HPV DNA in semen, are prevalent in males with and without genital warts.     

High prevalence of genital HPV infection among long‐term monogamous partners of women with cervical dysplasia or genital warts—Another reason for HPV vaccination of boys

We conducted a cross‐sectional study on the occurrence of a specific type of genital human papillomavirus (HPV) among long‐term monogamous male partners of women with cervical dysplasia and genital warts. The purpose of the study was to improve knowledge with regards to the management of these couples. The presence of genital HPV‐DNA was detected by PCR with broad spectrum primers followed by hybridization. 82 males met the study criteria, 41 in each group. Genital HPV‐DNA prevalence was 67.5% in the genital warts group and 72.2% in the cervical dysplasia group. The prevalence of high risk HPVs was higher in the cervical dysplasia group, while low risk HPVs were more prevalent in the genital warts group (p < .05). The prevalence of HPV in males was independent of the duration of the relationship (73.5% for 6–24 months and 66.7% for longer relationships). In conclusion, our results suggest that the prevalence of the genital HPV infection in both groups of male partners is comparable and very high, but the spectrum of HPV types varies significantly. The presence of the genital HPV infection in male sexual partners seems to be independent of the duration of the relationship. Applying the HPV vaccination to boys may prevent this phenomenon.     

Managing women with human papillomavirus changes in cervical cytology.

Of 86 women with cervical cytological evidence of human papillomavirus (HPV) infection who underwent colposcopy, 55 yielded histological confirmation of HPV infection and 17 of them had cervical intraepithelial neoplasia (CIN). Of 51 women followed up six months after cryotherapy of their cervical lesions, 46 showed no evidence of HPV infection in their cervices. Of the patients with CIN lesions, only one out of the 16 followed up had persistent CIN II six months after treatment, which gave a clearance rate of 94% for early CIN lesions treated by this method. Of 62 sexual partners examined, 48 had sexually transmitted infections, 38 of them genital warts. The use of colposcopy with directed punch biopsy is a practical way of managing patients whose cervical smears suggest HPV infection. Cryotherapy is effective in treating histologically confirmed cervical HPV and associated minor CIN lesions. Contact tracing and screening for other sexually transmitted diseases is an integral part of managing genital warts.     

Concurrent oral and genital infection with HPV DNA types 6 and 11 in a heterosexual male

Objective Detection of HPV DNA in oral and genital lesions of a heterosexual male. 4 months after oral and vaginal intercourse with a woman with vulvar warts. Passible modes of acquisition of oral HPV infection in the male sexual partner are discussed. Setting Genitourinary Medicine clinic. Methods Polymerase chain reaction amplification of genomic DNA from oral and genital lesions. HPV DNA typing by dot blot hybridization. Results HPV DNA types 6 and 11 were identified in a polypoid tongue lesion and in a penile wart from the male sexual partner. Conclusions The acquisition of oral HPV infection in the male sexual partner may have resulted from genital-oral HPV transfer, either by direct contact with vulvar warts or by digital self-inoculation.     

Pilot study of cervical cytology screening in a sexually transmitted diseases clinic.

A pilot study of cervical cytology was carried out on 500 new patients at the women's sexually transmitted disease (STD) clinic at this hospital. The aim was to discover the incidence of abnormal smears in order to gauge the worth of cervical cytology as a routine clinic procedure. Information was also gathered on each patient's age, sexual history, method of contraception used, previous smears, and genital infection. Smears showing carcinoma in situ, dysplasia, or warty atypia were regarded as abnormal, and the relevant patients were referred for colposcopy. Seventy-three (14.6%) had abnormal smears. Eight women (1.6%), average age 29.7 years, had cervical intraepithelial neoplasia grade III (CIN III) confirmed by histology. One third of the patients with abnormal smears had genital warts, and the incidence of abnormal smears was greater in patients with genital warts than in those without warts. We concluded that STD clinics are useful places in which to carry out cervical cytology screening, and we noted a positive association between infection with genital warts and abnormal smears.