Papillomavirus Lesions Research Articles

Genital human papillomavirus lesions of the male sexual partners: the diagnostic accuracy of peniscopy.

To evaluate the accuracy of peniscopy for identifying human papillomavirus (HPV) lesions in male sexual partners of women with HPV infection. The predictive value of the medical history for HPV infection was also evaluated. Examination of voluntary male partners of the women with HPV infection using colposcopy (peniscopy after acetic acid), cytology and surgical biopsy, the latter being analysed by light microscopy, in situ hybridisation (ISH) and polymerase chain reaction (PCR) for HPV DNA. A detailed medical history was to be taken, too. Department of Gynaecology and Obstetrics, Kuopio University Central Hospital, Finland. A series of 101 voluntary male partners of 101 women invited for examination, treatment and follow-up for their genital HPV infections on the basis of abnormal Papanicolaou (PAP) smears. On peniscopy 64 (63.4%) of the men presented with lesions either typical of (34.7%) or suspicious for (28.7%) HPV infection. Of the latter, 89% were flat lesions mostly undetectable by the naked eye. The cytologic smear was positive in only nine men. On light microscope, 85.7% of the peniscopically typical lesions were found to be consistent with (68.6%) or suspicious for (17.1%) HPV infection. HPV DNA was found in 33 (34.5%) of the 96 typed biopsies, and never in biopsies from peniscopically healthy areas. In logistic regression analysis of the historical data recorded, only the contact time with the current sexual partner was of predictive value for histologically proven HPV infection. Peniscopy is an applicable means for the identification of penile lesions due to HPV infection, but it is not a conclusive diagnostic tool capable of differentiating HPV from non-HPV findings.

Clinical Course of Cervical Human Papillomavirus Lesions in Relation to Coexistent Cervical Infections

Clinical Course of Cervical Human Papillomavirus Lesions in Relation to Coexistent Cervical Infections

5-Fluorouracil exposure during the period of conception: Report on two cases

Two patients who were administered topical vaginal 5-fluorouracil for human papilloma virus lesions became pregnant during treatment. The outcomes in both cases were healthy with normal developmental landmarks at 6 months of age. This experience highlights the potential for a positive outcome.

Expression of Cytokeratin No. 19 Polypeptide in Genital Papillomavirus Lesions

A series of 23 punch biopsies proved to contain human papillomavirus (HPV) type 16 and with established clinical course (including HPV-NCIN, HPV-CIN I, and HPV-CIN II lesion), and 18 additional biopsies of HPV 6-, 11-, 16- or 18-induced genital lesions were analyzed immunohistochemically for expression of cytokeratin No. 19 polypeptide. An immunoperoxidase-ABC technique was used with a polyclonal antibody raised against a synthetic nonapeptide corresponding to the residues 2-10 of the NH2-end, non-alpha-helical region. This polyclonal cytokeratin No. 19 antibody stained mainly (but not exclusively) the basal cells of the normal exocervical epithelium (heterogeneous pattern). Basal cell staining was intense slightly more frequently in HPV-CIN than HPV-NCIN lesions, i.e., ++ or more in 14/24 (58.3%) versus 8/17 (47.0%), respectively. The difference was more marked in the staining of the superficial cells, 70.8 and 58.8% showing intense expression of cytokeratin No. 19, respectively. In 6 (21.4%) of the 28 HPV 16 lesions, basal cell layer was intensely stained, as contrasted to none of the 13 HPV 6, 11 or 18 lesions. The most distinct feature was the well-defined granular staining pattern of the superficial layer in 8 out of 10 HPV 6/11 lesions, as contrasted to the homogeneous pattern in 24 out of 28 HPV-16-infected lesions. In superficial cells, regressed lesions exhibited intense staining in 9/13 (69.2%), as compared with only 4/10 (40%) of the progressed lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Anal and perianal abnormalities in prepubertal victims of sexual abuse

We describe anal and perianal findings in 310 prepubertal children who were determined to be victims of sexual abuse; 206 (66%) had perinea that appeared normal. Abnormal findings were present in 104 children (34%): anal gapping in 61 children; skin tags in 44; rectal tears in 33; sphincter tears in 15; human papillomavirus lesions in 4; perineal scarring in 2; and bite marks in 1. Normal-appearing perianal and anal regions were noted in 150 of 175 children (85%) who denied anal assault, and in 11 of 70 (16%) who described such assault. In comparison, anal and perianal abnormalities were observed in 59 of the 70 children (84%) who gave a clear history of anal assault, but in only 25 of 175 (15%) who denied such abuse. Failure to document perianal abnormalities in almost two thirds of the patients demonstrates the limitations of the medical evaluation in validating allegations of sexual abuse.

Factors associated with progression of cervical human papillomavirus (HPV) infections into carcinoma in situ during a long-term prospective follow-up.

In the course of a prospective study of 508 women with papillomavirus (HPV) lesions of the uterine cervix, 66 lesions that progressed into carcinoma in situ (CIS) were identified and treated by conization during a mean follow-up period of 35 months. The lesions were investigated with light microscopy and with in-situ DNA hybridization using 35S-labelled probes for HPV 6, 11, 16, 18, 31 and 33. After radical cone treatment, 11 of the 66 women (16.7%) have presented with a recurrent HPV infection. The recurrence rate increased with the duration of the follow-up period from less than 10% at the mean follow-up of 25 months to 16.7% at the most recent follow-up at 35 months. Most of these 66 HPV lesions (89%) presented with concomitant CIN in the first punch biopsy, but it is noteworthy that the other 11% presented without concomitant CIN. HPV DNA of at least one of the six types examined was found in 73% of the first biopsies and it is noteworthy that the so-called 'low-risk' types, HPV 6 and 11, were found as frequently as the 'high-risk' types, HPV 16 and 18 (18% and 17%, respectively). This would suggest a similarity in the biological behaviour of these two HPV groups. Although the concept of the 'high-risk' and 'low-risk' HPV types may remain at least partially valid, it is imperative to realize that infection by HPV 6 and 11 by no means excludes the possibility for clinical progression into CIS and eventually to an invasive carcinoma.

Papillomaviruses in lesions of the lower genital tract in Israeli patients

Human papillomaviruses (HPVs) have been strongly associated with benign lesions of the genital tract (condylomata) and with genital cancer of the vulva and cervix. Since the incidence of these lesions in Israel is considered to be low, we have studied the presence of HPV 6, 11, 16 and 18 DNAs in benign, premalignant and malignant tissue samples or gynecological swabs of the lower genital tract. HPV sequences were detected in 48 out of 66 condylomatous lesions ( 72%), 5 11 grades I–II intraepithelial neoplasia ( 45%), 4 6 grade III intraepithelial neoplasia (carcinoma in situ) ( 66.6%) and 8 22 invasive carcinoma ( 36%). The latter included six cases of vulvar carcinoma which were all negative for HPV sequences. No additional HPV types could be detected in any of the tissue biopsies examined. HPV 18 DNA has been found in one vulvar condyloma where it persisted as an episomal molecule, this being the first report of that specific viral DNA in a condylomatous lesion. In all the benign and premalignant lesions containing HPV, the viral sequences were maintained in an episomal state. In two cases of invasive carcinoma, the HPV 16 18 related sequences were integrated in the cellular genome, but in five cases (three containing HPV 16 18 related DNAs and two containing HPV 6 11 related DNAs) the viral sequences were episomal. HPV 16 18 related sequences detected in one out of three cases of vaginal carcinoma were also found to be episomal. This data indicates that human papillomavirus sequences are indeed found in genital lesions of Israeli patients, although to a lesser extent than in other countries, especially for benign lesions and invasive carcinomas. Although HPVs may have a causative role in the development of genital lesions, also in this low tumor incidence area, other factors should be also considered in the etiology of these lesions.

Expression of Cytokeratin Polypeptides in Human Papillomavirus (HPV) Lesions of the Uterine Cervix

A series of 74 punch biopsies, derived from 513 women prospectively followed for cervical human papillomavirus (HPV) infections (including HPV-NCIN, HPV-CIN I, HPV-CIN II, and HPV-CIN III lesions), and 43 control cases (consisting of normal epithelia, nonspecific cervicitis, and classical CIN lesions) were analysed for expression of cytokeratin polypeptides using the ABC technique and monoclonal antibodies SK 56-23 (wide-spectrum antibody), SK 60-61 (specific for keratins 8 and 18), and SK 2-27 (detecting keratins 14, 16, and 17). HPV typing was carried out using the in situ hybridization technique with DNA probes for HPV 6, 11, 16, 18, and 31. All layers of the exocervical epithelium were regularly stained with the antibody SK 56-23, and the staining pattern remained unaltered in all cervical lesions studied. In contrast to the normal exocervical epithelium, which remained negative with SK 60-61, positive staining was observed in 3 of 15 cervicitis cases and 6 of 23 classical CIN lesions. Interestingly, the majority (69 of 74, 93.2%) of both HPV-NCIN and HPV-CIN lesions showed positive staining with this antibody either in all layers or in suprabasal cells. Antibody SK 2-27 stained the basal cells of the normal exocervical epithelium with remarkable specificity. In 18 of 19 HPV-NCIN lesions, basal cells could not be stained by SK 2-27 monoclonal, but the suprabasal cells were stained instead. In HPV-CIN, but not in classical CIN, this antibody demonstrated the presence of the epitope typical of the cytokeratins 14, 16, and 17 in all layers of the epithelium, the highest frequency (9 of 12, 75%) being found in HPV 16-induced lesions. These disturbances of cytokeratin patterns in cervical epithelium could be associated with cell transformation by HPV, leading to development of HPV-CIN, and could be specific for this virus. The present data are of interest in assessing the stage of maturation of the squamous cells in progressing cervical HPV infections.

Type IV collagen in the basal membrane of human papillomavirus associated premalignant and malignant squamous cell lesions of the uterine cervix.

In the present study, the expression of type IV collagen associated with the basal membrane (BM) was studied histochemically (indirect immunoperoxidase-antiperoxidase) in cervical human papillomavirus (HPV) lesions (diagnosed using in situ DNA hybridization) of different grades. The expression of type IV collagen in premalignant epithelial lesions (HPV with and without cervical intraepithelial neoplasia) was identical with that in the BM of normal exocervical epithelium, in contrast to 60% (3/5) of carcinoma in situ lesions and 90% (10/11) of invasive carcinomas, where the staining pattern was interrupted and the staining intensity reduced. Thus, the expression of type IV collagen seems to remain unchanged during the entire spectrum of premalignant stages of cervical HPV lesions. This suggests that the squamous epithelial cells responsible for the formation of the BM are not affected by this virus at early stages of the disease, and immunohistochemical recognition of an intact staining pattern of type IV collagen may signify well-preserved basal cell function (confined to nonmalignant?) HPV-infected squamous epithelium.

Altered expression of filaggrin in human papillomavirus (HPV) lesions of the uterine cervix.

A series of 64 punch biopsies collected from women prospectively followed-up for cervical Human papillomavirus (HPV) infections (with and without CIN), and 38 control biopsies (normal epithelia, and classical CIN) were analysed for expression of filaggrin (a histidine-rich protein constituent of keratohyalin granules) using the ABC technique and polyclonal antibody. HPV typing was completed using the in situ hybridization technique with DNA probes for HPV 6, 11, 16, 18 and 31. Three patterns of filaggrin distribution were differentiated: pattern I, all layers above the basal cells stained positive regularly; pattern II, all layers above the basal cells stained irregularly, and pattern III, scattered superficial cells stained positive. There was a significant difference between HPV-noCIN and HPV-CIN lesions in their filaggrin patterns, pattern I being present in the majority (77.7%) of HPV-noCIN lesions, as contrasted to HPV-CIN lesions, where pattern III was the predominant one (43.5%), followed by pattern II (32.6%). In HPV-CIN as well as in CIN lesions, pattern I was inversely related to the grade of CIN, being entirely absent in HPV-CIN III and CIN III. A significant difference exists between CIN and HPV-CIN lesions, concerning the presence of pattern III (4.3% and 43.5%, respectively, P less than 0.001). The difference was less dramatic with regard to pattern I (30.4% and 21.7%, respectively, P less than 0.05). In the lesions containing HPV 6, 11 or 31 DNA, filaggrin distribution was shown to be more close to that of the normal epithelium (I 36.7%, and II 34.7%), while in the HPV 16 and 18-infected cases, pattern III was the predominant one (46.7%). The assessment of filaggrin pattern in HPV lesions might be of help in evaluating the severity of the disturbance of keratinocyte differentiation induced by the progression of HPV infections.

Human papillomavirus and lower genital neoplasia in renal transplant patients : Halpert R; Fruchter RG; Sedlis A; et al. Department of Obstetrics and Gynecology, State University of New York, Downstate Medical Center, Brooklyn, NY, USA Obstet. Gynecol.; 68/2 (251–258) 1986

Lower genital cytopathology was evaluated in 105 immunosuppressed renal transplant recipients. Evidence of human papillomavirus infection was found in 17.5% and of lower genital neoplasia in 9.5%. The rate of the virus infection in the immunosuppressed was nine times greater than in a general population and 17 times greater than in a matched immunocompetent population. The rate of cervical neoplasia was 16 times greater than in a general population and nine times greater than in a matched immunocompetent population. In one-third of patients with human papillomavirus lesions and one-half of patients with neoplastic lesions, multiple lower genital sites were also involved. Of risk factors evaluated, only the number of sexual partners was associated with the development of human papillomavirus/lower genital neoplasia.

Chlamydial infections and human papillomavirus lesions in women with cervical intraepithelial neoplasia

Chlamydial infections and human papillomavirus lesions in women with cervical intraepithelial neoplasia

Nuclear DNA analysis of koilocytic and premalignant lesions of the uterine cervix.

Cervical biopsy samples were taken from 79 patients who had various grades of cervical intraepithelial neoplasia or who showed evidence, in the form of koilocytosis, of human papillomavirus infection of the uterine cervix and from 10 women with normal cervices. The DNA content of the cells in the samples was analysed by flow cytometry. Analysis of the data obtained showed that the biopsy samples from women with cervical intraepithelial neoplasia and human papillomavirus lesions contained significantly more dividing cells (31.2% of cells from human papillomavirus lesions with no cervical intraepithelial neoplasia and 33.06%, 29.89%, and 31.76% of cells from cervical intraepithelial neoplasia grades I, II, and III, respectively) than those from women with normal cervices (21.6%). The proportion of aneuploid samples from the group who showed evidence of human papillomavirus infection only (18.2%) did not differ significantly from the group with cervical intraepithelial neoplasia grade III (21.2%). Aneuploidy and an increased rate of cellular proliferation are recognised characteristics of malignancy. These results therefore support the view that human papillomavirus plays an important part in the aetiology of cervical carcinoma and are relevant to the clinical management of patients.

Coexistent chlamydial infections related to natural history of human papillomavirus lesions in uterine cervix.

To assess the role of Chlamydia trachomatis in the development of cervical intraepithelial neoplasia (CIN) and to evaluate possible synergism between chlamydiae and human papillomavirus (HPV) in this process, 418 women who had been prospectively followed up for cervical HPV infections at our clinic since 1981 were tested for chlamydiae. At each visit the patients were examined by colposcopy, and other investigations, such as Papanicolaou (Pap) smears, punch biopsies, urethral, and cervical swabs, were undertaken as indicated. In biopsy specimens the cytopathic changes of HPV, concomitant CIN, and the local immunocompetent cell infiltrates were analysed. The latter were measured and further identified using an alpha naphthyl acetate esterase (ANAE) technique to define B cells, macrophages, and T cells and using monoclonal antibodies to define T cell subsets, NK (natural killer cells), and Langerhans cells. Chlamydial isolation (4.1% in the cervix, and 3.6% in the urethra) did not positively correlate with the degree of cytological atypia in PAP smears or with the degree of CIN lesions associated with HPV. Chlamydial cervicitis did not affect the ANAE definable cell composition of the immunocompetent cell infiltrates in HPV lesions, or that of the immunocompetent cell subsets, including the ratios of T helper to T suppressor cells and the numbers of NK cells. Chlamydial infection did not alter the natural history of HPV lesions, of which 30% regressed, 53% persisted, and 17% progressed during follow up. The present results do not provide evidence to substantiate the hypothesis that chlamydiae and HPV might act synergistically in cervical carcinogenesis, or the view that C trachomatis may be a major aetiological agent of CIN lesions. Chlamydiae and HPV are covariables of sexual behaviour, and their concomitant appearance in sexually promiscuous women is best explained by this fact. As we do not have more direct evidence for the oncogenic potential of C trachomatis (as we have of HPV), it seems reasonable to consider that this agent is not a major cause of CIN, but rather a sexually transmitted agent commonly found in women with CIN because of their promiscuous sexual behaviour.

Colposcopy in assessment of the natural history of prospectively followed-up human papillomavirus (HPV) lesions in the uterine cervix.

As a part of the long-term prospective follow-up study conducted in our clinic since 1981 for women with cervical HPV (Human papillomavirus) infections (either with or without cervical intra-epithelial neoplasia, HPV-CIN and HPV-NCIN, respectively) the colposcopic data on 292 consecutive patients with a mean follow-up of 16 months are reported. The results are based on 786 colposcopies performed at 6-month intervals according to conventional methods. Colposcopic findings are categorized into one of the following patterns: normal, warty, punctate, mosaic, leukoplakia, and combination. Colposcopic pattern bore an excellent correlation to the natural history (clinical course) of the HPV lesions, in that colposcopy was normal in 75% of the regressing lesions, in 38% of the persistors, and in only 16% of the progressors. The percentage of regression increased parallel with the frequency of normal pattern during the follow-up. Leukoplakia and combination were the two most frequent (55.7%) patterns in progressor lesions, as compared with only 12.9% in regressors and in 33.2% of the persistors. The same was true of the 15 lesions progressing into carcinoma in situ (CIS), and treated by cone. In the progressor lesions, an abnormal colposcopy pattern was disclosed in 65-100%, as compared with 14-35% only in the regressors. The present study provides evidence that colposcopy is an applicable and relatively accurate diagnostic method for assessing cervical HPV lesions. Colposcopy also seems to have some prognostic value in the follow-up of these lesions, as shown by the fact that normal colposcopic pattern is frequently associated with regression, whereas leukoplakia and combination are encountered more frequently than others in HPV lesions with CIN, shown to be more prone to progress during the follow-up.

Natural killer (NK) cells with HNK-1 phenotype in the cervical biopsies of women followed-up for human papillomavirus (HPV) lesions.

Local immunocompetent cell infiltrates in 263 cervical punch biopsies of women followed-up since 1981 (16 +/- 14 months, M +/- SD) for an established Human papillomavirus (HPV) lesion with or without concomitant cervical intra-epithelial neoplasia (CIN) were analysed for presence of human natural killer (NK) cells, defined by the monoclonal antibody HNK-1 (Leu-7) using the avidin-biotin peroxidase complex (ABC) technique. HNK-1+ cells remained at a constant low level (1.8 to 3.0% of the cells) in the different types of HPV lesions (flat, inverted, or papillomatous condylomas), their percentages (range 1.3 to 2.5% of cells) remaining similarly unaffected by the severity of associated CIN. As shown to be the case with human NK cell function in the peripheral blood, the percentages of local HNK-1+ cells did not evidence any age-dependence. Furthermore, the intensity of the infiltrate did not correlate with the relative levels of HNK-1+ cells in the biopsies. Slightly (but not significantly) higher levels (2.5%) of HNK-1+ cells were found in the first biopsies of the HPV lesions found to regress during the follow-up period (28.8% of cases), when compared with those (1.7% and 1.8%, respectively) in persisting lesions (52.1% of cases) or progressing lesions (19.1% of lesions). The results are discussed in terms of the proposed immune surveillance function of human NK cells in malignant growths, and the conclusion is drawn that the present study does not provide any firm evidence to suggest that local NK cell function would contribute significantly to the clinical behavior of the cervical HPV lesions.

Natural history of cervical human papillomavirus (HPV) infections based on prospective follow‐up

To assess the natural history of human papillomavirus (HPV) lesions in the uterine cervix, a prospective follow-up of untreated lesions has been conducted since late 1981. The present report summarizes the data on 343 women with cervical HPV lesions currently followed-up for a mean of 18.7 (SD 15.2) months by colposcopy and PAP smears (group B) or by additional punch biopsy (group A). Initially these two groups were classified on the first PAP smears, presenting with HPV-induced cytopathic changes, and either with (group A) or without (group B) concomitant changes suggestive of cervical intraepithelial neoplasia (CIN). The clinical course of the HPV lesions could not be predicted adequately from the findings of the first PAP smears, as evidenced by the higher progression rate (15.4%) in the 214 women initially classified in group B, compared with 11.6% in the 129 women classified in group A. Furthermore, the number progressing to carcinoma in situ requiring conization was equal (seven patients) in the two groups. This necessitated a more flexible approach to follow-up, permitting transfer of patients between groups, which resulted in a final allocation of 261 women to group A, and 82 to group B. To date, 25% of the total of 343 HPV lesions have regressed, 61% have persisted, and 14% have progressed. Of the latter, a total of 14 (4.1%) have been coned due to progression to carcinoma in situ. The rate of regression seems to be inversely related, and progression directly related, to the degree of HPV-associated CIN.(ABSTRACT TRUNCATED AT 250 WORDS)

Papillomavirus lesions in immunodepression and immunosuppression

Papillomavirus lesions in immunodepression and immunosuppression

Regression of flat warts and common warts

Wart (human papilloma) is such a common disease that even a child can make a diagnosis at a glance. Furthermore, from our long experience, we are aware that warts often disappear in a short period of time, spontaneously or after various magical rituals that are prevalent in different parts of the world. In Japan, we can find some shrines or temples in every district where ardent worshipers make pilgrimages in search of quick answers to their prayers to cure their warts. Evaluation of clinical effectiveness of a new therapeutic modality is most difficult because of its high incidence of spontaneous wart resolution. The lesion can be cured even by hypnosis. Recently, the phenomenon of spontaneous regression of warts was reviewed from the viewpoint of tumor immunology. We now know that in the body, tumors may be rejected by an immune “surveillance” mechanism analogous to resistance to microbial pathogens. Various modalities of immunization procedure or enhancement of host immunity can induce partial or complete resolution of established tumors in both experimental animals and humans. Even malignant tumors, such as melanoma or choriocarcinoma, may disappear spontaneously. Wart is one of the most common tumors in humans and probably the tumor that most commonly shows the phenomenon of spontaneous regression. Advances in molecular biology and biotechnology have disclosed that, as there are various clinical types of wart, there are many distinct HPV types and that the distinct HPV types are associated with distinct cutaneous and mucosal papillomas. 1 Analogous to animals with the Shope papillomavirus or bovine papillomavirus infections, it is known that some human papillomavirus lesions may undergo malignant transformation. 2,3

Immunophenotypes of lymphocytes in prospectively followed up human papillomavirus lesions of the cervix.

From 1981 286 women were prospectively followed up for a mean (SD) of 16 (14) months for established infection with human papillomavirus (HPV) with or without coexistent cervical intraepithelial neoplasia (CIN). The in situ immunocompetent cell infiltrates in 263 cervical punch biopsy specimens from these women were phenotypically identified by the avidinbiotin peroxidase complex (ABC) technique using monoclonal antibodies Leu-10, OKT-3, OKT-4, and OKT-8. Leu-10+ B lymphocytes far outnumbered the OKT-3+ T lymphocytes in all types of HPV lesions (flat, inverted, and papillomatous condylomas of the cervix). The ratio of OKT-4+ to OKT-8+ (T helper to T suppressor cells) was slightly reduced in HPV lesions with more severe CIN and correlated positively with the intensity of the immunocompetent cell infiltrate. The ratio of OKT-4+ to OKT-8+ cells was highest in the 47 (28.8%) patients with HPV lesions that regressed during follow up, somewhat lower in the 85 (52.1%) with persistent lesions, and lowest in the 31 (19.1%) with lesions showing clinical progression. The results are discussed in terms of the proposed immune surveillance functions attributed to immunocompetent cells in situ according to the mucosal associated lymphatic tissue (MALT) concept. The conclusion drawn is that a dynamic balance between the immunoregulatory cells and their subtypes is a prerequisite for the proper handling of intracellular infections of the mucosa, including that with HPV.