Ductal carcinoma in-situ arising in mammary-like glands of the vulva.

Recently a variant of cutaneous glands has been recognized in the anogenital region that combines the morphologic and immunohistochemical features of eccrine, apocrine, and mammary glands, so-called 'mammary-like glands of the vulva'. Carcinoma arising in mammary-like tissue of the vulva is a rare occurrence. So far, there have been 11 cases of primary, mammary-type invasive carcinoma and one case of in-situ carcinoma reported in the vulva. We describe an unusual case of ductal carcinoma in-situ without invasion arising in mammary-like glands of the vulva. A 57-year old woman presented with a 1-year history of a 1 cm nodule in the right labium majus. Excision showed ductal carcinoma in-situ with cribriform and papillary morphology in an adenosis-like lesion associated with mammary-like glands. No invasion into the stroma was identified. Immunostains were positive for gross cystic disease fluid protein 15 (GCDFP-15) and estrogen and progesterone receptors. An extensive survey including bilateral mammograms was negative. One year postoperatively, the patient shows no evidence of disease. To our knowledge, this represents the second case of DCIS associated with mammary-like glands of the vulva reported in the English literature.     

Human papillomavirus and cervical lesions

Human papillomavirus (HPV) infection has been implicated in the intraepithelial cervical changes that cause most abnormal Papanicolaou smears. To date, 14 types of HPVs have been identified. All are small, nondeveloped, icosahedral DNA viruses that share a common internal antigen. In cases of cervical HPV infection, the koilocytes and dyskeratocytes are the most frequently seen cell types. Most infections are flat aceto-white lesions. Florid condyloma acuminatum, usually detectable with the naked eye, is characterized by an irregular surface secondary to finger-like projections, in the middle of which a capillary loop comes to the surface. Spiked condyloma, not seen with the naked eye, has an irregular surface that shows asperity. 3 techniques have been used to differentiate atypical condyloma from intraepithelial neoplasia: microspectrophotometric studies, the peroxidase- antiperoxidase technique, and electronmicroscopy. There is growing evidence that papillomaviruses play an etiologic role in human genital cancer. 20-25% of dysplastic and neoplastic lesions show a coexistence of condylomas of the cervix or vulva with dysplasia or neoplasia. Epidemiologic research suggests that cervical condylomas occur at a mean age of 27.5 years, precede cervical dysplasia by 3.3 years, carcinoma in situ by 9.3 years, and invasive carcinoma by 27.4 years. The conversion of most cases of papillomas into squamous cell carcinomas requires the presence of carcinogenic initiators, 1 of which is believed to be herpes simplex virus.     

Human papillomavirus infection and anogenital neoplasia: speculations for the future

HPV infections of the female genital tract are common. The association of these viruses with anogenital neoplasia has stimulated efforts to devise practical methods of detection and typing of HPV. Although experimental diagnostic tests are available, they are, for the most part, complex and time consuming and are limited to medical centers researching HPV. New methods for preparing probes with higher sensitivities for hybridization tests will allow use of in-situ methods on formalin-fixed tissues and will probably be the method of choice. Antigen detection systems are not available except for antisera directed against the common structural antigens. The most useful immunologic test will be directed toward detection of nonstructural antigens in fixed tissues; such a system could also be useful for virus typing. Therapies based on use of these antigens to stimulate the immune system may be applicable as an alternative to current therapies. Most intriguing are the prospects for a vaccine based on either structural or nonstructural viral antigens. It has been estimated that as many as 20 per cent of female cancer deaths worldwide are associated with HPV. Thus, use of an effective vaccine would relieve considerable human suffering. However, until the host immune response to HPV infection is better defined, much of the effort dedicated to developing a vaccine may be futile.     

Human papillomavirus infection of the cervix: relative risk associations of 15 common anogenital types.

During the years 1982-1989, 2627 women were recruited into eight studies analyzing the relationship between human papillomavirus (HPV) infection and cervical neoplasia. Subsequently, each individual was assigned as either a case or control, and each cervical sample was rescreened for HPV DNA by low-stringency Southern blot hybridization. Positive samples were retested at high stringency with specific probes for HPVs 6/11, 16, 18, 31, 33, 35, 42, 43, 44, 45, 51, 52, 56, and (in most instances) 58. Most cases (153 cancers, 261 high-grade and 377 low-grade squamous intraepithelial lesions) had target or cone biopsies; all 270 borderline atypia subjects and more than 85% of the 1566 normal controls had cytology plus colposcopy/cytology. Scientists performing HPV testing were masked to the clinical diagnoses. Human papillomavirus DNA was detected in 79.3% of specimens from women with definite cervical disease (627 of 791), in 23.7% of borderline atypia subjects (64 of 270), and in 6.4% of normal subjects (101 of 1566). Graphic analysis of odds ratios at each point in the diagnostic spectrum defined four categories: 1) "low risk" (HPVs 6/11, 42, 43, and 44), present in 20.2% (76 of 377) of low-grade lesions but absent in all 153 cancers; 2) "intermediate risk" (HPVs 31, 33, 35, 51, 52, and 58), detected in 23.8% (62 of 261) of high-grade squamous intraepithelial lesions but only 10.5% (16 of 153) of cancers; 3) "high risk/HPV 16," associated with 47.1% of both high-grade intraepithelial lesions (123 of 261) and cancers (72 of 153); and 4) "high risk/HPV 18" (HPVs 18, 45, and 56), found in 26.8% (41 of 153) of invasive carcinomas but only 6.5% (17 of 261) of high-grade intraepithelial lesions. The presence of an oncogenic HPV type conferred relative risks ranging at 65.1-235.7 for the occurrence of a high-grade lesion and 31.1-296.1 for an invasive cancer.     

Human papillomavirus in the oral mucosa of women with genital human papillomavirus lesions

OBJECTIVES: Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases worldwide. We determined the frequency of HPV in the oral cavity of women with and without genital HPV lesions. MATERIAL AND METHODS: All patients were seen at the Department of Gynecology, Women's Health Center and the State University of Campinas, Sao Paulo, Brazil and submitted to a general physical and gynecological examination plus an evaluation of the oral cavity. Detailed histories investigated their sexual practices. HPV in the oral cavity was determined by polymerase chain reaction using consensus primers in 70 women presenting with histopathology-confirmed clinical HPV lesions in the genital region and 70 women negative by gynecological, colposcopic and cytological examination for clinical or subclinical HPV lesions. RESULTS: Oral HPV was detected in 29 (20.7%) of the subjects. Among the positive women, 26 (89.7%) were also positive for genital HPV as opposed to only 3 (2.7%) who were genital HPV-negative (p < 0.0001). The overall prevalence of HPV in the oral cavity of patients with and without genital HPV was 37.1 and 4.3%, respectively, (p < 0.0001). The presence of oral HPV was unrelated to the practice of fellatio (22% versus 19%). CONCLUSION: Patients with HPV genital infection have a greater frequency of HPV in their oral mucosa.     

Adenocarcinoma of mammary-like glands in the vulva successfully treated by weekly paclitaxel

An 87-year-old was referred for gynecologic evaluation of a lesion involving the left labia majus noted 3 years earlier. Fine-needle aspiration cytology revealed clusters with an acinous structure or glandular formation. The tumor appeared as cell clusters with linear arrangements. Histologic examination showed the same morphologic findings as scirrhus type of primary breast carcinoma. Examinations of the breasts and axillary lymph nodes were normal. This disease was diagnosed as an adenocarcinoma arising in mammary-like glands of the vulva. Bone scan showed multiple foci in the sternum, costa, and vertebrae, consistent with metastatic disease. We administered five courses of weekly paclitaxel chemotherapy, which achieved a partial response. There were no severe adverse effects. In our case, the fine-needle aspiration cytology was a rapid and minimally invasive method of diagnosis, and the findings were extremely similar to those of the scirrhus type of primary breast carcinoma. Rapid and accurate diagnosis made with this technique might contribute to a good prognosis in the early-staged cases. Weekly paclitaxel chemotherapy may be one of the safe and effective treatments for this disease with distant metastases, even in extremely aged patients (over 80 years).     

Human papillomavirus.

In the past year, new data have been published on the molecular biology of human papillomavirus infections and their relationship to cervical neoplasia. As molecular techniques have become more sophisticated and as the molecular knowledge of human papilloma-virus infections has been pursued in greater depth, it is increasingly apparent that this human tumor DNA virus is similar to a number of other oncogenic DNA viruses that have been described and well studied. These viruses appear to act through a common pathway of producing oncogenic proteins that interfere with key signalling elements that normally control the process of cell division. With a better mechanistic knowledge, it should be possible to design new therapeutic approaches to treating human papillomavirus-associated disease that are directed toward specific cellular events such as turning off the production of E6 and E7 proteins or restoring the activity of pRB or p53. Increased attention has also been turned to immunologic aspects of HPV infections, and a number of groups are eagerly pursuing the possibility of using simple office-based procedures to detect specific proteins encoded for by the human papillomavirus open reading frames in an attempt to determine who has been infected, is actively infected, and has proteins being produced that are indicative of neoplasia. From the clinical point of view, the use of outpatient excisional techniques such as the loop electrosurgical excision procedure is rapidly supplanting ablative techniques because of their superior ability to identify early invasive carcinomas and adenocarcinomas in situ that have not been detected by colposcopy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human papillomavirus testing in the clinical laboratory. Part I: squamous lesions of the cervix

The aim of this study was twofold: (1) to evaluate the contribution of viral (HPV) testing for improving the sensitivity of cervical cytology and (2) to correlate HPV types with the histology of the detected cervical cancer precursors, particularly the low-grade, CIN I variant. We used the dot blot hybridization technique (ViraPap) and polymerase chain reaction (PCR) in 63 women referred to our colposcopy clinic for evaluation of an abnormal Pap test. Histopathologic samples obtained by multiple colposcope-directed punch biopsies were used for a diagnostic gold standard. Among the 53 women with histologically proven CIN, precolposcopy cytology was positive in 38 (72%) compared to 53% and 60% HPV positivity by ViraPap and PCR, respectively (p less than 0.01). When the yields of ViraPap/PCR and cytology were combined, however, the detection rate of CIN was 91%, a significant improvement over cytology alone (p less than 0.02). HPV DNA was found either by ViraPap or PCR in 45 of 63 (71%) biopsy specimens, and 37 of 38 (97%) HPV-positive CIN, including the low-grade CIN I variant, contained oncogenic HPV types. HPV type 16 was present in 22 of 38 (58%) CIN lesions and mixed with HPV 6/11, 18, or the 30s group in 6 of 38 (16%) of the cases. HPV 6/11 alone was found only in 1 case of CIN I (2.7%). HPV testing by molecular technology increases the sensitivity of cytology.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human papillomavirus

Human papillomaviruses are ancient small DNA viruses and represent the most common sexually transmitted infection in the world. In the majority, HPV infection is cleared by an incompletely understood immune response. HPV is a necessary but not sufficient cause of cervical cancer, and responsible for a proportion of other anogenital cancers including vulval, vaginal, anal and oropharyngeal. Oncogenesis is likely mediated through viral proteins which hijack host-cell machinery in epithelial keratinocytes and disrupt host tumour-suppressor proteins. Much work has been undertaken to further characterise the natural history of HPV infection and cervical disease. Such efforts have been translated to important public health interventions like the introduction of HPV tests in cervical screening. HPV vaccination programmes are expected to further reduce the incidence of high-risk HPV infections and resultantly HPV-related disease.     

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)     

Human papillomavirus infection and cervical ectopy.

OBJECTIVES: To investigate the prevalence of human papillomavirus (HPV), and HPV type 16 (HPV16) infection in cervical ectopy, and the presence of anti-HPV16 secretory IgA (sIgA) antibodies. METHODS: DNA from patients with cervical ectopy (n=218), HPV-associated lesions (n=111), and controls without evidence of cervical ectopy or HPV infection (n=93) were analyzed by PCR for the presence of HPV and HPV16. The presence of mucosal sIgA antibodies against HPV16 capsid antigens (VLP) was assayed in cervical mucus by ELISA. RESULTS: Prevalence of HPV DNA was higher in cervical ectopy than in controls (P=0.04; OR=2.06; 95% CI 0.99-4.33). HPV16 was 6.3 times more prevalent in cervical ectopy than in controls. Anti-HPV16 sIgA were detected more frequently in cervical ectopy patients than in controls (P=0.0004). CONCLUSIONS: Cervical ectopy correlates with HPV infection. HPV16 is highly prevalent in cervical ectopy. sIgA antibodies against HPV16 capsids are generated in patients with cervical ectopy.     

Human papillomavirus types and cervical squamous intraepithelial lesions that recur after cold-knife conization

The purpose of this study was to analyze the HPV types and histological margins of cervical squamous intraepithelial lesions (SILs) treated by cold-knife conization and to correlate this with recurrent disease. Of 203 cone biopsies done for SILs primarily because the entire lesion could not be visualized at colposcopy, follow-up information was available for 85 cases. Of these 85 cases, biopsy-proven recurrences were documented for 10 (12%) women. In the SILs which recurred after conization, the lesion was noted on the surgical margin in 7/10 (70%) cases. In contrast, SILs that did not recur after cold-knife conization were detected on the surgical margin in only 12% of cases. In 7 of the recurrences, the HPV type detected in the pretreatment SIL was the same as that detected in the SIL that occurred after conization. In the other 3 recurrences, one of either the primary or recurrent SILs was HPV positive and the other corresponding lesion HPV negative. It is concluded that detection of a SIL on the surgical margin is a marker for recurrent disease and that recurrences are often associated with the same HPV type as that noted in the pretreatment SIL.     

Human papillomavirus in amniotic fluid

Background

There is evidence to suggest that human papillomavirus (HPV) can cross the placenta resulting in in-utero transmission. The goal of this study was to determine if HPV can be detected in amniotic fluid from women with intact amniotic membranes.

Methods

Residual amniotic fluid and cultured cell pellets from amniocentesis performed for prenatal diagnosis were used. PGMY09/11 L1 consensus primers and GP5+/GP6+ primers were used in a nested polymerase chain reaction assay for HPV.

Results

There were 146 paired samples from 142 women representing 139 singleton pregnancies, 2 twin pregnancies, and 1 triplet pregnancy. The women were 78% Caucasian, 5% African American, 14% Asian, and 2% Hispanic. The average age was 35.2 years with a range of 23–55 years. All samples were β-globin positive. HPV was not detected in any of the paired samples.

Conclusion

Given the age range, race, and ethnicity of the study population, one would anticipate some evidence of HPV if it could easily cross the placenta, but there was none.     

Viral load of high-risk human papillomavirus in cervical squamous intraepithelial lesions.

OBJECTIVES: This case-control study was conducted to investigate the role of viral load of high-risk human papillomaviruses (HPVs) in the development of cervical squamous intraepithelial lesions (SILs) and invasive cancers. METHODS: A total of 30 female cases who had histological evidence of low-grade SIL (n=10) or high-grade SIL and above (n=20) were identified as the case group at the Tri-Service General Hospital, Taipei between September 1998 and March 1999. In addition, 80 female controls who had normal cervical cytology were enrolled and individually matched on age (+/-5 years) and date of recruitment to each case. Cervical swabs collected from study subjects were tested for the positivity and viral load of high-risk HPVs by Hybrid Capture II assay. Additionally, subjects completed a risk factor questionnaire. RESULTS: Among sex behavioral factors studied, younger age at first intercourse was associated with a significantly elevated risk of cervical SIL and invasive cancers. With respect to HPV infection, high-risk HPV DNA was present in 70% (21/30) of case and 21% (17/80) of control subjects, resulting in an odds ratio (OR) of 6.6 [95% confidence interval (C.I.)=2.6-17.0]. Moreover, women who had a high viral load were at significantly greater risk for cervical SIL and invasive cancers than those who were infected with a low viral load (OR=18.0, 95% C.I.=3.0-108.5). CONCLUSIONS: Among the variables tested, infection with a high viral load of high-risk HPVs is the strongest determinant for cervical SIL and cervical cancers in Taiwan.     

Human papillomavirus (HPV) genotyping by HPV DNA chip in cervical cancer and precancerous lesions

OBJECTIVES: The human papillomavirus (HPV) is a well-known cause of cervical cancer. HPV tests are used as an adjunct test to decrease the false-negative rate of cytological screening. However, attempts are being made to replace the cytological screening with HPV tests. Therefore, this study was performed to examine the possibility of using HPV tests as screening test. MATERIALS AND METHODS: The results of the tests that were performed at the same time including the ThinPrep cytology, the high-risk group hybrid capture II (HC-II) test, the HPV DNA chip (HD-C) test, and a punch biopsy were compared in 400 women who were referred to us due to abnormal cytology or cervicogram. The accuracy of each test was then evaluated, and the type of virus was investigated using a HD-C test. RESULTS: The positive predictive values detected by the high-risk group HC-II test and HD-C test according to the histological diagnosis outcomes were 56.8 and 53.8%, respectively, for cervicitis; 91.5 and 91.5%, respectively, for cervical intraepithelial neoplasia I (CIN I); 88.1% and 81.0%, respectively, for CIN II; 88.6 and 84.2%, respectively, for CIN III, and 92.5 and 88.7%, respectively, for cancer (in 53 patients). The most prevalent types of HPV according to the HPV tests were types 16, 58, 18, and 52 in which type 16 was detected in the more advanced lesions. The sensitivity was 88.4% for the ThinPrep cytology, 89.9% for the HC-II for the high-risk group, and 86.2% for the HD-C test. CONCLUSION: These results suggest the possibility of using the HC-II and HD-C tests as screening tests, which have a similar sensitivity as the ThinPrep cytology. Nonetheless, randomized controlled trials will be needed before the actual application of the HPV tests as screening tests. Despite the fact that the importance of HPV type 16 in cancer development was confirmed, the prevalence of types 58 and 52 were relatively high compared with those found in other studies, showing a need for further studies on this subject. These HPV types need to be considered in vaccine development.