PubMed Health⌕ Search

Biomedical subjects

C P Crum

Publications and source records attributed to C P Crum.

At least 109 records · Page 6Linked to original sources

Papillomavirus and vulvovaginal neoplasia.

Cumulative evidence strongly implicates human papillomavirus (HPV) in the genesis of squamous neoplasia of the lower female genital tract, including the vulva. The association of HPV with neoplasms at that site includes the relationship of specific HPV types with neoplasms and evidence that those HPV DNA types can transform epithelial cells in vitro. The capacity for in vitro transformation has been isolated to specific regions of the HPV genome. That may be unique in cancer-associated viruses. Nevertheless, epidemiologic evidence points to additional factors, including immunologic, habitual and environmental, that may play an important role in the development of lower genital tract carcinomas. In particular, the marked differences in mean age and other variables between women with vulvar precancers and invasive cancer suggest that the evolution of invasive cancer involves more than HPV infection alone. Hence, the prevention of invasive vulvar cancer in older age groups will require an understanding of the unique host factors that render a small group of women susceptible to the disease in the face of an epidemic of HPV infection in the population at large.

Female↗

Histological correlates of clinically occult human papillomavirus infection of the uterine cervix.

Occult infection of the uterine cervix by human papillomavirus (HPV) is assumed when viral DNA sequences are detected from cervical swabs but no lesion is detectable and the Papanicolaou smear is negative. In an attempt to identify what histological changes correlate with occult infections, DNA was extracted from 200 cervical swabs taken from hysterectomy specimens. The DNA was analyzed by Southern blot hybridization for the presence of HPV sequences. Eleven cases (5.5%) were positive. The entire cervix from each case as well as from 28 negative cases was processed for histological analysis. One of the positive cases contained a CIN 2 lesion. The other 10 showed parakeratosis, papillomatosis, acanthosis, as well as focal nuclear pleomorphism and perinuclear halos (borderline koilocytotic atypia) in proportions equal to the negative controls. In situ hybridization analysis of the cases that showed borderline koilocytotic atypia were negative. These findings confirm that clinically and cytologically occult HPV infection of the uterine cervix is not associated with diagnostic histological changes. This underscores the need for caution when interpreting cervical biopsies that show changes suggestive, but not absolutely diagnostic, of HPV infection. Further, the precise epithelial location of the virus remains unclear.

Adult↗

Accumulation of RNA homologous to human papillomavirus type 16 open reading frames in genital precancers.

The accumulation of human papillomavirus type 16 (HPV-16)-specific RNAs in tissue sections from biopsies of patients with genital precancers was studied by in situ hybridization with single-stranded 35S-labeled RNA. These analyses revealed that the most abundant early-region RNAs were derived from the E4 and E5 open reading frames (ORFs). RNAs homologous to the E6/E7 ORFs were also detected, whereas RNAs homologous to the intervening E1 ORF were not. This suggests that the E4 and E5 mRNAs are derived by splicing to the upstream E6/E7 ORFs, consistent with studies of HPV-11 in condylomata (L. T. Chow et al., Cancer Cells (Cold Spring Harbor) 5:55-72, 1987). Abundant RNAs homologous to the 5' portion of L1 were also detected. These RNAs were localized to the apical strata of the epithelium. HPV-16 RNAs accumulated in discrete regions of these lesions, and when present were most abundant in the upper cell layers of the precancerous epithelium. RNAs homologous to early ORFs were also detected in some germinal cells within the basal layer of the epithelium.

Epithelium↗

Isolation of a novel human papillomavirus (type 51) from a cervical condyloma.

We cloned the DNA from a novel human papillomavirus (HPV) present in a cervical condyloma. When DNA from this isolate was hybridized at high stringency with HPV types 1 through 50 (HPV-1 through HPV-50), it showed weak homology with HPV-6 and -16 and stronger homology with HPV-26. A detailed restriction endonuclease map was prepared which showed marked differences from the maps for other HPVs that have been isolated from the female genital tract. Reassociation kinetic analysis revealed that HPV-26 and this new isolate were less than 10% homologous; hence, the new isolate is a novel strain of HPV. The approximate positions of the open reading frames of the new strain were surmised by hybridization with probes derived from individual open reading frames of HPV-16. In an analysis of 175 genital biopsies from patients with abnormal Papanicolaou smears, sequences hybridizing under highly stringent conditions to probes from this novel HPV type were found in 4.2, 6.1, and 2.4% of biopsies containing normal squamous epithelium, condylomata, and intraepithelial neoplasia, respectively. In addition, sequences homologous to probes from this novel isolate were detected in one of five cervical carcinomas examined.

Adult↗

A comparison of biotin and isotope-labeled ribonucleic acid probes for in situ detection of HPV-16 ribonucleic acid in genital precancers.

Genital precancers were analyzed by in situ hybridization for the presence of HPV RNA using single-stranded RNA probes. To compare the sensitivity of biotin- and 35S-labeled probes, serial sections from three biopsies containing variable amounts of HPV 16 RNA were analyzed with probes containing each label. The probe template was a cloned fragment of the HPV 16 genome spanning portions of the E2, E5 and L2 orf's. When a focus contained a strong hybridization signal with 35S-labeled probes (i.e., target/background ratio greater than 40) serial sections of the same area usually demonstrated a strongly positive signal with biotin-labeled probes. When the signal with 35S in a given focus was weak (target/background ratio less than 20), serial sections contained either a very weak or no detectable signal with the biotinylated probe. From this study it appears than 35S-labeled RNA probes exceed the sensitivity of biotin-labeled probes by nearly an order of magnitude with short exposures (4 days), and with longer exposures (1 to 2 weeks), approach the sensitivity of that reported for tritiated probes and exposures of 1 month or longer.

Biotin↗

Histologic correlates of papillomavirus infection of the vagina.

Vaginal warts (condylomata) secondary to human papillomavirus (HPV) infection are most easily identified when perinuclear halos are seen with clear-cut nuclear atypia (koilocytotic atypia) in the superficial cells of the lesion. However, vaginal lesions clinically resembling condylomata may exhibit lesser degrees of nuclear atypia with findings suggestive of, but not typical for, the presence of HPV. The diagnosis and management of such lesions are unclear. We correlated histologic findings with the detection of HPV DNA sequences in 39 vaginal lesions that contained a spectrum of clinical and histologic features suggestive of, or diagnostic for, condyloma. We detected HPV DNA in 63% (N = 22) of lesions with koilocytotic atypia and in 11.7% (N = 17) of lesions that showed some histologic features suggesting condyloma but that lacked koilocytotic atypia. These findings imply that vaginal lesions lacking koilocytotic atypia are not always caused by HPV, emphasizing the need for a conservative approach when the diagnosis of vaginal condyloma is not clear-cut.

Adult↗

Involucrin expression in cervical intraepithelial neoplasia: a critical evaluation.

Involucrin is a keratinocyte envelope protein precursor which is synthesized at an early stage of differentiation in normal squamous epithelium. Recent studies suggest that this protein may be a marker for neoplastic epithelium. To address this issue, we analyzed involucrin expression in 105 biopsies containing 119 areas of normal, condylomatous, and neoplastic epithelium. Overall, 88, 75, and 55% of condylomata, well-differentiated CIN, and poorly differentiated CIN (carcinoma in situ) contained positive staining for involucrin. Excluding lesions with severe inflammation, 100, 88, and 55% of these lesions, respectively, were positive. Staining patterns in neoplastic lesions differed from those in the normal epithelium and condylomata; the staining in CIN tended to be focal, and intensity of staining varied widely from cell to cell in all layers of the epithelium. In high grade CIN, staining correlated with increases in cell size and cytoplasmic differentiation. These studies suggest that involucrin will not differentiate between lesions of low versus high risk for progressing to invasive carcinoma. However, the patterns of involucrin expression confirm the marked differences in patterns of cellular differentiation between classical condylomata and CIN.

Condylomata Acuminata↗

Colposcopic correlates of cervical papillomavirus infection.

We compared the colposcopic and histologic features of 39 papillomavirus-related cervical lesions with their associated human papillomavirus type. Two thirds of the lesions contained human papillomavirus type 16-related deoxyribonucleic acid, and 69% of them were classified as cervical intraepithelial neoplasia I or II, in contrast to 92% of lesions containing human papillomavirus 6/11 deoxyribonucleic acid. On histologic examination, low-grade cervical intraepithelial neoplastic lesions tended to be sharply demarcated and have an uneven or granular surface contour. In contrast, high-grade lesions often had diffuse borders and were usually smooth in appearance. Both low- and high-grade lesions displayed variable degrees of whiteness, thickness, and papillomatous configurations. Patterns of coarse punctuation were more common in higher grade cervical intraepithelial neoplastic lesions and in those containing human papillomavirus 16. Predictably, the colposcopic features of lesions containing human papillomavirus 6/11 deoxyribonucleic acid sequences compared closely with those of low-grade cervical intraepithelial neoplasia. In contrast, human papillomavirus 16-associated cervical intraepithelial neoplasia exhibited a greater spectrum of colposcopic patterns, including those associated with condyloma and low- and high-grade cervical intraepithelial neoplastic lesions. We conclude that, although a portion of low- and high-grade cervical intraepithelial neoplastic lesions can be distinguished colposcopically, a significant number of lesions containing features of low-grade cervical intraepithelial neoplasia or condyloma contain human papillomavirus 16 deoxyribonucleic acid and cannot be distinguished from presumably innocuous human papillomavirus infections.

Adult↗

Detection of papillomavirus nucleic acids in genital precancers with the in situ hybridization technique.

Recent advances in in situ hybridization technology have made it possible to analyze the distribution of human papillomavirus (HPV) type 16 nucleic acid sequences in genital neoplasms. This review addresses the methodology of in situ hybridization as it relates to the detection of HPV sequences in precancerous lesions and explores the potential value of this technique for both detecting HPV sequences in tissue sections and analyzing HPV gene functions that may be important in the genesis of squamous neoplasia.

DNA, Viral↗

Chlamydia trachomatis infection of the female genital tract. Pathogenetic and clinicopathologic correlations.

Further studies are needed to define the clinicopathologic manifestations of CT infection. Many questions remain regarding the natural history and pathogenetic mechanisms of CT and its biologic and clinical interactions with other prevalent STDs. However, it is apparent that CT is a major cause of STD in the Western world and that its incidence and prevalence have increased to epidemic proportions in young, sexually active women and men. As with other STDs, epidemiologic control of CT infection is of paramount importance. The clinician and pathologist should develop a heightened awareness of the probability of Chlamydia infection in all patients at risk for STD, and in clinical settings, only a high index of suspicion will result in timely therapeutic intervention. Although more simplified and less expensive diagnostic procedures for CT are being investigated, presently, culture isolation is the best and most accurate diagnostic method for CT genital infection and its use should be popularized and made more easily available. Immunofluorescent staining using monoclonal and heterologous antibodies to extracellular CT elementary bodies in preselected smears appears promising as a diagnostic technique and requires further study. There is no apparent role for the use of routine cyto- and histologic microscopy in the diagnosis of CT infection and the practice of diagnosing presumed chlamydial vacuoles or inclusions from cervicovaginal Pap smears should be actively discouraged. Although CT cervicitis plays a dominant role in the pathogenesis and dissemination of CT infections, it should be remembered that multiple sites of genital involvement occur commonly with CT infection and this multifocality should be considered when CT cervical cultures are negative and in post-treatment follow-up. Cultures should be obtained from sites of suspected involvement and should include scrapings or biopsy sampling of the tissue surface to insure the presence of sufficient numbers of epithelial cells. Local secretions or exudate should not be considered adequate. In the female, sampling of the urethra, rectum, and endometrium may facilitate accurate diagnosis. Scraping or sampling of the tubal epithelium by biopsy may provide diagnostic material in acute salpingitis and PID and should be considered if laparoscopy or laparotomy are performed. Routine screening by culture for CT cervicitis has been suggested in high-risk clinical groups and in antepartum patients for prophylaxis of fetal and neonatal disease and requires serious consideration because of the high prevalence of CT infection.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Bowenoid papulosis in three-year-old girl.

A three-year-old girl presented with perianal bowenoid papulosis that was presumed to be induced by sexual contact. The lesion was treated by biopsy only and regressed over 8 months without further therapy. The importance of this case with respect to the viral cause, venereal transmission, and spontaneous regression is discussed. This case represents the youngest known patient with bowenoid papulosis reported to date.

Adolescent↗

In situ hybridization analysis of HPV 16 DNA sequences in early cervical neoplasia.

The authors examined 18 cervical intraepithelial neoplasms (CIN) for the presence of human papillomavirus (HPV) DNA sequences by Southern blot hybridization and DNA-DNA in situ hybridizations for HPV DNA sequences and compared the epithelial distribution of HPV 16 DNA sequences with HPV 6/11 sequences in selected condylomas. Fifteen of the 18 CIN lesions contained HPV 16 DNA as determined by Southern blot hybridization. With the use of biotinylated HPV 16 DNA probes, 10 of the 18 were positive by in situ hybridization, 9 of which were also positive by Southern blot hybridization. In situ hybridization to HPV 16 probes was found primarily in areas of CIN which contained either maturation or koilocytotic atypia, although in two cases hybridizing sequences were detected in superficial cells from epithelium with no discernible maturation. Staining in both condylomas and CIN lesions varied in distribution and intensity. However, in some CIN lesions staining from cell to cell varied considerably. This greater variability in staining appeared to correlate with greater morphologic variations which characterize CIN, and which may influence greater variation in HPV DNA replication. Thus, some differences in patterns of hybridization for HPV DNA between CIN and condylomas may be explained by morphologic differences in the two classes of lesions. Differences in viral gene expression between condylomas and CIN and their relationship to morphologic findings remain to be clarified.

Base Sequence↗

Human papillomavirus type 16 infection: a morphological spectrum with evidence for late gene expression.

Human papillomavirus (HPV) type 16 is a unique strain found almost exclusively in squamous precancerous lesions and invasive carcinomas of the genital tract. A histological and immunohistochemical analysis of 34 cervical biopsies from which HPV 16 was isolated was performed to determine: the morphological spectrum of HPV 16 "infection" and if HPV late genes were expressed in lesions containing this virus. Twenty-eight of thirty-four (82%) biopsy specimens contained areas fulfilling the histological criteria for cervical intraepithelial neoplasia (CIN) (defined as the presence of abnormal mitoses and/or diffuse nuclear atypia in a portion of the biopsy). However, 19 of 28 (68%) CIN lesions also contained focal areas of epithelium indistinguishable from condylomata. Three biopsy specimens each contained condyloma only and normal-appearing squamous epithelium. Three of thirty-one lesions (10%) showed evidence of HPV capsid antigens. The presence of areas of condyloma, as well as capsid antigens, indicates that lesions containing HPV 16 share certain similarities with conventional warts associated with other HPVs. Furthermore, the wide range of morphology in lesions containing HPV 16 suggests that histological or cytological recognition of HPV 16-associated CIN lesions may not always be possible.

Carcinoma in Situ↗

Latent papillomavirus and recurring genital warts.

After anogenital condylomata and intraepithelial neoplasms are removed, they frequently recur. Since these lesions are related to papillomaviruses, it has been suggested that latent papillomavirus infection is responsible for recurrence. We studied 20 cases of anogenital lesions that were treated by laser therapy and analyzed biopsy specimens of margins of normal skin adjacent to the lesions for papillomavirus sequences by Southern blot hybridization. In nine cases (45 per cent), papillomavirus sequences were detected in the normal skin margin; lesions recurred in 6 of the 9 patients (67 per cent), in contrast to only 1 of 11 patients (9 per cent) whose margins were negative for the presence of papillomavirus sequences. All but one recurrence developed within 15 mm of the treatment area. Our results demonstrate that clinically and histologically latent papillomavirus exists beyond the treatment area and that its presence influences subsequent recurrences.

Animals↗

Immunoperoxidase localization of chlamydial antigens in acute salpingitis.

Seventy surgically excised fallopian tubes in which there was originally a diagnosis of acute salpingitis were reviewed histologically and screened for chlamydial antigens by the immunoperoxidase technique. Chlamydial antigens were localized within tubal epithelial cells in two of the 70 cases (3%). Endometrial specimens from these two patients were also positive for chlamydial antigens. There was no definite correlation between the histologic features of the salpingitis and chlamydial immunoperoxidase positivity.

Acute Disease↗

Human papillomavirus infection of the esophagus. A clinicopathologic study with demonstration of papillomavirus antigen by the immunoperoxidase technique.

Papillomaviruses are known to be oncogenic in animals. In humans they are associated with benign squamous tumors (verruca, condylomata acuminata, and papillomas) in a variety of body sites. Human papillomavirus (HPV) infection of the esophagus, however, has not previously been documented. Recent reports of condylomatous changes in esophageal epithelium adjacent to esophageal carcinoma and the sporadic descriptions of esophageal papillomas in the literature for many years, lend credence to the assumption that HPV may affect the squamous mucous membrane of the esophagus. In the current study 75 cases, including 2 papillomas and 73 focal epithelial hyperplasia of the esophagus, were examined for histologic evidence of HPV infection as characterized by the presence of koilocytosis, giant and multinucleated cells, dyskeratosis, hyperkeratosis, acanthosis, papillomatosis, and anisonucleosis. Thirteen of the cases--the 2 papillomas and 11 of the focal epithelial hyperplasias--contained distinctive histologic evidence of HPV infection. The presence of HPV antigens was demonstrated by immunoperoxidase (IMPO) in the 4 of the 13 cases (31%). In the remaining cases the IMPO was equivocal in two and negative in seven.

Adult↗