Patricia J. McNicol

High prevalence of human papillomavirus in prostate tissues.

Specific human papillomavirus (HPV) types are associated with benign and malignant lesions of the anogenital region including the prostate gland. Using polymerase chain reaction (PCR) amplification of type-specific HPV sequences, we have assessed the prevalence of HPV DNA in prostate tissue from 88 individuals. Amplified sequences specific for HPV 16 were found in 34 of 56 benign prostatic hyperplasias and in 14 of 27 prostatic carcinomas. In contrast, HPV 18 was identified in only three benign hyperplasias and one carcinoma, all of which also contained HPV 16 DNA. Four of five normal prostates obtained at autopsy had no detectable HPV infection; one contained HPV 16 sequences. No significant difference in the prevalence of HPV DNA is observed between patients with benign disease and those with evidence of malignancy when fragments of surgical material are analyzed. Surgical method (transurethral resection or suprapubic prostatectomy) had no effect on the frequency of HPV detection. The prevalence of HPV DNA in the small number of normal prostates analyzed was not significantly different from that in the surgical samples. The presence of HPV in prostate tissues suggests a possible reservoir for sexual transmission of types with oncogenic potential. A role for the virus in the etiology of prostatic neoplasia remains to be demonstrated.

Vaginal microbial flora as a cofactor in the pathogenesis of uterine cervical intraepithelial neoplasia

The vaginal microbial flora of 106 women with histopathologically confirmed cervical intraepithelial neoplasia and 79 women without disease, was evaluated for Gardnerella vaginalis, Trichomonas vaginalis, Candida albicans and other yeasts. Flora morphology was assessed by gram staining of secretions. Cervical cultures were examined for Herpes Simplex virus, Cytomegalovirus and Neisseria gonorrhoeae. Chlamydia trachomatis antigens in cervical secretions were detected by enzyme immunoassay. Human Papillomavirus was identified by koilocytosis in cytologic or histopathologic specimens. Human Papillomavirus infection (P < 0.00001), vaginal infection with Mycoplasma hominis (P = 0.012) and abnormal vaginal flora (P = 0.006) were significantly associated with CIN, suggesting that CIN may be promoted by vaginal microorganisms in conjunction with human papillomavirus cervical infection.

Detection of Human Papillomavirus 16 Transcription in Human Prostate Tissue

Previously we demonstrated human papillomavirus type 16 DNA in a high proportion of benign hyperplastic (BPH) and cancerous (CaP) prostate specimens using the polymerase chain reaction (PCR). While these data designate the prostate as a possible reservoir for sexual transmission of HPV, an etiological role for the virus in prostatic neoplasia is uncertain. Since transcription of the E6/E7 genes of HPV 16 is essential for both viral replication and cellular transformation, we sought to assess the transcriptional activity of HPV 16 found in prostate tissues. The E6/E7 viral gene transcripts were identified in 5 of 10 BPH specimens and 3 of 7 CaP specimens known to contain HPV 16 DNA. Expression of the HPV viral genes is not associated preferentially with either BPH or CaP, nor is transcription observed in all samples which contain the viral genome. These findings suggest that the prostate may act as a site for HPV replication, but that HPV is unlikely to be involved in the transformation of prostatic cells.

Characterization of HPV-16 E6/E7 transcription in CaSki cells by quantitative PCR

Human papillomavirus (HPV) is associated with specific benign and malignant lesions of the epithelial and mucosal surfaces. Of the sexually transmitted types, HPV type 16 (HPV-16) is the most commonly associated with carcinoma of the uterine cervix. Expression of the E6/E7 open reading frame of the viral genome is considered critical in the development of neoplasia. Using the CaSki cervical carcinoma cell line as a model system, we have adapted the polymerase chain reaction to quantify the transcripts expressed from this region. It was found that 97.1% of the total spliced transcript is E6*I, which putatively encodes the E7 oncoprotein, while E6*II comprises 2.9% of spliced product. The ratio of E6*I to E6*II expression may be an important parameter in evaluating the disease risk associated with HPV-16 infection.

Human papillomavirus infection and the size and grade of cervical intraepithelial neoplastic lesions associated with failure of therapy

OBJECTIVE: This investigation was designed to identify specific risk factors associated with treatment failure for cervical intraepithelial neoplasia. METHOD: A cohort of 436 women was assessed for the presence of co‐factors associated with therapy failure. The risk factors included the HP V infection status of the patient, a previous history of genital condyloma and the size of cervical lesions. RESULT: The treatment outcome was not related to the treatment modality (P = 0.058). Thirteen (8.1%) women failed laser therapy while 15 (5.4%) women failed cryotherapy. While treatment failure occurred only in the presence of HP V infection (P = 0.036), failure was not related to infection by a specific genotype. Therapy failure was associated with treatment for CIN II (RR 4.157) and CIN III (RR 2.053) relative to CIN I and treatment of large lesions (P = 0.014). CONCLUSION: The determination of the relative area occupied by cervical lesions may have prognostic value in identifying women who are at risk for treatment failure.

Effect of the menstrual cycle on detection and typing of human papillomavirus in uterine cervical cells

We observe fluctuations in human papillomavirus detection and variation in genotyping between sequential cervical cell specimens analyzed by filter in situ hybridization. Furthermore, specimen adequacy for analysis varies. To determine whether these phenomena are correlated with menstrual cycle stage at the time of sampling, we analyzed cervical cell specimens from women with cervical intraepithelial neoplasia. Specimens were categorized on the basis of a 28-day menstrual cycle and were analyzed by hybridization to combined probes for virus types 6 and 11 or types 16 and 18. Specimen adequacy was determined by hybridization to a human Alu I repetitive deoxyribonucleic acid probe. Analysis of data with chi 2 revealed that fluctuations in virus detection and type variation are unrelated to menstrual cycle stage. Specimen adequacy is stage-dependent for women who take oral contraceptives. Whereas specimens can be collected at any time other than the first week of the menstrual cycle, accurate determination of infection status requires multiple assessments.

Laboratory diagnosis of latent human papillomavirus infection.

The etiologic association of human papillomavirus (HPV) with uterine cervical cancer has prompted the need for improved laboratory diagnosis of this virus. The application of conventional hybridization technology, including filter in situ hybridization (FISH) and Southern-blot analysis, has revealed that the detection and typing of the virus is inconsistent between sequential specimens from the same individual. To determine whether the polymerase chain reaction (PCR) can be used to provide a more accurate assessment of infection status, two exfoliated cervical cell specimens obtained sequentially from a cohort of 30 women without clinical evidence of cervical abnormalities were analyzed in parallel by FISH and PCR at 6-month intervals. Neither of the procedures provided consistent findings with two sequential specimens suggesting that multiple analyses are necessary to assess infection accurately. However, PCR was less subjective in interpretation and demonstrated greater specificity than did FISH. With the increased sensitivity inherent to PCR, our findings indicated that PCR is more likely to identify latent HPV infection with a single specimen.

Comparison of filter in situ deoxyribonucleic acid hybridization with cytologic, colposcopic, and histopathologic examination for detection of human papillomavirus infection in women with cervical intraepithelial neoplasia

human papillomavirus (HPV) infection is a disease of the entire female lower genital tract. Colposcopic examinations and biopsies of the cervix and vulva were performed on all patients. Two hundred two women had cervical disease, of whom 164 (81%) also had vulvar disease. The percentage was the same regardless of the severity of the cervical disease. One hundred ninety-four of the patients had vulvar disease and of these, 164 (85%) also had cervical disease. Twenty-nine of 37 women (78%) with overt vulvar condylomata had cervical disease; 15 of these presented without a Papanicolaou smear, and 13 had cervical disease. We conclude that HPV infection of the female lower genital tract is a multicentric disease. All patients with evidence of HPV infection should undergo colposcopic evaluation of the entire lower genital tract. The significance that this will have on future attempts to cure this infection needs to be studied.