Human papillomavirus testing in primary cervical screening.
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DNA, Viral↗
Biomedical subjects
R M Richart
Publications and source records attributed to R M Richart.
Evaluation of the Hybrid Capture human papillomavirus deoxyribonucleic acid detection test.
OBJECTIVE: Our purpose was to evaluate the sensitivity and accuracy of a new, nonradioactive human papillomavirus deoxyribonucleic acid detection method. STUDY DESIGN: Cervical samples from 520 women were assayed for human papillomavirus deoxyribonucleic acid with both the Hybrid Capture test and polymerase chain reaction. RESULTS: Human papillomavirus deoxyribonucleic acid was detected with Hybrid Capture in 106 (42%) of 254 samples from women with no evidence of cervical intraepithelial neoplasia and 211 (79%) of 266 with cervical intraepithelial lesions or cervical cancer. There was a good correlation between Hybrid Capture and polymerase chain reaction. Hybrid Capture correctly identified 92% of samples found to contain a human papillomavirus type with a high or intermediate oncogenic risk with polymerase chain reaction. Although Hybrid Capture can quantify the amount of human papillomavirus deoxyribonucleic acid present in a sample, no correlation was observed between the relative amount of human papillomavirus deoxyribonucleic acid detected with Hybrid Capture and the grade of cervical lesion. CONCLUSION: The Hybrid Capture test is a sensitive and accurate method for identifying human papillomavirus types of high and intermediate oncogenic risk in clinical specimens.
Cervix Uteri↗
A polymerase chain reaction-enzyme-linked immunosorbent assay method for detecting human papillomavirus in cervical carcinomas and high-grade cervical cancer precursors.
OBJECTIVE: To develop and evaluate a novel polymerase chain reaction (PCR)-enzyme-linked immunosorbent assay (ELISA)-based method for detecting high-oncogenic-risk human papillomaviruses (HPV). METHODS: An HPV assay based on PCR amplification of a region of the E6 open reading frame and ELISA detection of PCR products that specifically identify high-oncogenic-risk HPV types (eg, types 16, 18, 31, 33, 35, 39, 45, 56, 58, and 65) was developed. Dacron swabs were used to obtain samples from the cervices of 371 women referred for colposcopy. The swabs were analyzed using the PCR-ELISA method. The results of HPV DNA testing were then compared with the results of a repeat Papanicolaou smear and cervical biopsy obtained at the same visit. RESULTS: The sensitivity of the PCR-ELISA HPV test for detecting invasive cervical cancer or high-grade squamous intraepithelial lesions (SIL) was 90%. High-oncogenic-risk HPVs were detected in six of seven women with biopsy-confirmed invasive cervical cancer, 74 of 81 women with biopsy-confirmed high-grade SIL, 58 of 128 women with biopsy-confirmed low-grade SIL, and 46 of 155 women with no evidence of cervical disease by colposcopy and cervical biopsy. When used in conjunction with a repeat Papanicolaou test, 97% of the women with invasive cervical carcinoma and high-grade SIL lesions were identified. CONCLUSION: The PCR-ELISA-based HPV detection provides the potential for an automated, rapid, and sensitive test for cervical cancer and high-grade cervical lesions.
Base Sequence↗
Loop excision of the uterine cervix.
Over the past three years, loop excision has become a standard form of therapy for cervical intraepithelial neoplasia. Clinical trials have found loop excision to be faster and easier than laser ablation for treating cervical intraepithelial neoplasia and to have similar complication and success rates. In addition, loop excision produces a specimen that is suitable for histopathologic evaluation in the majority of patients. As our clinical experience with loop excision has increased, little impact on fertility and pregnancy outcome has been found, but there continues to be concern about overuse of the technique as a method of evaluating women with low-grade abnormal Papanicolaou smears.
Cervix Uteri↗
Cervical intraepithelial neoplasia in women infected with the human immunodeficiency virus: outcome after loop electrosurgical excision.
Our clinical experience with loop electrosurgical excision as therapy for cervical intraepithelial neoplasia (CIN) in women infected with human immunodeficiency virus is described. Information for this analysis was obtained from a retrospective chart review of all women with biopsy-confirmed CIN treated by loop electrosurgical excision who attended our colposcopy clinic during January 1991 to September 1992. Outcomes in women known to be HIV-seropositive were compared to those in women of unknown HIV serostatus. Patients included in the analysis were followed for at least 6 months or until the documentation of recurrent/persistent CIN, and all had at least one post-treatment colposcopic examination, including endocervical curettage and cervical biopsy of any acetowhite lesions. Recurrent/persistent CIN following loop excision was documented in 56% (19 of 34) HIV-infected women compared with 13% (10 of 80) women of unknown serostatus (OR 8.9, P < 0.001). HIV-infected women had a significantly higher rate of recurrent/persistent CIN than women of unknown serostatus, regardless of grade of CIN. In HIV-infected women, recurrent/persistent CIN following loop excision developed in 20% (1 of 5) with CD4+ T-lymphocyte counts > 500 cells/microliters compared to 61% (11 of 18) with CD4+ counts < or = 500 cells/microliters (P = 0.13). Loop electrosurgical excision has a high failure rate in HIV-infected women, and this failure rate may increase as the level of immunosuppression increases.
Adult↗
Relationship of human papillomavirus type to grade of cervical intraepithelial neoplasia.
OBJECTIVE--To determine the relationship of human papillomavirus (HPV) type to grade of cervical intraepithelial neoplasia (CIN) in a large series of cases. DESIGN--A survey of HPV types in CIN lesions detected using a new, highly accurate method for typing HPV that is based on restriction fragment length polymorphism analysis of amplimers produced during polymerase chain amplification of the conserved L1 region of HPV using consensus primers. SETTING--Private gynecologists' offices and inner-city colposcopy clinics. PATIENTS--A convenience sample of 276 HPV DNA-positive cervical biopsy specimens or samples from patients undergoing colposcopy for abnormal Papanicolaou smears. INTERVENTION--None. MAIN OUTCOME MEASURE(S)--Human papillomavirus type(s). RESULTS--Cervical intraepithelial neoplasia 1 lesions were relatively heterogeneous with regard to associated HPV types. Nineteen percent of CIN 1 lesions were associated with HPV types 6 or 11; 29% contained HPV types 16, 18, or 33; and 19% were associated with "novel types" of HPV. It was also found that 22% of CIN 1 lesions were associated with more than one HPV type. In contrast to CIN 1, both CIN 2 and CIN 3 were relatively homogeneous with regard to associated HPV types. Eighty-eight percent of CIN 2 and 3 lesions contained HPV types 16, 18, or 33. Unlike CIN 1 lesions, which often contained multiple types of HPV, only 7% of CIN 2 and 3 lesions were associated with multiple HPV types. CONCLUSIONS--Cervical intraepithelial neoplasia should be classified into two separate categories--low-grade and high-grade CIN. Since only 29% of low-grade lesions are associated with HPV types 16, 18, or 33, HPV type could potentially play a role in determining the most appropriate clinical management of patients with low-grade CIN. However, prospective follow-up studies of lesional behavior based on HPV type are required before clinical recommendations can be made.
DNA, Viral↗
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)
Adolescent↗
Comparison of specimens removed by CO2 laser conization and the loop electrosurgical excision procedure.
A comparison is made of the histologic changes in the cervical epithelium and stroma following CO2 laser conization and office excisional biopsy of cervical tissue using the loop electrosurgical excision procedure. In both types of specimens, two zones of thermal injury were detected. The zone at the margin of resection measured approximately 50 microns in thickness and was characterized by extensive carbonization and charring. The other zone was much more variable in thickness and characterized by tissue coagulation, but lacked charring. No significant difference in the biocharacteristics or extent of thermal damage was detected between the methods. For 11 specimens obtained with the CO2 laser, the coagulated zone ranged from 130-750 microns in greatest thickness; the mean thickness was 411 microns. For 40 specimens obtained using the loop procedure, the range of thickness of the coagulated zone was 150-830 microns, and the mean thickness was 396 microns. The difference in the mean value of thermal injury (measured in microns) between the laser and loop procedures was not significant (Student t test; P = .79). Extensive areas of carbonization and epithelial distortion at the margins of excision were only occasionally present in specimens obtained by the electrosurgical excision procedure but almost invariably present in CO2 laser specimens. However, in all cases it was possible to evaluate the epithelium and the stroma both histologically and cytologically.
Carbon Dioxide↗
Treatment of cervical intraepithelial neoplasia using the loop electrosurgical excision procedure.
In selected patients with cervical intraepithelial neoplasia (CIN), outpatient ablative procedures represent a readily accepted and highly effective treatment modality. The recently introduced loop electrosurgical excision procedure offers a quick and simple alternative to cryotherapy and laser ablation for treating CIN, and has the distinct advantage of allowing both diagnosis and treatment of selected patients at a single visit. This report presents our clinical experience treating 432 patients with CIN using the loop electrosurgical excision procedure on an outpatient basis. Small loop electrodes were used to excise CIN lesions in 275 patients, and large loop electrodes were used in 157. When performed on an outpatient basis under local anesthesia, loop excision was well tolerated by patients with only minimal discomfort. Post-treatment bleeding occurred in less than 2% of the subjects and responded to either recauterization or packing of the cervix. Post-treatment stenosis occurred in less than 1%. The success rate of the loop electrosurgical excision procedure, as defined by absence of cytologic, histologic, or colposcopic lesions 4-48 months after therapy, was 80% for women treated using the small loop electrodes. Ninety percent of all patients treated using the large loop electrodes were free of disease during 6-12 months of follow-up. For women being treated for primary (as opposed to recurrent) disease, the success rate with large loop electrodes was 94%.
Carcinoma in Situ↗
Pathology of the cervix.
Over the last year, the majority of research on the pathology of the cervix has been focused on the human papillomavirus (HPV) and its role in the pathogenesis of cervical neoplasia. Several major points emerged from these studies. First, the incidence of latent HPV infection in the general population is greater than previously thought. Up to 31% of a college-aged population has HPV DNA detected in cervical swabs. Second, in situ hybridization to detect HPV has been found to be a useful quality control measure for laboratories diagnosing cervical lesions. Finally, it is now recognized that many different HPV types can infect the cervix and be associated with cervical neoplasia. With regard to treatment, the introduction of loop electrosurgical excision procedures for treating cervical intraepithelial neoplasia lesions promises to have a significant impact on the management of cervical disease.
Female↗
Pearly penile papules: absence of human papillomavirus DNA by the polymerase chain reaction.
Pearly penile papules clinically resemble the sexually transmitted papular variant of genital condylomata. Histologically, however, pearly penile papules consist of fibropapillomata that lack the characteristic morphologic features of human papillomavirus (HPV) infection. To study the possible association of HPV infections with pearly penile papules, we examined tissue specimens from 13 men with pearly penile papules with and without associated penile condylomata. Biopsy specimens were tested for the presence of HPV DNA by the polymerase chain reaction. None of the pearly penile papules contained HPV DNA sequences, whereas four of seven cases clinically suspected of being condylomata associated with pearly penile papules contained HPV DNA. These results confirm that pearly penile papule lesions do not contain HPV DNA; therefore, the distinction between pearly penile papules and penile condylomata is clinically significant.
Adult↗
Carbon dioxide laser energy disperses human papillomavirus deoxyribonucleic acid onto treatment fields.
The possibility of dispersing viral deoxyribonucleic acid during carbon dioxide laser treatment of human papillomavirus-containing genital infections has been investigated with a commercially available dot blot hybridization technique. The viral ribonucleic acid probes were specific for groups of human papillomavirus types 6/11, 16/18, and 31/33/35. Laser energy was delivered by continuous-wave mode and the plume of smoke was evacuated by a vacuum suction system. Samples were taken with Dacron swabs from lesional tissues of 43 patients as well as from the treated areas and from the 5 cm surrounding normal skin before and after laser vaporization. Human papillomavirus deoxyribonucleic acid was identified in swabs from 34 of 43 (79%) lesional tissues and 7 of 43 (16%) treatment fields. Although a trend for higher human papillomavirus deoxyribonucleic acid positivity in laser margins after therapy (7/43, 16%) than before (4/43, 9%) was observed, the rates were not statistically significant. It is concluded that carbon dioxide laser energy disperses human papillomavirus deoxyribonucleic acid onto treatment fields and the adjacent normal epithelium. Viral contamination of treated areas may be reduced by positioning the fume evacuator within 1 cm of the field of laser vaporization and cleaning the treated areas and surrounding tissue after therapy.
Adolescent↗
Case-control study of in situ and invasive carcinoma of the vagina.
A case-control study of 41 patients with carcinoma in situ (CIS) or invasive cancer of the vagina and 97 community controls was undertaken to identify potential risk factors. Although vaginal and cervical cancers often occur as multiple primaries, only a few common risk factors prevailed. Similar to cervical cancer, low education and family income were risk factors for vaginal CIS and invasive cancer. In addition, history of genital warts was strongly related (RR = 2.9), although other sexual factors were not. Previous genital abnormalities related to subsequent cancer risk, with significant associations seen for vaginal discharge or irritation (RR = 6.1), a previous abnormal Pap smear (RR = 3.8), or an early hysterectomy (RR = 6.7). In addition, there was some evidence that vaginal trauma might be involved, with nonsignificant and independent associations relating to regular douching with preparations other than water or vinegar (RR = 2.7) and frequent washing of the genital area (RR = 2.7). Further studies are needed to determine whether our findings persist among a larger series of cases.
Adult↗
In situ hybridization analysis of human papillomavirus DNA segregation patterns in lesions of the female genital tract.
Various histologic features may be used to divide human papillomavirus (HPV)-related lesions of the genital tract into two groups: condylomata and "low-grade" or grade 1 cervical intraepithelial neoplasias (CIN 1) versus "high-grade" or grade 2 and 3 intraepithelial neoplasias. Using in situ hybridization analysis we correlated HPV DNA type with histologic features in 350 biopsies of lesions from the cervix, vulva, and perianal region. HPV DNA was most commonly found in vulvar and perianal condylomata (39/46, 85%), whereas the rate in CIN 1 lesions was 72% (86/120). The rates were 53% (40/76) and 57% (12/21) in CIN 2/3 and vulvar intraepithelial neoplasm (VIN) grades 2 and 3, respectively. The HPV type in all but 2 of the 39 perianal and vulvar condylomata which contained HPV was 6/11. Despite their similar histologic features, the HPV type in only 23 of 86 (27%) CIN 1 cases with detectable HPV was 6/11 compared to 31 of 86 (36%) which contained HPV 16-related DNA and 32 of 86 (37%) which contained HPV 31,-33, or -35-related DNA. The viral DNA in the majority of CIN 2/3 lesions and all of the VIN 2/3 lesions was HPV-16 related; no CIN 2/3 or VIN 2/3 lesion had HPV 6/11-related DNA. It is concluded that although cutaneous genital tract condylomata are highly associated with HPVs of low oncogenic potential (types 6 and 11), these HPV types are not as frequent as the oncogenic HPVs (16, 31, 33, and 35) in CIN 1 lesions. Further, HPV 6/11 appears to be very rarely associated with CIN 2/3 or VIN 2/3 lesions.
Condylomata Acuminata↗
Role of human papillomavirus in the pathogenesis of genital tract warts and cancer.
During the last decade a large number of clinical, epidemiological, and experimental studies have elucidated the role of HPV in the pathogenesis of anogenital cancer. Although the clinical and epidemiological studies have been criticized for a variety of technical and design shortcomings, for the most part they have independently reached the same conclusion--there is a strong association between the presence of specific types of HPV and the development of anogenital cancer. Similarly, laboratory studies clearly indicate that specific types of HPV act in concert with other cellular changes to transform a variety of cell types in vitro, including human cervical epithelial cells. Over the next decade the challenge is twofold. First we need to define precisely the mechanisms by which HPV either by itself or in concert with other factors, acts to transform anogenital epithelial cells. These studies will, it is hoped, identify important cofactors in the transformation process and determine the role of host immunity. Second, we need to determine the clinical applicability of the association between HPV and anogenital cancer. Large clinical studies will determine whether HPV testing of asymptomatic patients facilitates the detection of patients at risk for developing cervical cancer and whether the presence of a specific type of HPV in a cervical cancer actually affects a patient's prognosis. As the answers to these and other questions become available, we will be in a better position to assess the clinical importance of the associations between HPV and anogenital cancer.
Female↗
Human papillomavirus DNA in CO2 laser-generated plume of smoke and its consequences to the surgeon.
Carbon dioxide laser energy is absorbed by intracellular water but not by proteins or nucleic acids. The possibility of dispersing viral DNA during laser therapy of human papillomavirus (HPV)-containing genital infections was explored using a filter hybridization technique. Samples were taken using dacron swabs from 110 patients in nine separate treatment sessions as well as from five pre-filter canisters, four fume vacuum tubes, and from the nasopharynx, eyelids, and ears of the laser surgeon before and after laser surgery. The viral RNA probes were specific for groups of HPV types 6/11, 16/18, and 31/33/35. Human papillomavirus DNA was identified in swabs from 65 of 110 (60%) of histologically unequivocal condylomata and cervical intraepithelial neoplasias. One of the five pre-filter canisters (20%) tested was HPV DNA-positive after laser treatment of 65 patients; it contained HPV DNA type 6. The four fume vacuum tubes tested in the remaining 45 patients were HPV DNA-negative, as were the nasopharynx, eyelids, and ears of the operator. Although HPV DNA may be released during laser vaporization of genital HPV infections, contamination of the operator is unlikely provided appropriate equipment for evacuating HPV DNA-positive smoke is used.
Adolescent↗
Human papillomavirus DNA in situ hybridization may be used for the quality control of genital tract biopsies.
Biopsies of human papillomavirus (HPV)-related lesions of the lower female genital tract were studied using in situ hybridization for HPV DNA. The probes included HPV types 6, 11, 16, 18, 31, 33, 35, 41, 43, 44, 45, 51, 52, and 56. In cervical intraepithelial neoplasia (CIN) 1 lesions, 64 of 70 (91%) of formalin-fixed tissues were HPV DNA-positive; in vulvar condylomata, 34 of 36 (94%) were positive. Only two of 52 (4%) of the lesions diagnosed as equivocal for CIN 1 or condyloma were positive. Higher-grade CIN and vulvar intraepithelial neoplasia lesions had a lower rate of HPV DNA positivity. It is suggested that in situ hybridization may be used as a quality control procedure for the histologic diagnosis of HPV-related lesions.
DNA Probes, HPV↗
Micropapillomatosis labialis appears unrelated to human papillomavirus.
To clarify the hypothetical etiologic role of human papillomavirus (HPV) for micropapillomatosis labialis, the frequency of HPV infection was compared by dot blot hybridization techniques between vulvar samples from 34 women with micropapillomatosis labialis and 34 women with normal vulvar skin. Although more patients with micropapillomatosis labialis than controls had HPV DNA detected, this was not statistically significant (eight of 34 versus three of 34, respectively; and two of 23 versus one of 34, respectively, when only biopsies were analyzed). In a second part of the study, 22 patients with micropapillomatosis labialis were followed without treatment; the lesion regressed in 45% and persisted in 55% of the patients. Among 11 patients treated with CO2 laser, 5-fluorouracil, or trichloroacetic acid, the lesion persisted in three cases. These results suggest that these introital changes are unrelated to HPV and that a high percentage will regress without treatment.
Adolescent↗