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PubMed2006

Determination of HPV type 16 and 18 viral load in cervical smears of women referred to colposcopy.

It has been recognized that human papillomavirus infection is the major causal factor for high-grade cervical lesions. The aim of the study was to evaluate the relationship between HPV 16 and 18 viral loads and cervical status in different age strata. A duplex real time PCR method was devised to determine HPV 16 and 18 viral load per million of human cells using an in house plasmidic construct as a standard of quantification. The 151 cervical scrapes were collected before colposcopic examination from either abnormal cervico-vaginal smear (group 1, 97 patients) or from post treatment clinical follow-up (group 2, 54 patients). In women aged 30-40, the HPV16 viral loads were significantly higher in high-grade squamous intraepithelial lesion than in low-grade squamous intraepithelial lesion in both groups and HPV18 in group 1. In women aged 20-30 of group 1, high HPV viral load was associated in few cases with high-grade squamous intraepithelial lesion or low-grade squamous intraepithelial lesion, and surprisingly in some patients with normal cervix. HPV 16 and 18 viral loads are related to the severity of cervical lesion, and may be useful in the clinical management of cervical lesions. A specific follow-up may be useful for those with high viral load despite normal cervix.

Adolescent↗
PubMed2002

Photodynamic therapy of high-grade cervical intraepithelial neoplasia with 5-aminolevulinic acid.

BACKGROUND AND OBJECTIVES: To determine the safety and efficacy of 5-aminolevulinic acid (ALA) as a topically applied photosensitizer for photodynamic therapy (PDT) of cervical intraepithelial neoplasia (CIN). STUDY DESIGNS/MATERIALS AND METHODS: Forty women, who were at least 18 years old with persistent biopsy-proven CIN 2 and CIN 3 within the previous 3 months of enrollment, underwent PDT in a phase I and II design. Five escalating radiant energies (increments of 25 J/cm(2), beginning at 50-150 J/cm(2)) using a Coherent Dye Model 920 argon pumped dye laser providing light at 630 nm (maximum output 0.8 W) were used to perform PDT with a fixed dose of ALA (200 mg/ml). ALA was placed in a cervical cap fitted to the cervix. After 90 minutes, the cap was removed and the ectocervix was illuminated for 5-16 minutes, depending on the irradiance. Success was defined as the absence of CIN on Pap smear or colposcopic examination at 12-months. Patients were monitored for toxicity. RESULTS: Thirty-two women (80%) completed the study with 1 year of follow-up. Sixty percent had CIN 3 and 40% CIN 2. Success rates at 4, 8, and 12 months were 51, 46, and 31%, respectively, and were not light-dose dependent. Three patients progressed from CIN 2 to CIN 3. Toxicity was tolerable and only consisted of spotting, vaginal discharge, mild cramping, and vaginal warmth. There was no apparent dose relationship to toxicity. CONCLUSIONS: PDT at this light and ALA dose is well tolerated but has minimal activity in the treatment of CIN 2 and CIN 3. Other doses and schedules of light and ALA or novel photosensitizers may improve efficacy.

Adult↗
PubMed1984

CO2 laser conization versus conventional conization: a clinico-pathologic appraisal.

Two groups of patients recently underwent either laser or conventional conization at the University Women's Hospital in Bern, Switzerland. Of the total 49 patients treated, 25 underwent laser conization and 24 underwent conventional conization. All patients admitted to the study had cytologic, colposcopic, and/or histologic evidence for cervical intraepithelial neoplasia or chronic cervicitis resistant to conservative therapy. In the conventionally treated group, conization was performed with surgical scalpel, and hemostasis was achieved by Sturmdorff, Bonney, or Kraus sutures. In the laser-treated group, conization was performed by using the combination method of Dorsey and Grundsel. Blood loss was minimal in the laser-coned patients, compared to 119 ml blood loss in the conventionally coned patients. Hospitalization for the laser-treated group was 5.2 days in contrast to 7.0 days for the conventionally treated group. Postoperative bleeding and discharge were also considerably smaller or did not occur in the laser-treated group as compared to the conventionally treated group. With postoperative and long-term follow-up now under way, initial results indicate that laser conization, in comparison to conventional conization, also provides greater visibility of the squamocolumnar junction and a reduced incidence of cervical strictures. The results of this study suggest that the CO2 laser beam, properly and cautiously applied, is an efficacious surgical modality for the treatment of cervical preneoplastic disease.

Cervix Uteri↗
PubMed1985

CO2 laser vaporization for chronic cervicitis.

Chronic cervicitis is the most common disease occurring during the period of greatest sexual activity and reproductivity, and it is the most common gynecologic disease in young women. The disease is a common sequel to normal delivery and one of the main causes of infertility; it also may be precancerous. All the treated women in the present study exhibited preoperatively severe subjective symptoms for chronic cervicitis, and 32 out of 60 (53%) exhibited colposcopically atypical squamous epithelium. The women were examined 3, 6, and 12 months following laser surgery: 58 (97%) of them reported a decreasing intensity of their symptoms, and colposcopy revealed a normal postlaser transformation zone as well as a decreasing edema of cervical epithelium.

Adolescent↗
PubMed1987

Koilocytotic, virus-induced pre-neoplasia in women: a multifocal disease effectively treated with CO2-laser surgery.

A superficial koilocytotic lesion progressing to dysplasia and later into an aggressive invasive cervical cancer has been demonstrated. It is thought that these lesions create an area of susceptibility to neoplasia in the cervix, vagina, and in the vulva, and are defined as preneoplastic lesions. A total of 57 young women have been examined cytologically and colposcopically at least 3, 6, and 12 months following CO2-laser surgery. In 12 women (21%) the lesions were multifocal with the same histological pattern in the cervix and in the vagina and/or in the vulva. CO2-laser effectively eradicates the koilocytotic lesions in the cervix and in the vagina; in the vulva, however, relapses are common after an initial good effect. The diagnostic accuracy of cervicovaginal cytology was low: exfoliated koilocytotic cells were found in only 26.3% out of 57 cases with histologically proven koilocytotic lesion, even when the cytological smears were reexamined.

Adolescent↗
PubMed1990

Uterine cervical punch biopsy specimens can be analyzed by 1H MRS.

Biopsy specimens of the uterine cervix, including colposcopically directed punch biopsy specimens of females with atypical Papanicolaou smear tests, are suitable for analysis by magnetic resonance (MR) spectroscopy. A narrow lined lipid MR spectrum, characteristic of malignant tissue, is obtained from a 6-mm3 biopsy specimen of histologically confirmed squamous carcinoma of the cervix. In contrast, specimens containing inflammatory cells generate a broad component only centered at 1.3 ppm with a T2 relaxation value of less than 350 ms. Most biopsy specimens which contain dysplastic cells or evidence of human papilloma virus (HPV) infection have a discernible lipid spectrum similar to that of the malignant tissue specimen. Long T2 relaxation values found in malignant tissue specimens at 1.3 and 1.2 ppm are observed in some but not all of the biopsies which show evidence of HPV infection. The suitability of small tissue samples, such as punch biopsy specimens, for study by MR illustrates the sensitivity of this technique and its potential as an aid to histopathological discrimination between the various precursor states of cervical cancer.

Biopsy↗
PubMed2004

Preinvasive and invasive cervical cancer: an ex vivo proton magic angle spinning magnetic resonance spectroscopy study.

The aim of this study was to obtain (1)H MR spectra using magic angle spinning (MAS) techniques from punch biopsies (<20 mg) of preinvasive and invasive cervical disease and to correlate the spectral profiles with sample classification on the basis of histopathology. Tissue samples were obtained at colposcopic examination, during local treatment of cervical intraepithelial neoplasia (CIN) or at hysterectomy. (1)H MAS MRS was performed at 25 degrees C while spinning the sample at 4.5 kHz. After measurement, the tissue was immersed in formalin and the pathology determined. Histological examination after (1)H MAS MRS defined 27 samples with squamous cell carcinoma (SCC), 12 with CIN and 39 with only normal tissue. The standardized integrals of the lipid, choline and creatine regions of the spectra were significantly higher in SCC than in normal or CIN tissue. There was no obvious difference in the standardized integral of the region 4.15-3.5 ppm. The acyl fatty acid side-chain length was longer or less unsaturated in SCC than in normal tissue. Normal tissue from patients with SCC showed significantly higher triglycerides than normal tissue from patients with benign uterine disease but significantly lower triglycerides than SCC tissue. (1)H MAS MRS of the uterine cervix ex vivo may be used to differentiate non-invasive from invasive cervical lesions, increase interpretation of in vivo MRS and provide insights into tumor biology.

Adolescent↗
PubMed1988

Expression of the CD 15 antigen is a marker of cellular differentiation in cervical intra-epithelial neoplasia (CIN).

The CD 15 antigen (3-fucosyl N-acetyllactosamine), present on the outer cell membrane of cervical squamous epithelial cells, is recognized by the monoclonal antibody MC2, which is similar to several commercially available antibodies. Staining sections of cervical biopsies with MC2 clearly demonstrates the zone of supra-basal differentiated cells in the normal squamous epithelium. Staining with MC2 also demonstrates the diminished proportion of this zone occurring with grades of CIN, reflecting progressive de-differentiation of the epithelium. In immature squamous metaplastic epithelium, absence of cytoplasmic differentiation is reflected by lack of staining. As expression of the CD 15 antigen by cervical squamous cells mirrors cytoplasmic maturity and is a marker of cellular differentiation, staining colposcopic biopsies with MC2 may aid the routine histopathological grading of CIN. A comparison is made between the staining pattern observed using MC2 with that of two commercially available antibodies (Leu M1 and Dako M1), and a possible role for the CD 15 antigen in cellular adhesion in squamous mucosae is discussed.

Antibodies, Monoclonal↗
PubMed1994

Integrin expression in squamous neoplasia of the cervix.

Epithelial cell-basement membrane interactions are important in maintaining tissue architecture and function, and the anatomical and functional relationships between epithelial cells and their basement membranes are clearly altered in malignancy. These interactions are thought to be largely mediated by the integrins, a family of heterodimeric transmembrane glycoproteins, each consisting of an alpha and a beta chain. Epithelial integrins mainly belong to the beta 1 (VLA) subfamily, which forms receptors for matrix macromolecules such as fibronectin, laminin, and collagen. There is evidence that integrin expression changes in some epithelial malignancies, possibly in relation to invasive potential. Integrin expression in cervical neoplasia was studied by immunohistochemical examination of prospectively collected colposcopic biopsies. Well-characterized monoclonal antibodies against beta 1-4, alpha 1-6, and alpha V integrins were used to examine normal, koilocytic, and dysplastic cervical squamous epithelium, and invasive squamous carcinoma. beta 1, beta 4, alpha 2, alpha 3, alpha 6, and alpha V were expressed by the basal layer of normal cervical squamous epithelium and by dysplastic cells in CIN (cervical intraepithelial neoplasia) 1 and 2, with none being lost and no new chains acquired. In CIN3, these integrins were either expressed throughout the ectocervical epithelium or restricted to the basal layer. In the latter cases, integrin expression was retained to a greater degree by dysplastic squamous epithelium within endocervical glands. These patterns could not be correlated with age or smear history in the cases examined. Patterns of integrin expression in neoplastic cervical epithelium therefore differ from those of normal cervical epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Human papillomavirus typing in patients with Papanicolaou smears showing squamous atypia.

Three hundred sixty consecutive patients followed at the Massachusetts General Hospital Colposcopy Clinic had HPV typing performed from exfoliated cervical cells by a commercially available dot blot hybridization assay. This assay tests for three groups of HPV types: 6/11, 16/18, and 31/33/35. Of this group, 171 patients were referred because of a Papanicolaou (Pap) smear showing squamous atypia. Of the 171 patients referred for squamous atypia, 17 (10%) had histologic evidence of CIN. Thirty-three of the 171 (19%) had detectable HPV DNA, and 28 of the 33 had high-risk HPV types (16/18, 31/33/35). Of the 17 women with CIN, only 6 (35%) had high-risk types and 11 (65%) had no HPV DNA detected. Of the 28 women with atypia and high-risk HPV types, only 6 (21%) had CIN. This study demonstrates that commercially available HPV typing when used in patients with Pap smears showing squamous atypia is not clinically useful in identifying patients for colposcopic referral.

Carcinoma in Situ↗
PubMed1993

The case for conservative management of "incomplete excision" of CIN after laser conization.

Three hundred thirteen laser cone biopsies were performed for cervical intraepithelial neoplasia (CIN) over a 4-year period. The mean age of the patients was 39.9 years and average cytology follow-up was just under 3 years. Six patients defaulted colposcopic review and were excluded from analysis. Of the 75 cases with CIN extending to the endocervical resection margin, 9 (12%) were found to have residual disease. Only 2 (3.6%) of 56 cases with CIN extending to the ectocervical margin had residual CIN detected. In the 176 cases in which the CIN lesion was excised completely there have been no cases of residual CIN. The overall detection of residual disease was 3.6%. Further surgery in those cases with CIN extending to the resection margin is excessive. These patients should be managed conservatively with regular cytological follow-up.

Adult↗
PubMed1993

HPV, HIV infection, and risk of cervical intraepithelial neoplasia in former intravenous drug abusers.

The relation between human immunodeficiency virus (HIV), human papilloma virus (HPV) infection, sexual habits, reproductive history, and risk of cervical intraepithelial neoplasia (CIN) has been analyzed in a cross-sectional study conducted since 1986 among female former intravenous drug abusers attending for the first time to the Colposcopic Unit of the Ospedale Luigi Sacco of Milan and women consecutively admitted to the Community for Past Drug Abusers, S. Patrignano, Rimini. A total of 434 subjects entered the study; of those 128 (30%) had a diagnosis of CIN. Compared with HIV-negative subjects, odds ratio (OR) of CIN was 8.0 (95% confidence interval (CI) 4.6-14.1) for HIV-positive ones and the frequency of CIN 2 and 3 was higher in HIV-positive than that in HIV-negative subjects (chi 2(1), trend, 6.67, P 0.01). Compared with women without current HPV infection the OR estimate was 38.0 (95% CI 20.3-71.2) in those with current diagnosis of HPV infection. Considering HIV-positive subjects only, the frequency of CIN increased with stage of HIV infection and was higher in women with lower CD4+ values. Finally, no relation emerged between CIN risk and age, indicators of sexual habits, oral contraceptive use, parity, and history of spontaneous or induced abortions.

Adult↗
PubMed1994

Prospective randomized trial of LLETZ versus laser ablation in patients with cervical intraepithelial neoplasia.

Three hundred seventy-five patients with CIN on referral Pap and with a distinct cervical lesion on colposcopy were prospectively randomized to treatment with LLETZ or to standard colposcopic evaluation with directed cervical biopsies, endocervical curettage, and laser ablation of the transformation zone for biopsy proven CIN. Of the 195 patients that randomized to treatment with LLETZ, 32.5% had no evidence of dysplasia, 26.5% had CIN 1, 17.3% had CIN 2, 22.7% had CIN 3, and 0.5% had microinvasive carcinoma on final histologic evaluation. Of the 180 patients randomized to laser ablation, initial cervical biopsies demonstrated no evidence of dysplasia in 52.8% of patients, CIN 1 in 22.0%, CIN 2 in 18.3%, and CIN 3 in 5.7%. Only 114 (63.3%) of the women in the laser group required therapy. Complications were comparable for each treatment arm. Only 6.7% of patients randomized to LLETZ and 4.4% with laser ablation had persistent CIN on follow-up Pap. LLETZ appears to be effective, well tolerated, and less expensive, but the cost savings advantage of LLETZ over laser ablation may not apply to patients with CIN 1 on referral Pap smear since many do not require treatment.

Adolescent↗
PubMed1994

Large loop excision of the transformation zone (LLETZ): a pathologic evaluation.

Forty-six LLETZ cone biopsies were performed at the Medical College of Georgia from January 1991 through December 1991. All LLETZ cones were performed for diagnostic reasons following colposcopic biopsies. The majority of procedures were done by residents in obstetrics and gynecology with direct faculty supervision. All specimens were critically evaluated by one pathologist with regard to specimen orientation, thermal artifact, margins, histologic diagnosis, and overall specimen adequacy. The median number of specimens obtained per patient was two, with a maximum of eight. Sixteen patients had a separate endocervical specimen obtained. Thermal artifact was graded as slight in 16 cases, moderate in 18 cases, and severe in 12 cases. The transformation zone was identified in 33 cases. Margins were positive in 17 cases, negative in 21 cases, and nonevaluable in 8 cases. Only 13 LLETZ specimens were believed to compare in quality to a cold-knife cone biopsy. The main criticism about the specimens was the effect of thermal artifact on critical histologic evaluation. In three cases, the thermal artifact precluded an accurate enough evaluation to rule out microinvasion. Mucosa missing at the margins or inadequate representation of the transformation zone were major reasons to call a specimen inadequate. Endocervical specimens suffered the most thermal injury. Orientation of fragmented cone specimens present a problem in histologic evaluation. A major emphasis needs to be placed on the proper indications for LLETZ cone biopsy as well as education of practitioners and pathologists in proper specimen handling.

Artifacts↗
PubMed1994

Carcinoma of the cervix following conservative management of cervical intraepithelial neoplasia.

The purpose of this study was to identify the reasons for treatment failures in patients managed with cervical intraepithelial neoplasia who subsequently developed invasive carcinoma of the cervix. Of 672 patients seen with cervical carcinoma from 1980 to 1990 inclusive, at the Tom Baker Cancer Centre, 24 (3.6%) had previously undergone conservative treatment for CIN and represent the current study population. The initial colposcopic-guided biopsy showed metaplasia (2), CIN 2 (5), and CIN 3 (17). The conservative treatment methods included observation (5), electrocautery (1), laser ablation (3), surgical cone (5), and cryotherapy (10). The mean time interval in months from conservative treatment of CIN to diagnosis of cervical cancer was 21.8 with cryotherapy and 26.7 with laser ablation. The FIGO stage of invasive cervical cancer was Stage 1A (7), Stage 1B (15), Stage 2A (1), and Stage 3 (1). The single death was a patient aged 30 with metastatic small cell cervical carcinoma arising within 4 years of cryotherapy for CIN 3. Of the 24 patients, 13 were managed appropriately yet developed carcinoma, 3 deviated from an accepted standard colposcopy protocol, 5 had inadequate follow-up, 2 refused treatment, and 1 developed de novo disease. The principle reason for treatment failure according to the literature is blatant deviation from protocol. This study, however, suggests that established invasive disease may have gone undetected prior to an ablative therapy. Difficulties related to diagnosis are discussed. The importance of peer reviews becomes evident if practices are to be evaluated and changes to protocols are to be implemented.

Adult↗
PubMed1994

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↗
PubMed1995

Presurgical assessment and therapy of microinvasive carcinoma of the cervix.

Retrievable pathological specimens and clinical data on 70 patients with microinvasive carcinoma diagnosed on surgical specimens from cone biopsy or hysterectomy (Stage IA) were reviewed and compared to pertinent findings in the literature with the intent of evaluating diagnostic criteria and defining pathological features that may influence the outcome by therapy. Emphasis was given to the preoperative assessment emphasizing that both an accurate colposcopic evaluation and a detailed pathological analysis may reliably point to a conservative therapeutic approach. Increasing depth of stromal invasion was associated with lesion width as well as with endocervical extension, as measured on colposcopy, microcolpohisteroscopy, and histology. Lymph-vascular space involvement was significantly related to depth of invasion. Two patients of 28 with dissected nodes had node metastases as well as lymph-vascular space involvement. Both developed a pelvic recurrence. One had a > 1- to < or = 3-mm invasion depth, the other a > 3- to < or = 5-mm lesion invasion. While advocating a conservative procedure for Stage IA1, we suggest discrimination with regard to Stage IA2 because we believe that lymph-vascular involvement should be meticulously evaluated. In fact, > 1- to < or = 3-mm lesions without lymph-vascular space involvement can be conservatively treated, while for any other lesion falling within the Stage IA2 category a modified radical histerectomy plus pelvic lymphadenectomy should be recommended.

Adult↗
PubMed1995

Potential of cervical electrosurgical excision procedure for diagnosis and treatment of cervical intraepithelial neoplasia.

The aim of this study was to evaluate the diagnostic potential, treatment efficacy, specimen adequacy, and acute complication rate associated with electrosurgical excision procedure (EEP) of the cervix for the management of cervical intraepithelial neoplasia (CIN). Analysis was performed retrospectively on 153 consecutive patients who underwent EEP under colposcopic guidance. Patients with negative endocervical curettage (ECC), adequate colposcopy, and biopsy-proven CIN were considered candidates for therapeutic EEP, whereas patients with a positive ECC, inadequate colposcopy, or cytology two or more grades discordant from the biopsy results underwent diagnostic EEP. Histopathologic specimens were graded as adequate, suboptimal, or inadequate. Diagnostic EEP was performed in 85 cases, and the remaining 68 procedures were performed primarily for treatment. Specimens were graded as adequate in 83%, suboptimal in 13%, and inadequate in 4% of the diagnostic EEP's. Specimen adequacy correlated most strongly with operator experience (P < 0.05). Four patients were found to have microinvasive or invasive cervical carcinoma. Complications occurred in 7% of the EEPs performed. Most consisted of immediate or delayed hemorrhage. In conclusion, EEP is a safe, well-tolerated procedure which is acceptable as both a therapeutic and diagnostic tool in the management of CIN when performed by an experienced operator. We recommend that initial EEP procedures should be performed for therapeutic indications, since adequacy of EEP specimens correlated with the level of operator experience.

Adult↗