Abnormal Transformation Zone Research Articles

Predictors factors of the absence of high-grade intraepithelial lesion in excisional therapy specimen.

To identify predictive factors of the absence of high-grade intraepithelial lesion (HGSIL) in cervical excisional therapy specimen. Data from 835 women who underwent excisional therapy for a cervical intra epithelial lesion at the department of Gynaecology from two university hospitals, between January 2015 and December 2020 were reviewed. Demographic data, referral cytology, colposcopic findings, results of cervical biopsy and endocervical curettage were retrieved. Primary outcome was the absence of HGSIL on cervical excisional specimen analysis defined by the identification of no intraepithelial lesion or of low-grade lesion only. The absence of HGSIL on specimen was observed in 137 (16.4%) cases. Three factors were identified to have a significant and independent impact on the probability of the absence of HGSIL on specimen: age higher than 40 years (aOR: 1.8; 95%CI: 1.1-3.0; p=0.024), a small abnormal transformation zone (TZ) (aOR: 2.3; 95%CI: 1.4-3.7; p=0.001) and the result of the cervical biopsy at the time of colposcopic assessment not showing HGSIL (aOR: 8.6; 95%CI: 4.7-15.5; p < 0.001). No significant impact of the referral cytology nor of the colposcopic impression were observed. Although the result of cervical biopsy performed at the time of colposcopic assessment is the key risk factor for the absence of HGSIL on excisional specimen, age over 40 and a small abnormal TZ are the two other identified risk factors. Practitioners should consider these findings when deciding for excisional therapy.

HPV-related cervical disease and oropharyngeal cancer

Human papillomavirus (HPV), especially HPV 16, is associated with the development of both cervical and oral cancer. We show the case of a woman affected by HPV-related cervical disease and oropharyngeal squamous cell carcinoma (OPSCC). A 41-year-old woman arrived at our Colposcopy Center following an abnormal Pap smear result (ASC-H) and a diagnosis of moderate cervical dysplasia obtained by a cervical biopsy. She underwent a colposcopy that showed a cervical abnormal transformation zone grade 2. A laser conization was performed in November 2010. Histology reported a moderate/severe dysplasia. The cone resection margins were free. Follow-up colposcopy and cytology were negative. The HPV testing showed an infection by HPV 16. In October 2012, the patient presented to the Head-Neck ER after episodes of hemoptysis; a lesion was found in the left tonsillar lodge. A biopsy was performed with a result of squamous cell carcinoma with low-grade differentiation. The HPV testing detected a high-risk HPV and the immunohistochemical analysis was positive for p16. She was treated by chemotherapy and brachytherapy. She was followed at the head-neck center with monthly visits with oral visual inspection that showed complete absence of mucosal abnormalities. HPV-related OPSCC and cervical precancerous/cancerous lesions have significant similarities in terms of pathogenesis. They are both caused largely by HPV 16, as in the present case. In conclusion, because of this association found in literature and in our case, we think that women with HPV cervical lesions should have regular surveillance for oropharyngeal cancer, whereas women with OPSCC should be encouraged to have diligent cervical screening.

Human Papillomavirus Types Distribution in Eastern Sicilian Females with cervical lesions. A Correlation with Colposcopic and Histological Findings

To determine human papillomavirus (HPV) types distribution in cervical lesions in a Southern Italian female population in Messina and their relationship between HPV type and grade of colposcopic and histopathological abnormality, a total of 253 women aged 17-68years, with previous cytological abnormalities, were included in this study. HPV-DNA testing, colposcopy and biopsy were performed. For each sample, cervical cells were collected by centrifugation and DNA was extracted, followed by a PCR-based HPV-DNA assay and reverse dot blot genotyping. HPV-16 was found the most common type (46.6%) followed by HPV-31 (26.9%), -6 (18.6%), -58 (8.8%), -18 (6.7%), -66 (5.7%), -52 and -53 (4.7%). Out of 62 women with abnormal transformation zone (ATZ) area compatible with squamous intraepithelial lesion (SIL) or cervical cancer (CC), 64.5% was found high risk (HR) HPV-positive. Moreover the severity of the colposcopic diagnosis was positively correlated with the higher HPV oncogenicity risk (HPV-16 P = 0.023; and HPV-53 P = 0.047). The HPV-16 was found the most prevalent type within each histological category: 66.7%, 31.2%, 44% and 37.2% of CC, high grade (H)SIL, low grade (L)SIL and chronic cervicitis respectively; followed by HPV-31 present in 25%, 8%, and 13.3% of HSIL, LSIL and chronic cervicitis respectively. A higher HPV incidence than the rest of Italy was found, in agreement with that detected by other authors for the South of the country. These data provide further information about the types prevalence in women with cervical lesions living in Eastern Sicily, suggesting the introduction of new targeted vaccines against a wider spectrum of HPV.

Factors associated with psychological distress following colposcopy among women with low‐grade abnormal cervical cytology: a prospective study within the Trial Of Management of Borderline and Other Low‐grade Abnormal smears (TOMBOLA)

Little is known about psychological after-effects of colposcopy and associated investigations and treatment in women with low-grade abnormal cervical cytology. We investigated psychological distress following colposcopy and related procedures. Nine hundred and eighty-nine women aged 20-59 years with routine cytology showing low-grade abnormalities were recruited to the Trial of Management of Borderline and other Low-grade Abnormal smears and attended colposcopy. If the cervical transformation zone (TZ) was colposcopically abnormal, women had immediate loop excision or diagnostic punch biopsies, with treatment if these showed cervical intraepithelial neoplasia grade 2/3 (CIN2/3). Women completed socio-demographic and psychosocial questionnaires at recruitment and before colposcopy. Six weeks after their last procedure, women completed the Impact of Event Scale (IES). Logistic regression was used to determine factors associated with significant psychological distress (IES ≥ 9). Analyses were stratified by colposcopic impression. The response rate was 74%. Six weeks after the last procedure, 86 (21%) of 391 women with a normal TZ had significant distress compared with 144 (42%) of 337 with an abnormal TZ. In both groups, significant distress was associated with anxiety pre-colposcopy and pain or discharge afterwards. Additional variables predicting distress in women with a normal TZ were worries about having sex and dissatisfaction with support from others. In women with an abnormal TZ, additional predictors of distress were younger age, CIN2/3, bleeding following colposcopy and worries about having cancer. Substantial proportions of women experience psychological distress after colposcopy and related procedures, even when the colposcopy is normal. This is an important cost of cervical screening. Interventions to alleviate these adverse psychological effects are required.

Trial of management of borderline and other low-grade abnormal smears (TOMBOLA): Trial design

Cervical screening reduces the risk of cervical cancer by detecting and treating cervical intraepithelial neoplasia (CIN). The management of women with low-grade cervical abnormalities is controversial. Two management policies exist: repeat smears in primary care and colposcopy examination. It is not clear which of these is the more effective and efficient. There is also uncertainty as to the most effective and efficient management of women at colposcopy when an area of abnormality is seen on the cervix — immediate treatment or biopsy and selective recall for treatment if the biopsy result suggests this is necessary. The result of a human papillomavirus (HPV) test might assist in deciding the appropriate management of women with low-grade abnormalities. TOMBOLA, a pragmatic randomised-controlled trial set within the cervical screening programmes in Scotland and England, addresses these three areas of uncertainty. Almost four and a half thousand women aged 20–59 with a low-grade cervical abnormality have been recruited and randomised to either repeat smears or colposcopy examination. Women in the colposcopy arm of the trial are further randomised to a policy of either immediate treatment or biopsy and selective recall for treatment if they have an abnormal transformation zone. Women are followed up to an exit examination at 3 years. HPV testing is undertaken at recruitment and at the exit examination. The primary endpoint is cumulative incidence of CIN2/3. A range of other clinical, psychosocial and economic outcomes is being considered. This paper describes the design of the trial, and discusses the rationale underlying aspects of the design and the challenges faced in designing and implementing the trial.

Prospective Evaluation of Colposcopic Features in Predicting Cervical Intraepithelial Neoplasia: Degree of Acetowhite Change Most Important

The results of three coordinated studies using patients from community family practices and a university student health clinic in Ontario, Canada, between May 1995, and October 1998 were presented in this paper. Two randomized trials involved human papillomavirus (HPV) testing in women at least 17 years of age who were undergoing routine cytologic screening after an abnormal Pap smear. The third study was a cross-sectional trial of HPV testing in women 18 years of age and older with ASCUS (abnormal squamous cells of undetermined significance) who had been referred for colposcopic examination. The data presented are the results of colposcopic examination and directed biopsy in these patients. At colposcopy, 5% acetic acid was applied to the cervix, and the features of the abnormal transformation zone were evaluated. The colposcopist used a 3-point scale to rate the degree of acetowhite change, the size of the lesion margin, and the blood vessel pattern in the lesion (Table 1). The site with the greatest point total for all 3 features was biopsied. A total of 301 patients had data available for evaluation. The women were an average of 40 years of age, and most (80%) were high school graduates, Forty-nine percent were in a committed relationship, 45% were smokers, and 43% were taking oral contraceptives. They had an average of 4 lifetime sexual partners and an average age at first intercourse of 17.3 years. Cervical cytology diagnosed atypical cells of undetermined significance (ASCUS) or a low-grade intraepithelial lesion (LSIL) in 81% of patients. Nineteen percent had a high-grade intraepithelial lesion (HSIL). Histologic examination of the biopsy specimen showed cervical intraepithelial neoplasia (CIN) 1 in 43 patients (14%) and CIN 2 or 3 in 96 (32%). Biopsy results were normal for 43% percent of patients (n = 162). In univariate logistic regression analysis, there was a significant association with the presence of CIN of any type for each of the 3 cervical features evaluated. A score of 2 points on the 3-point scale had an odds ratio for association with any CIN of 2.7 for lesion margin size, 10.1 for acetowhite change, and 2.0 for blood vessel pattern. However, when unconditional and stepwise multivariate regression analyzes were performed, the results of each analysis showed that only the degree of acetowhite change retained a significant association with CIN 2 or 3. A score of 2 had an odds ratio for association with CIN 2 or 3 of 2.4 for lesion margin size and 2.11 for blood vessel pattern compared with 22.1 for acetowhite change.

Prospective Evaluation of Colposcopic Features in Predicting Cervical Intraepithelial Neoplasia: Degree of Acetowhite Change Most Important

OBJECTIVE.: To prospectively evaluate the contribution of three colposcopic features-degree of acetowhite change, blood vessel pattern, and lesion margin-to the diagnosis of cervical intraepithelial neoplasia. MATERIALS AND METHODS.: A total of 301 women, who participated in two randomized controlled trials and a cross-sectional study of human papillomavirus testing and who were referred to a regional colposcopy center, were studied. Women were examined by colposcopists, who prospectively scored all abnormal transformation zones using three features. The site with the highest score (the most abnormal site) was biopsied and histology reviewed by two pathologists. RESULTS.: In multivariate analysis, degree of acetowhite change was the only feature significantly associated with cervical intraepithelial neoplasia. CONCLUSIONS.: Grading lesion severity using degree of acetowhite change alone gave comparable results to grading using the three combined features.

Freqüência de Neoplasia Intra-epitelial Cervical em Portadoras do Vírus da Imunodeficiência Humana

Objetivo: verificar a freqüência de neoplasia intra-epitelial cervical (NIC) em mulheres infectadas pelo vírus da imunodeficiência humana (HIV). Métodos: foram estudadas 99 mulheres HIV-soropositivas; o diagnóstico da infeccão pelo HIV foi realizado por meio de dois testes ELISA, complementados por teste Western blot ou de imunofluorescência indireta. Como grupo controle foram analisadas 104 mulheres que não apresentavam positividade no teste ELISA. Em ambos os grupos o rastreamento de NIC foi realizado por meio da associação de colpocitologia oncológica e colposcopia. Nos casos em que a colposcopia revelou existência de zonas de transformação anormal, o diagnóstico de NIC foi realizado mediante biopsia dirigida, complementada ou não por conização. Resultados: em 15 das 99 pacientes do grupo de estudo (15,2%) foi encontrada neoplasia intra-epitelial cervical, sendo dez casos de NIC I, um de NIC II e quatro de NIC III. Entre as 104 mulheres do grupo controle, quatro (3,8%) eram portadoras de neoplasia intra-epitelial cervical, encontrando-se um caso de NIC I e três de NIC III. Conclusão: a análise comparativa dos resultados evidenciou que a freqüência de neoplasia intra-epitelial cervical foi significantemente mais elevada entre as pacientes infectadas pelo HIV.

Combined Pap Smear, Cervicography and HPV DNA Testing in the Detection of Cervical Intraepithelial Neoplasia and Cancer

The sensitivity of the Pap smear (PAP) continues to be the subject of debate. During the past several years, cervicography (CER) and HPV DNA testing have been suggested as optional tools in the screening of cervical cancer precursors. The performance characteristics of PAP, CER and HPV DNA testing (hybrid capture test [HCT]) in all potential combinations were evaluated in a series of 1,030 women (aged 16-70, median, 33), subjected to colposcopy (COLPO) as the reference tool. Of the 992 evaluable cases, 402/992 (41%) had positive COLPO (i.e., an abnormal transformation zone). Of them, 298 women underwent directed punch biopsy, while of the COLPO negative patients, 18/93 positive by at least one of the three tests had endocervical curettage. Of the 402 COLPO positive women, 146 (36%) remained negative on all tests, whereas 256 (64%) had at least one positive test. There were 84 cervical intraepithelial neoplasia (CIN) 2 and 3 lesions and 6 invasive carcinomas. Of the former, 10 were detected by PAP alone, 4 by CER alone and 3 by HCT alone. Three of the 6 carcinomas were HCT negative. The predictive value (PPV) of a positive test was 45% for PAP, 51% for CER and 48% for HCT. The combinations of PAP with CER (for PAP negative cases) and PAP with HCT were more sensitive for CIN 2 and 3 (95% and 94%, respectively) as compared with PAP alone but were associated with a significant decrease in specificity (44% and 46% vs. 57%, respectively). However, both combinations retained a PPV (43%) similar to that of PAP alone (45%). The potential combinations of PAP with CER and with HCT were more sensitive in detecting CIN 2 and 3 as compared with PAP alone and retained a PPV similar to that of PAP.

A prospective study of biopsy-confirmed cervical intraepithelial neoplasia grade 1: colposcopic, cytological, and virological risk factors for progression.

The objective of this prospective study of histologically confirmed cervical intraepithelial neoplasia (CIN) (including equivocal CIN1) was to determine risk factors for progression to histologically confirmed CIN3, particularly human papillomavirus (HPV) types and cofactors. We postulated that HPV DNA positivity would be a strong, prospective risk factor for progression. Possible participants were referred with an abnormal cytological diagnosis of CIN1 or lower-grade disease or external genital warts. Women with histologically confirmed CIN1 (including koilocytotic atypia) or equivocal CIN1 were eligible for follow-up. Of these, 163 women were assessed every 3 months (if a lesion were present) or every 6 months (if a lesion regressed colposcopically during the course of the study), for up to 52 months. Progression was defined histologically, whereas persistence and regression were defined by combined cytological, colposcopic, and histological assessments. Subjects who progressed to a biopsy-confirmed CIN3 or who developed a lesion that was clinically unsafe to follow up (i.e., because of movement into the endocervical canal), were removed from the study and were treated. A total of 237 patients were evaluated as possible participants. The 74 exclusions at enrollment included 33 patients who had an entry diagnosis of CIN2 to CIN3 or who had lesions that were otherwise already unsafe to follow up, 39 who did not have a lesion on colposcopically directed biopsy, and 2 who were immediately noncompliant. Among the remaining 163 participants, the overall progression rate to histologically confirmed CIN3 was 8%, the persistence rate was 49%, and the regression rate was 43%. All progressions occurred among women who were HPV DNA-positive and had colposcopically immature abnormal transformation zones.

Operator variability in disease detection and grading by colposcopy in patients with mild dysplastic smears

To determine interoperator variability in the colposcopic evaluation of patients with mild dysplastic smears, retrospective comparison of colposcopy and biopsy results in 856 patients examined by 11 colposcopists in the Outpatient Colposcopy Clinic of "L. Mangiagalli" Institute, Milano, was performed. The patients underwent a complete colposcopic assessment and target biopsy on suspect areas if a screening smear showed mild dysplasia. Colposcopic findings and disease detection rate for each operator were compared. There was no significant (P > 0.05) difference in the recording of abnormal colposcopic findings. Significant differences were found, however, in abnormal transformation zone grading (P < 0.001), biopsy rate (P < 0.05), and squamocolumnar junction visualization (P < 0.005). There was no significant difference in overall disease detection (P > 0.5) but there was a statistically significant, inverse relation (r = -0.6, P < 0.01) between the high grade (cervical intraepithelial neoplasia grades 2 and 3) and low grade (human papillomavirus/cervical intraepithelial neoplasia grade 1) detection rate for each operator. High grade disease detection in patients with mild dysplastic smears is influenced the subjectivity of the colposcopic examination. This should be considered when planning optimal management for patients with mild dysplasia.

Significance of atypical cervical cytology in pregnancy.

To ascertain the significance of squamous atypia encountered during routine Papanicolaou smear screening in pregnancy, we reviewed our experience with 76 pregnant women seen during a 4-year period. All were evaluated with repeat cytology and colposcopy during pregnancy and again postpartum. Colposcopic examination during pregnancy revealed a normal transformation zone without evidence of intraepithelial neoplasia in 46 women. In six of these women, repeat cytology was interpreted as cervical intraepithelial neoplasia (CIN) grade 1. In 30 women, an abnormal transformation zone was identified--14 with a negative repeat cytology. In five women, the transformation zone was interpreted as compatible with CIN 2 or CIN 3. Colposcopically directed biopsies were performed in 31 women, in all but two postpartum. Of the 76 women, human papilloma virus or CIN was identified on biopsy in 16 women (21%). We propose that an isolated report of atypical squamous cells on cervical cytology obtained at the initial prenatal visit does not warrant colposcopic evaluation during pregnancy, unless a repeat cytology suggests CIN. Repeat cytology and evaluation to exclude infections and inflammatory lesions is appropriate. However, if a subsequent cytology is abnormal, postpartum colposcopy and colposcopically directed biopsies seem appropriate, since the prevalence of HPV or CIN was 21%.

Loop diathermy excision of the abnormal cervical transformation zone

Six-hundred patients with abnormal cervical transformation zones were treated by loop diathermy excision. The patients were referred to the colposcopy clinic in the Regional Department of Gynaecological Oncology, Gateshead with abnormal cervical cytology. The indications for treatment, management and follow-up are presented. All patients were managed as out-patients under local anesthesia (71%) or as half-day inpatients under short general anesthesia (29%). Patients were treated with loop diathermy excision of visible lesions or with loop diathermy conization as required. Eradication of cervical intra-epithelial neoplasia (CIN) was achieved with one treatment in 95.5% of cases of CIN. The procedure is rapidly and easily performed. Major morbidity is rare. Only two patients required blood transfusion following treatment. Loop diathermy excision is ideally suited to a policy of combined diagnosis and treatment for these patients allowing efficient use of clinic time. The danger of inadvertant local destruction of early invasive disease is minimized. When preliminary colposcopically directed punch-biopsy histology was compared to definitive loop histology, CIN3 was detected in 27.4% of loops where the punch biopsies failed to show CIN and one case of CIN3 on punch biopsy was upgraded to invasive squamous carcinoma on loop biopsy. Loop excision biopsy therefore gives more complete histologic information than traditional punch biopsy. This technique is effective, efficient, economical and highly acceptable to both patient and practitioner. It is now the treatment of choice for management of the abnormal transformation zone in our practice.

Preclinical cancer of the cervix: Diagnostic pitfalls

This paper outlines the pitfalls encountered in the diagnosis of 127 preclinical cancers of the cervix. Each patient had cervical cytology, colposcopy, and histology performed within the same institution. Early stromal invasion was diagnosed in 55 patients and occult invasion was diagnosed in 72 patients. For preclinical cancers as a group, the possibility of invasive carcinoma was predicted cytologically in 36% and suspected colposcopically in 41%. However, in over 85% of patients the abnormal transformation zone (TZ) extended into or was totally confined within the endocervical canal and could not be adequately evaluated with the colposcope. A feature of this study was the high incidence of incomplete excision of abnormal tissue by cone biopsy and a high incidence of residual disease at hysterectomy. Cone biopsy was necessary to accurately assess the maximum depth and extent of invasion prior to definitive therapy whenever invasion was suspected colposcopically or on target biopsy. In 10 of 16 such patients, the cone biopsy demonstrated occult invasion. Colposcopy and directed target biopsy alone was adequate for the diagnosis of frank invasive cancer in 22 of the 72 patients in the occult invasion group, enabling definitive therapy to be undertaken without further delay.

Colposcopic evaluation of DES-exposed progeny at two large medical centers: the squamous neoplasia problem.

Two hundred eight patients with confirmed or suspected diethylstilbestrol exposure were examined colposcopically at two separate medical centers. Cervicovaginal ridges were present in 90 (43.3%) and ectopy was found in 188 (90.4%) of the patients. Evidence of vaginal adenosis was present in 122 (58.6%) of the cases. Seventy-four percent of the patients had abnormal colposcopic findings: 15.4% having columnar epithelium on the surface of the vagina and 66% having abnormal transformation zones (white epithelium, punctation, mosaic). Twenty patients (9.6%) were initially identified histologically as having squamous dysplasia. Subsequent review of the histologic material in these cases could document only two cases of significant squamous dysplasia, both severe, the remainder having immature, atypical metaplasia or possibly very mild dysplasia. This finding emphasizes the problems encountered in histologically differentiating squamous neoplasia from the peculiar metaplasia found in these patients, thereby making it difficult to establish whether these patients are at increased risk for the development of squamous neoplasia.

Observations on the surface area of the abnormal transformation zone associated with intraepithelial and early invasive squamous cell lesions of the cervix

The apparent area of the abnormal transformation zone (TZ) of the cervix was measured in a total of 104 patients by a simple method with the use of the 1 and 5 mm. diameter circle in the center of the field of the Leisegang colposcope and the field of the colposcope itself. The visible area (mean ± S.E.M.) of the abnormal TZ for five patients with microinvasive or occult carcinoma of the cervix (180.8 mm.2 ± 62.2) was significantly larger (p < 0.01) than that of 64 patients with major intraepithelial lesions (62.5 sq. mm.2 ± 7.3) and 35 patients with minor intraepithelial lesions (45.8 sq. mm.2 ± 11.7). The visible area of the abnormal TZ measured over 40 mm2 in each of the five patients with invasive lesions but in only 42 of 99 (42 per cent) patients with intraepithelial lesions. The TZ extended into the endocervical canal and could not be fully visualized in four (80 per cent) of the patients with invasive lesions, 24 (38 per cent) of patients with major intraepithelial lesions, and 11 (31 per cent) of patients with minor intraepithelial lesions. The implications of these findings are discussed.

Colposcopy-neglected method of cervical evaluation.

The colposcope is essentially a binocular microscope of low power. It is especially valuable for inspecting the epithelium of the portio vaginalis cervicis. There are four findings classified as simple atypical changes: simple leukoplakia, ground leukoplakia, mosaic leukoplakia, and non-iodine-staining areas. In addition, the observer looks for true erosion, abnormal blood vessels with proliferation, and abnormal transformation zones. The colposcopic findings in 49 cases of cervical carcinoma are summarized and clearly show the value of such data. While cytological methods have the great advantage of being able to detect many endocervical lesions, the methods of colposcopy often determine the location of the epithelial abnormality.