John L. Benedet

A comprehensive program for cervical cancer detection and management

OBJECTIVE The purpose of this study was to document some of the results of a comprehensive provincial cytology and colposcopy program for the year 1988 and also to review the impact on the incidence and mortality rates for a clinical carcinoma of the cervix. STUDY DESIGN This study is a retrospective analysis of the cytologic results of all patients examined provincially in 1988 and a review of the clinical records of patients diagnosed with invasive cancer and those who died of disease. RESULTS In 1988 490,985 women (40% of all women over the age of 15 in the population) were screened, with 9.2% showing abnormal cells. A total of 79% of women screened were less than 50 years old and accounted for 86.3% of all abnormal smears. Women less than 35 years old were more likely than older women to have moderate dyskaryosis or worse. CONCLUSION Intensive comprehensive cytology and colposcopy programs reduce not only the incidence and mortality of clinical carcinoma of the cervix but also rates of in situ disease and other precursors.

Stage ia carcinoma of the cervix revisited

Objective To examine some of the controversy that still exists regarding the definition and management of microinvasive or early invasive cervical carcinoma, in particular, the current concepts regarding the definition of these conditions and their inclusion into the staging system for cervical cancer. Data Sources A MEDLINE search was used to identify English-language reports of clinical and pathologic information on cervical cancer. Articles published during 1970–1993 were reviewed. Methods of Study Selection Articles were selected for review if the information published contained data regarding measured depth of invasion, histologic examination of lymph nodes, and lymphatic vascular space status with these tumors. Tabulation, Integration, and Results: Results from the studies were pooled to determine the correlation between depth of invasion with the likelihood of nodal disease and recurrence, both with and without lymphatic vascular space involvement. These studies indicated that the likelihood of recurrence and death from cancer, together with the presence of nodal metastasis, appears to be directly related to the depth of tumor invasion. The relative importance of factors such as lymphatic space involvement will likely remain controversial because they may not be independent prognostic factors. Conclusion Review of the literature suggests that although no uniform opinion exists as to how these conditions should be described or managed, the evidence indicates that some modifications to the 1985 staging system for cervical cancer could be made to better categorize patients with these conditions and also, perhaps, provide guidelines for management.

Colposcopic evaluation of abnormal Papanicolaou smears in pregnancy

Colposcopy was used to examine 401 pregnant patients with cytologic or clinical abnormalities of the cervix to determine if routine biopsy could be safely omitted except where the colposcopic impression was one of possible invasive carcinoma. A comparison of the antepartum colposcopic impressions with the postpartum histologic diagnosis revealed agreement to within one degree in 87% of patients, with 3% of patients showing a more advanced lesion than that anticipated. Only 2% of patients showed a progression of cytologic abnormalities at postpartum examination; 39% showed marked improvement. Four of nine patients with invasive carcinoma were diagnosed at antepartum colposcopy, with an additional two patients recognized as having invasive cancer at the postpartum colposcopic examination. The omission of routine biopsy is less than ideal if only one antepartum colposcopy is performed, since a considerable period of time may elapse before the patient is seen again postpartum. Those situations in which it may be omitted, together with guidelines for the management of pregnant patients with abnormal cervical cytologic findings, are presented.

Basal cell carcinoma of the vulva: Clinical features and treatment results in 28 patients

Objective To review our experience and that in the recent literature regarding basal cell carcinoma of the vulva to see whether current management guidelines are appropriate. Methods Twenty-eight women with basal cell carcinoma of the vulva were seen over 25 years at the BC Cancer Agency. The clinical-pathologic features were tabulated and the outcome was analyzed. Results The mean age was 74 years, and almost two-thirds were over the age of 70 at diagnosis. Patients typically presented with an irritation or soreness, with a symptom duration ranging from a few months to several years. Most lesions were confined to the anterior half of the vulva, and 23 of the 28 patients had T1 lesions. Wide local excision was the treatment method used most commonly. Only one patient was known to have died from disease metastasis. Ten women had other basal cell carcinomas, either before or after the diagnosis of their vulvar lesions, and in ten patients 11 other malignancies were diagnosed. Conclusion Basal cell carcinoma of the vulva is an extremely uncommon tumor that rarely metastasizes or spreads. Primary treatment should consist of wide local excision and continued follow-up.

See-and-treat strategy for diagnosis and management of cervical squamous intraepithelial lesions

In a see-and-treat protocol, patients referred for colposcopy because of an abnormal Pap smear in cervical-cancer screening can be treated by loop excision, without biopsy, during one visit to the clinic. However, overtreatment in the see-and-treat strategy has been reported to be 1.2-83.3% for low-grade squamous intraepithelial lesions (SIL) and to be 13.3-83.3% for high-grade SIL. Range of overtreatment narrowed to 4.0-23.5% for those with normal pathology and to 18.0-29.4% for those with normal or low-grade pathology when calculation of overtreatment was restricted to patients diagnosed with high-grade SIL on colposcopy and referral Pap smear. Most common treatment complications are bleeding and infection. Nonetheless, the strategy has become accepted internationally: low costs, decreased patient anxiety, and increased compliance make it appealing, especially in settings with limited health resources, and for patients at risk of not being treated in a timely manner or of not returning for a second appointment. Mathematical modelling may give information about the appropriateness and usefulness of this treatment while the results of long-term clinical trials are awaited.

DNA ploidy compared with human papilloma virus testing (Hybrid Capture II) and conventional cervical cytology as a primary screening test for cervical high-grade lesions and cancer in 1555 patients with biopsy confirmation

Because 80% of cervical cancers arise in low‐resource settings, many inexpensive strategies are being tested. In that spirit, the authors are testing large‐scale genomic or DNA ploidy measurements as an inexpensive and semiautomated strategy.

Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia: Testing a device as an adjunct to colposcopy

Testing emerging technologies involves the evaluation of biologic plausibility, technical efficacy, clinical effectiveness, patient satisfaction, and cost‐effectiveness. The objective of this study was to select an effective classification algorithm for optical spectroscopy as an adjunct to colposcopy and obtain preliminary estimates of its accuracy for the detection of CIN 2 or worse. We recruited 1,000 patients from screening and prevention clinics and 850 patients from colposcopy clinics at two comprehensive cancer centers and a community hospital. Optical spectroscopy was performed, and 4,864 biopsies were obtained from the sites measured, including abnormal and normal colposcopic areas. The gold standard was the histologic report of biopsies, read 2 to 3 times by histopathologists blinded to the cytologic, histopathologic, and spectroscopic results. We calculated sensitivities, specificities, receiver operating characteristic (ROC) curves, and areas under the ROC curves. We identified a cutpoint for an algorithm based on optical spectroscopy that yielded an estimated sensitivity of 1.00 [95% confidence interval (CI) = 0.92–1.00] and an estimated specificity of 0.71 [95% CI = 0.62–0.79] in a combined screening and diagnostic population. The positive and negative predictive values were 0.58 and 1.00, respectively. The area under the ROC curve was 0.85 (95% CI = 0.81–0.89). The per‐patient and per‐site performance were similar in the diagnostic and poorer in the screening settings. Like colposcopy, the device performs best in a diagnostic population. Alternative statistical approaches demonstrate that the analysis is robust and that spectroscopy works as well as or slightly better than colposcopy for the detection of CIN 2 to cancer.

The quality of community Colposcopic practice

OBJECTIVE: To estimate the quality of community colposcopic practice in British Columbia through an assessment of the degree of correlation between colposcopy, cytology, and histology. METHOD: We reviewed all new-patient colposcopies in British Columbia during 2001 by 37 gynecologists in 24 hospital-based clinics. RESULTS: Colposcopic impression closely mirrored the referral cytology diagnosis in 89.8% of cases. As with cytology-biopsy comparisons, discordant cases were more likely to be overestimates of disease rather than underestimates, 18.8% versus 1.8%. Overestimates were usually biopsy sampling errors rather than false positive cytology. The overall correlation between cytology and biopsy was considered satisfactory in 79.4% of cases. Satisfactory agreement between the colposcopic diagnosis and accompanying biopsies occurred in 86.8% of patients. Five colposcopists had performance scores below this standard. Colposcopy with a sensitivity of 90.3% and a specificity of 57.3% as practiced in this provincial program would appear to be of a satisfactory level. The rate of intraepithelial or invasive disease increased from 40.6% in patients with low-grade squamous intraepithelial changes to 91.9% in patients with suspicious or malignant cytology. The value of the colposcopic impression to identify disease correlated best with the higher the grade of disease predicted (64.6% to 92.6%). CONCLUSION: A measure of the colposcopic proficiency in the community can be estimated by comparing the level of agreement between the presenting cytology, colposcopic impression, and corresponding directed biopsies. The results of this study would indicate that 5 individuals had practice standards that were below average. An integrated cytology-colposcopy program facilitates the assessment and identification of below-average practice standards in a community. LEVEL OF EVIDENCE: III

Adenocarcinoma in situ of the vagina. A case report

The clinical and pathological features of a case of adenocarcinoma in situ of the vagina diagnosed in a 40‐year‐old woman with a negative history for intrauterine DES exposure are reported. The lesion was diagnosed 15 months following hysterectomy for in situ squamous cell and in situ adenocarcinoma of the cervix. The vaginal lesion closely resembled colposcopically, cytologically, and histologically previously described cases of cervical adenocarcinoma in situ. The case was of additional interest pathologically because of a focal signet‐ring cell component which exhibited extensive pagetoid invasion of the adjacent squamous mucosa. No previously reported examples of vaginal adenocarcinoma in situ could be found. The histogenesis of this entity is briefly discussed.

Costs of colposcopy services and their impact on the incidence and mortality rate of cervical cancer in Canada.

Objective Organized cervical cancer screening services consisting of conventional Papanicolaou cervical smears, colposcopy, and related treatment modalities are readily available in all provinces. The purpose of this report was to study the impact of colposcopy usage and costs on cervical cancer incidence and mortality rates in several Canadian provinces. Knowledge of such information is essential before newer technology such as liquid-based cytology and human papillomavirus testing is introduced or replaces the traditional systems used. Materials and Methods The Ministries of Health of five provinces were contacted and asked to furnish information on the number of colposcopic services and fee-for-service costs for these and for cryosurgery, carbon dioxide laser vaporization, loop electrosurgical excisions, and cold-knife conizations for the year 2000. Canadian Cancer Society estimates of incidence and mortality rates for cervical cancer were also obtained. Results All provinces had similar incidence and mortality rates for cervical cancer; however, the number of colposcopic services on a per-capita basis varied substantially, with Manitoba and Ontario having rates that were approximately two or three times higher. Fee-for-service payments for colposcopy were similar in the Provinces studied but unit costs for surgical treatment services were highest in Ontario and British Columbia. Conclusions Although both the incidence and mortality rates for cervical cancer in Canada fell dramatically after the Walton Report in 1976, these rates have plateaued over the past decade despite widespread availability of colposcopy and related ambulatory treatment services. Higher rates of colposcopy usage do not seem to result in lower incidence rates for this disease. Unit costs for colposcopy are similar among the provinces reviewed, but substantial difference exists for certain treatment services. Additional studies are recommended before the widespread introduction or replacement of existing methods with newer, more costly techniques.