A real time optoelectronic device as an adjunct to the Pap smear for cervical screening: a multicenter evaluation.

We report on the results from a multicenter trial for a real time optoelectronic device as an adjunct to the Pap smear for cervical screening. TruScreen (Polartechnics Limited, Sydney, Australia) is an automated device which measures the response to optical and electrical stimulation of the cervix and returns a screening result in real time. Analysis was performed on a group of 651 subjects recruited at 10 centers. Cytology and histology analyses were performed by centralized laboratories, with the cytology classification performed according to the Bethesda 2001 system. The sensitivities for histologically confirmed CIN 2/3 lesions by TruScreen, Pap, and TruScreen/Pap combined were 70% (95% CI: 67-74), 69% (CI: 65-72), and 93% (CI: 91-95), respectively. For histologically reported CIN 1, the sensitivities of the TruScreen, Pap, and combined test were 67% (CI: 63-70), 45% (CI: 41-49), and 87% (CI: 84-89). The improvement in sensitivity for the combined test compared to the Pap smear alone was significant (P = 0.002). Because TruScreen and cytology detect partly different but overlapping groups of CIN cases, the adjunctive combination provides very high CIN detection rates.

Early invasive (FIGO stage IA) carcinoma of the cervix: a clinico-pathologic study of 476 cases.

The clinical and histologic features of 476 tumors fitting the 1995 FIGO definition of stage IA cervical cancer, treated at a Sydney tertiary referral hospital between 1953 and 1992, are reviewed. Five-year follow-up was complete with a median of 10 years. The diagnosis was increasingly made by histologic examination of colposcopically directed cone biopsy. The majority (88%) of tumors were squamous. The proportion of both younger women (3 mm. Treatment was surgical in 99% and was increasingly more conservative as the study progressed with no apparent increase in treatment failure. From 1973 treatment by cone biopsy rose from 6.5 to 35%, by radical hysterectomy fell from 51 to 21% and by lymphadenectomy from 53 to 26%. Only one of 115 patients treated by cone biopsy died. Positive lymph nodes were detected in 1.7% of 180 patients undergoing lymphadenectomy. There were 16 recurrences (3.4%); six vaginal with no cancer deaths, nine pelvic and one distant, with nine deaths and three new cancers (two deaths). Univariate analysis suggests that older age, glandular tumors and those invading 3 mm were associated with more treatment failures and multivariate analysis showed that both conservative hysterectomy and the omission of lymphadenectomy are associated with higher recurrence rates with >3 mm invasion. The study failed to resolve the dilemma of predicting those tumors with a poor prognosis.

The Polarprobe--emerging technology for cervical cancer screening.

The Polarprobe is a portable non invasive electronic device designed for the detection of cervical precancer and cancer. It measures both electrical and optical properties of cervical tissue to allow a real time comparison with a databank of previously determined cervical tissue types. The need for additional tests to augment or even replace the Papanicolaou smear has partly prompted its development. Indeed it has been shown to be associated with less pain and anxiety than the smear and has the capability of encouraging women to attend for screening. Some of the preliminary clinical trials on the Polarprobe are reported as well as the ongoing developments and modifications to the device.

An electronic approach to the detection of pre-cancer and cancer of the uterine cervix: a preliminary evaluation of Polarprobe.

We report on the testing of a prototype of an electronic device for the detection of cervix cancer and its precursors, known as the Polarprobe. The device monitors three aspects of the cervix tissue; two relate to optical properties and the other to dielectric characteristics. The response to tissue stimulation takes the form of an energy pattern which, in conjunction with spectroscopic discriminants, can be digitized to prepare an algorithm. The pattern algorithms are sufficiently characteristic to be afforded names which correspond to tissue states recognizable as normal or abnormal by the clinician. On a tissue observation basis the previously established recognition algorithms derived from 106 volunteers produced assessments which related strongly to colposcopy/histology diagnoses obtained on 77 additional volunteers. This concordance between colposcopy/histology and Polarprobe diagnoses on this primary analysis subgroup ranged from 85% on low-grade intraepithelial abnormalities, and 90% on high-grade cervical intraepithelial squamous neoplasia, to 99% on invasive cancer. An extrapolation of these results suggests false-positive/false-negative rates in the order of 10% are achievable with the current Polarprobe device.

The efficacy of postoperative vaginal irradiation in preventing vaginal recurrence in endometrial cancer.

Between 1960 and 1985 hysterectomy was performed on 811 FIGO stage I and 116 stage II endometrial cancers which were divided into three groups: low-risk stage Ii (grade 1 and 2 lesions confined to the inner third of the myometrium; high-risk stage Iii (grade 3 and/or invading to the middle third of the myometrium or beyond); and FIGO stage II tumors (also high-risk). Hysterectomy was the only treatment in 492; in 145 the vaginal vault alone was radiated and in 290 the whole vagina, in each instance by an intracavity dose of 60Gy; in 34 of the latter high-risk tumors the pelvis received an additional 46Gy by external beam therapy. Forty isolated vaginal recurrences were detected; 10 in 308 low-risk and 22 in 184 high-risk tumors treated by surgery alone, and two and five in 40 low and 105 high-risk patients, respectively, who received adjuvant vault irradiation. No recurrences followed irradiation of the whole vaginal mucosa in 163 stage Ii low-risk and 40 stage II lesions and one, 9 years later, in 87 high-risk stage Iii tumors. Nearly 45% of patients with vaginal recurrence died from cancer within 1 year, 77% within 5 years and only 10% survived their recurrence 10 years. Total vaginal irradiation eliminated vaginal recurrences in low risk and reduced the incidence to 2.1% at 20 years after high-risk tumors.

Colposcopic differentiation of abnormalities arising in the transformation zone.

When metaplastic cervical epithelium is exposed to the factors responsible for neoplasia, the transformation zone becomes atypical. These changes, visible as acetowhite epithelium, altered vascular patterns, and irregular surface contour, are easily recognized through the colposcope in most patients. It is possible to grade the changes to determine the severity of the abnormality and so, in consultation with the patient, decide on the best management course. However, there will always be lesions where colposcopy is indeterminate, and biopsy of such lesions is mandatory. Combined colposcopy and histology are still the mainstays of clinical management. As yet, more refined investigations, such as HPV-subtype determination, have not demonstrated any advantage for these patients.

A randomized trial comparing platinum-based chemotherapy followed by radiotherapy vs. radiotherapy alone in patients with locally advanced cervical cancer.

Seventy-one patients with stage IIb-IVa cervical cancer were entered on a randomized trial comparing standard pelvic radiotherapy vs. 3 cycles of combination chemotherapy with cisplatin, vinblastine and bleomycin followed by pelvic radiotherapy. Four out of 34 patients randomized to PVB followed by radiotherapy received no PVB and a further 3 patients had only one or 2 cycles of chemotherapy prior to radiotherapy due to drug-related toxicity or progressive disease. After a median follow-up of 3.1 years, no significant difference in survival has emerged between the two randomized groups. However, a difference in the pattern of relapse is emerging with a relatively reduced frequency of systemic relapse in patients receiving chemotherapy prior to local radiotherapy compared to radiotherapy alone. Tumor response was seen following PVB treatment and prior to radiotherapy in 47% of patients. Overall the tumor response rate following completion of radiotherapy was 89% in those treated by radiotherapy and 94% after PVB+radiotherapy. Thirty-three percent of patients randomized to radiotherapy alone relapsed first at a distant (extra pelvic site), and only 18% of patients randomized to initial PVB followed by radiotherapy relapsed systemically initially. When results are presented according to treatment actually given, these trends in patterns of treatment failure are magnified. No treatment-related deaths were reported, and there was no excess of complications with pelvic radiotherapy in the group who had received prior PVB chemotherapy.

A randomized trial of adjuvant chemotherapy after radical hysterectomy in stage Ib-IIa cervical cancer patients with pelvic lymph node metastases.

Seventy-one patients with Stage Ib-IIa cervical cancer treated by radical hysterectomy and found to have pelvic lymph node metastases were entered on a randomized trial comparing standard pelvic radiotherapy versus three cycles of combination chemotherapy with cisplatin, vinblastine, and bleomycin followed by pelvic radiotherapy. After a median follow-up of 2.5 years, 24 patients have relapsed. In 12 patients, the first evidence of relapse was in the pelvis, in 11 patients the first relapse was evident at a distant site, and in 1 patient the local recurrence and distant metastases were documented simultaneously. No difference in disease-free or overall survival has emerged between the two treatment groups. Relapse was more common in patients with non-squamous tumors (44%) and in those with metastases in several pelvic lymph nodes. We conclude that patients with pelvic lymph node metastases have a rather poor prognosis, but it remains to be determined how they should best be treated after radical surgery.

Colposcopic features of papillomaviral infection and premalignancy in the female lower genital tract.

Colposcopy plays an important role in the investigation and direct management of papillomavirus infection of the female lower genital tract. The colposcopic appearance of subclinical papillomavirus disorders resembles intraepithelial neoplasia, and the matter is further confused in that subclinical lesions are often accompanied by intraepithelial neoplasia into which they grade with indefinite borderlines. High accuracy in prediction of histologic diagnosis in the spectrum that ranges from subclinical papillomavirus infection to major grades of intraepithelial neoplasia may be achieved by a system of grading of colposcopic appearances.

Percutaneous urinary diversion in gynecologic oncology.

During the 10-year period after 1979, percutaneous urinary diversion (PCUD) was performed on 35 patients whose mean age was 53.5 years (30-80 years). Twenty-one patients (60%) had Stage IIB-IV cervical cancer, 11 (31%) Stage IB-IIA cervical cancer, 2 (6%) Stage IB-II endometrial cancer, and 1 (3%) Stage IB vaginal cancer. All had radiological evidence of ureteric obstruction and 8 patients also had urinary tract fistulae. Serum creatinine levels were elevated in 24. Following diversion there was a significant fall in mean pretreatment creatinine levels from 482 mumol/liter (range, 70-1703 mumol/liter) to 131 mumol/liter (range, 60-290 mumol/liter; P less than 0.0001); those patients with normal creatinine levels prior to diversion also had a reduction in their levels. A significant fall in mean serum urea levels from 22.0 mmol/liter pre- to 11.9 mmol/liter post-PCUD (P less than 0.001) was also noted. Minor complications occurred and included hemorrhage, replacement/reinsertion, infection, and blockage. Median survival of the 35 patients after PCUD was 6 months (mean, 16.5 months). For the 11 with normal pretreatment renal function median survival was 16 months (mean, 41 months) compared to 2.5 months (mean, 5.1 months) for those with elevated pretreatment serum creatinine levels. Median survival with untreated malignancy was 7 months (mean, 19.6 months) and 6 months (mean, 12.3 months) in patients with previously treated cancer. PCUD is indicated in previously untreated patients with gynecologic cancer so that primary therapy can be instituted. The role of urinary diversion in patients with previously treated cancer must be individualized. Palliative diversion is appropriate in selected patients where additional therapy is expected to prolong life, where symptom control is needed, or to allow the patient to return home for a significant proportion of the remainder of life.

A comparative study of proliferating (borderline) and invasive epithelial ovarian tumours in young women.

A series of 18 patients with proliferating or borderline ovarian tumours and 18 with invasive ovarian tumours is discussed. Proliferating tumours occurred at a younger mean age than invasive disease, and presented at an earlier stage, both contributing factors to their more favourable outlook. Histopathological assessment revealed that the majority of both proliferating and invasive tumours were of serous origin. Mucinous cell type occurred less often as did the endometrioid and clear cell types. The management of the proliferating tumours involved 'radical' surgical procedures in 11 of 18 (61.6%) patients. Only 7 patients (38.8%) had conservative surgical procedures performed. Six patients (33%) had adjuvant chemotherapy while 2 (11%) also underwent abdominopelvic irradiation. All patients with invasive disease had radical surgery and adjuvant chemotherapy and 2 also received abdominopelvic irradiation. The fact that epithelial malignancies of the ovary do occur in younger women needs to be remembered by gynaecologists contemplating surgical procedures on younger patients with adnexal masses. Proliferating or borderline tumours tend to occur more frequently in the younger age groups, and contrary to the implication of their name, they are associated with significant morbidity and mortality.

Changing character of cervical cancer in young women.

To examine the hypothesis that the pattern of cervical cancer is changing data on women presenting with the disease over 34 years were studied retrospectively. During 1953-86, 2628 women with cervical cancer were referred to a large tertiary referral hospital in Sydney; 418 were aged 35 or less. During the period of review the proportion of young women with the disease increased from under 9% in the 1950s and 1960s to about 25% in the 1970s and 1980s; a similar but less pronounced trend was apparent for the whole of New South Wales in the 1970s and 1980s. The prevalence of less common morphological types of cervical cancer increased throughout the period, particularly in the young. Pelvic lymph node metastases were identified in younger patients with stage Ib and IIa tumours more commonly in the later years of the study, suggesting that the disease was becoming more severe. Overall rates of recurrence improved over time, but an apparent increase in early recurrences was observed in young patients with Ib and IIa tumours and without nodal disease. The results suggest that the clinical and pathological behaviour of cervical cancer changed over the period of review.

Papillomavirus and cervical cancer: a clinical and laboratory study.

It is now widely accepted that HPV types 16, 18, 31, and 33 are associated with the development of high grade intraepithelial neoplasia and malignant lesions in the cervix. On this basis, the identification of HPV types in cervical scrape samples has been advocated as a supplement to cytological screening tests. However, little is known of the distribution of the virus at different sites in the lower female genital tract or of how this distribution may change during the natural course of HPV infection. In this survey, HPV DNA dot hybridizations and, in some instances, Southern blot hybridizations with mixed HPV 6/11 and 16/18 probes were undertaken to detect HPV DNA in cervical scrapes and biopsies of the cervix, vagina, and vulva. A total of 92 women attending a Sydney hospital were screened: 59 of these patients had cervical disease, either invasive cervical carcinoma (CaCx) or cervical intraepithelial neoplasia (CIN), grades I-III. A group of 33 women who lacked evidence of cervical abnormalities served as controls. HPV DNA, predominantly type 16/18, was detected in the cervical biopsies of 96% of the CaCx patients, 80% of the CIN III patients, and 65% of the CIN I-II patients. In contrast only 9% of the cervical biopsies from the control group contained detectable HPV 6, 11, 16, or 18 DNA. A high proportion of the women with cervical abnormalities had evidence of concurrent vaginal and/or vulval papillomavirus involvement. The significance of these findings for routine screening and subsequent management of patients with HPV-associated cervical disease is discussed.

Effects of sperm protamine on human cervical epithelial cells and BHK 21 cells in vitro.

The addition of protamine, of both human and animal origin, to cultures of epithelial and fibroblastic cells has demonstrated that this component of sperm proteins may be capable of bringing about neoplastic transformation in vitro.