Effects of screening on cervical cancer incidence and mortality in New South Wales implied by influences of period of diagnosis and birth cohort.

STUDY OBJECTIVES: Cervical cancer incidence and mortality in NSW during 1972-1996 is examined under counterfactual assumptions to estimate the number of new cervical cancer cases averted and deaths avoided, with projections to 2006. SETTING: Cervical cancer incident cases and deaths in NSW for 1972-96 were obtained from the NSW Central Cancer Registry, Sydney, Australia. DESIGN: Data were analysed by age-period-cohort (APC) modelling, using Poisson regression. Projection of incidence to 2006 was based on a linear trend for period effects. A counterfactual scenario was constructed assuming stable period effects (1972-74), but modelled cohort effects. Modelled rates were converted to cases and deaths (using mortality:incidence ratios for cervical cancer), and compared with actual data to estimate cancers prevented and deaths averted due to screening. RESULTS: Rising cohort effects with recency of birth were found after controlling for age and period of diagnosis, and declining period effects were identified after controlling for age and birth cohort. The estimated cumulated number of new cases of cervical cancer prevented during 1972-1996 was 3440. The cumulated number of averted deaths over 1972-1996, derived from incident cases, was estimated to be 1610 (including actual declines in the M/I ratio). With no change in the M/I ratio from 1972, estimated cumulated mortality averted due to cervical cancer for 1972-1996 was 1210 deaths. CONCLUSIONS: Cervical screening has prevented a substantial number of new cases of cervical cancer and deaths. In addition, secondary prevention and improved treatment has contributed further to cervical cancer deaths averted.

Cervical screening by socio-economic status in Australia.

OBJECTIVES: To examine differentials and time trends in self-reported Pap test rates by socio-economic status (SES) from the 1989/90 and 1995 Australian National Health Surveys (NHS). METHODS: The unit record data for females were extracted from the two NHSs and combined. The outcome variable of interest was 'having a Pap test in the past three years'. The principal study factor was SES measured as individual characteristics and SES of area of residence. Migrant status, rurality, year of survey and age were controlled for in logistic regression models. RESULTS: Self-reported rates of having a Pap test in the past three years were higher in women from higher compared with lower SES groups. Compared with women with a bachelor or higher degree, the odds of reporting having a Pap test in the past three years in women with no post-school qualification was 0.86 (p<0.0005). Women with a gross annual income of less than $20,000 had significantly lower odds (OR=0.79) compared with women earning $40,000 or more. Blue collar (OR=0.84) and not employed (OR=0.73) women also had significantly lower odds compared to the referent white collar group. CONCLUSION: This study reveals differentials in Pap screening behaviour by individual measures of SES in Australia. Area-based SES measures under-estimated the SES differentials in Pap test rates compared with individual measures. Derived population attributable fractions reveal that about a quarter of self-reported under-screening is accounted for by low SES when measured individually, compared to 8% when SES is measured ecologically.

Relative expression of progesterone receptors A and B in endometrioid cancers of the endometrium.

The nuclear receptor for the female hormone progesterone (PR) is widely expressed in uterine cancer. PR is expressed as two proteins (PRA and PRB) with different functions, and in vitro evidence reveals PRA to inhibit PRB function, so the cellular ratio of PRA:PRB is likely to be an important determinant of progesterone action. The relative expression of PRA and B and their involvement in the pathogenesis of endometrial cancer is not known. The aims of this study were to determine PRA and B expression by dual immunofluorescent histochemistry in endometrial adenocarcinomas compared with expression in normal and hyperplastic glands, and to correlate expression in tumors with clinical features including grade. Significantly lower PR levels were found in tumors compared with normal glands and areas of complex atypical hyperplasia within the same specimen. The normal glands expressed both of the isoforms at similar levels, whereas there was increased predominance of one isoform in hyperplastic areas and in tumors, which suggested that the loss of coordinated expression of PR isoforms was an early event in tumor progression. The majority of tumors [27 (58%) of 46] expressed only one PR isoform, and the proportion expressing either PRA or B was the same [14 (30%) of 46, and 13 (28%) of 46, respectively]. One-half of all tumors ([23 (50%) of 46] expressed either PRA only or a predominance of PRA, and a few tumors [10 (22%) of 46] expressed comparable levels of PRA and B. Similar levels of PRA and B were noted only in FIGO grade 1 tumors, whereas higher grades (2 and 3) were associated with a predominance of one isoform. In summary, expression of only one PR isoform was common in endometrial cancers, which indicates that the decreased PR levels observed in these cancers arise from the loss of one PR isoform. Expression of a single PR isoform was associated with higher clinical grade, which suggests a relationship between the loss of PR isoform expression and features of poorer prognosis. Disruption of relative PR isoform expression was observed in complex atypical hyperplasia, which suggests that early alterations in the ratio of PRA:PRB may precede and/or be implicated in the development of endometrial adenocarcinoma. Alterations in the ratio of PR isoform expression are likely to cause disordered regulation of target genes, resulting in altered progestin action in the uterus, and this may be involved in the pathogenesis of endometrial cancer.

Cervical screening in migrants to Australia.

OBJECTIVE: To examine differentials and time trends in self-reported Pap test rates by migrant status from the 1989/90 and 1995 Australian National Health Surveys (NHS). METHOD: Unit record data for females with the variables of interest were extracted from the 1989/90 and 1995 NHS and combined. The dichotomous outcome variables were 'ever had a Pap test' and 'had a Pap test within three years'. The principal study factor was country-of-birth, but language spoken at home (English or not) was also examined. The indirect age-standardised screening ratio was used to calculate proportions of 'ever had a Pap test' and 'had a Pap test within three years' and differences were tested statistically using logistic regression analysis for each year of survey by migrant status. RESULTS: Odds ratios for rates of reporting 'ever had a Pap test' were significantly lower in women born in southern Europe, Italy, other countries, southern Asia, Middle East, Greece and South-East Asia compared with Australian-born. Reported rates of 'ever had a Pap test' were significantly higher in the 1995 NHS (p<0.001). There were significant increases in screening for the Australian-born, New Zealand-born, and women born in southern Europe, South-East Asia, South Asia and Italy, and both English and non-English speakers over the 1989/90 and 1995 NHSs. Odds ratios for reporting 'had a Pap test within three years' showed significantly lower ORs for women born in the UK, Other countries, Middle East, Greece, and South-East Asia compared with the Australian-born. CONCLUSIONS: This study reveals differentials in reported Pap test behaviour by country-of-birth in Australia and that reported screening rates have improved from the 1989/90 NHS to 1995 NHS in most country-of-birth groups.

Multimodality therapy for patients with clinical Stage I and II malignant mixed Müllerian tumors of the uterus.

BACKGROUND: The role of adjuvant therapy in the management of patients with malignant mixed Müllerian tumors (MMMT) of the uterus has not been defined. The outcome of planned multimodality therapy for patients with apparent early stage disease was assessed. METHODS: A pilot study was performed on 38 patients with clinical Stage I or II MMMTs of the uterus who were offered treatment according to a standard protocol. The protocol consisted of removal of the uterus, fallopian tubes, and ovaries and surgical staging followed by tailored radiation therapy and chemotherapy, consisting of cisplatin and epirubicin. RESULTS: The overall survival was 74% (28 of 38 patients), with a mean duration of follow-up for survivors of 55 months (range, 17-121 months). The mean time to death from disease was 26 months (range, 7-87 months). The survival rate for those patients who completed treatment according to the multimodality protocol was 95% (20 of 21 patients), with a disease free survival rate of 90% (19 of 21 patients). The overall survival of patients who did not receive the recommended treatment protocol for various reasons was 47% (8 of 17 patients). An analysis of survival curves demonstrated that there was a significant survival advantage for those patients who completed the treatment according to the multimodality protocol (P = 0.01). CONCLUSIONS: In this pilot study, patients with clinical Stage I or II MMMTs who underwent surgical staging and aggressive adjuvant radiation and chemotherapy had an excellent survival rate. The results justify a randomized prospective study of this approach.

The role of the clinical psychologist in gynecological cancer.

Gynecological cancers, which account for a substantial proportion of cancer cases in women, can precipitate a wide range of psychological difficulties including affective disturbances, sexual problems, certain somatic symptoms, and family issues. The clinical psychologist has a unique contribution to make in the assessment and treatment of the psychological needs of gynecological cancer patients, while also conducting research and providing training for health professionals regarding the psychological issues associated with gynecological cancer. Although the gynecological cancer setting affords the clinical psychologist multiple personal benefits, strategies must usually be implemented to minimize any negative impact arising from working in an area of considerable psychological stress.

Integrated multimodality therapy for embryonal rhabdomyosarcoma of the lower genital tract in postpubertal females.

Embryonal rhabdomyosarcoma of the female lower genital tract is generally regarded as a neoplasm occurring in childhood, but has also been reported in adults. The philosophy of therapy, largely based on data obtained from pediatric patients, has evolved slowly from ultraradical surgery, without adjuvant therapy, to neoadjuvant chemotherapy followed by less radical surgery and postoperative radiation. We report here three cases of lower genital tract rhabdomyosarcoma in postpubertal females. A failure to observe complete responses from any single treatment modality suggests that for embryonal rhabdomyosarcoma in adult and adolescent women a multimodality approach to therapy is essential.

Resection of bulky positive lymph nodes in patients with cervical carcinoma.

From January 1987 to April 1992, 34 patients had resection of bulky positive lymph nodes, detected either at the time of radical hysterectomy (n = 23) or by computed tomographic (CT) scan of the pelvis and abdomen prior to radiation therapy for more advanced cervical cancer (n = 11). Following nodal resection, 33 patients received pelvic external beam radiation, 28 received pelvic and para-aortic radiation, and 23 received four cycles of cisplatin chemotherapy. The median number of resected positive nodes was 4, with a range of 1-44. All macroscopic nodal metastases could be resected in each patient and morbidity was acceptably low. Positive nodes were confined to the pelvis in 17 patients, involved the common iliac group in nine patients, and involved the para-aortic area in eight patients. With a mean follow-up of 36 months, 23 patients (67.6%) were alive, of whom 20 were free of disease. For patients having a radical hysterectomy, actuarial 5-year survival was 80% for patients with disease involving pelvic and common iliac lymph nodes, and 48% for those with positive para-aortic nodes. Survival for patients with completely resected bulky pelvic and common iliac nodes was comparable to that for patients with micrometastases. This study suggests that every effort should be made to identify patients with cervical cancer who have bulky positive lymph node metastases, and to remove these nodes surgically prior to radiation therapy.

Tamoxifen in patients with advanced epithelial ovarian cancer.

Tamoxifen was administered to 30 patients with persistent or recurrent epithelial ovarian cancer following initial plantinum-based chemotherapy. Two complete remissions (lasting 41 months and 12 months, respectively) were documented (6.6%), while 10 patients (33.3%) had stabilization of disease for a mean duration of 11.5 months. Tamoxifen was not associated with any significant toxicity and is a reasonable therapeutic option for patients with persistent or recurrent ovarian cancer, although it is only associated with modest activity. This paper reviews our experience with tamoxifen and summarizes the world literature.

Uterine papillary serous carcinoma. A clinical study.

BACKGROUND: Uterine papillary serous carcinoma (UPSC) is a histologic subtype of endometrial adenocarcinoma that is characterized by its papillary architecture, poor differentiation, and advanced stage at initial presentation. It behaves more aggressively than the more common endometrioid adenocarcinoma of the endometrium. METHODS: The history, treatment and follow-up of 18 women with UPSC were evaluated. RESULTS: All women underwent total hysterectomy and bilateral salpingoophorectomy. Positive lymph nodes were found in 6 of 14 patients who underwent pelvic lymphadenectomy. Twelve of 18 women with UPSC had FIGO Stage III and IV tumors in contrast to 30 of 236 patients with endometrioid adenocarcinoma (P < 000.1). Subsequent treatment of these women was: radiotherapy, three women; chemotherapy, four, both radiotherapy and chemotherapy, eight. Chemotherapy consisted of cisplatin/carboplatin plus cyclophosphamide. None of the patients with Stage I or II UPSC died of tumor during a mean follow-up of 31.6 months (range, 12-68 months). Of the women with Stage III and IV disease, 4 of 12 are alive with no evidence of disease after a mean follow-up of 22.5 months (range, 8-45 months). Eight of 12 women who received chemotherapy are alive with no evidence of disease, 4 of whom had Stage III or IV disease. One of six women who did not receive chemotherapy is alive, three died of tumor, and two of intercurrent disease. CONCLUSION: These results would justify further study of the possible role of platinum-based chemotherapy in patients with uterine papillary serous carcinoma.

Gynaecological care of women with abnormal Pap smears: how varied is current practice?

OBJECTIVE: To assess the current management by gynaecologists of women with abnormal Papanicolaou (Pap) smears. DESIGN: Self-administered survey of all gynaecologists registered in New South Wales. RESULTS: 242 gynaecologists (73% response rate) returned completed questionnaires. Accredited laboratories were used by 90% of gynaecologists, but only 61% could confirm their laboratories' participation in quality assurance procedures. Consensus on the management of high grade Pap smear abnormalities was confirmed. In contrast, there was considerable variation in the management of minor lesions, provision of patient information and follow-up after treatment. A small but worrying minority of respondents indicated an apparent misunderstanding of important colposcopic principles: 41% were prepared to institute ablative therapy without histological diagnosis. CONCLUSIONS: Given the nature of practice variation documented in this survey, publication of national guidelines is necessary to improve the screening program. Guidelines in themselves, however, will not be sufficient to ensure that all women with abnormal results of Pap smears receive appropriate and timely management and follow-up. Active dissemination to reduce undesirable variation is required.

Cervical carcinoma after negative Pap smears: evidence against rapid-onset cancers.

Recently, suggestions have been made that a 'rapid-onset' type of cervical cancer is emerging. Evidence for this entity is based on the diagnosis of invasive cervical carcinoma within 2 or 3 years of a 'normal' Pap smear. Analysis of 237 patients presenting to our unit between November 1986 and July 1990 with the histologic diagnosis of invasive carcinoma of the cervix revealed 51 patients (21.5%) who reported having had a 'normal' Pap smear within 2 years of diagnosis. Strenuous efforts were made to verify and retrieve these smears in an attempt to isolate a group of 'rapid-onset' cancers. Despite the patients' claim to the contrary, there was no record of a smear being performed in 15 patients (29%). The slides of six patients could not be located either due to lack of laboratory co-operation or because the slides had been destroyed: four of these patients had very early adenocarcinomas. The slides of 30 patients were retrieved and reviewed: 16 slides reported as negative contained cells consistent with either invasive carcinoma or carcinoma in-situ; four cases had virtually no cellular material on the slide; four cases contained atypical cells but requests for further material were not followed-up. Six patients had previously been treated for pre-invasive lesions over a range of 3-18 years. We found no case of invasive carcinoma in a patient with a confirmed adequate negative smear within 2 years of diagnosis. At most, six patients (2.52%) could have had 'rapid-onset' cancers but this could not be confirmed as these slides could not be reviewed. In summary, this study suggests that in our patient population, 'rapid-onset' cervical carcinoma is rare.

The Papanicolaou smear histories of 237 patients with cervical cancer.

OBJECTIVE: This study looks at the Papanicolaou (Pap) smear histories of patients presenting with invasive cervical cancer, to assess the problems associated with the cervical cancer screening program within New South Wales. DESIGN: Prospective collection of data concerning the Pap smear history, age, menopausal status and stage of disease of patients presenting with invasive cervical cancer. SETTING: All patients with primary invasive cervical cancer referred to the Gynaecological Oncology Department of the Royal Hospital for Women, Paddington, between November 1986 and July 1990 were included in the analysis. RESULTS: Eighty-three out of 237 patients (35%) reported never having had a Pap smear taken. These patients were on average older, more frequently postmenopausal and presented with more advanced stage of disease than the rest of the population. Fifty-one patients (21.5%) stated that they had had a "normal" smear within two years. Further analysis revealed that mistaken patient recall of the date of the last Pap smear and false-negative cytological reporting were the major factors explaining these latter cases. CONCLUSION: For voluntary screening to be more effective, quality control of cytology laboratories needs to be carefully evaluated and general practitioners need to take a more active role in cancer screening. In order to reach a greater proportion of the population, a national or State cytology register should be established.