Vulvar cancer: the Cinderella of gynaecological oncology.

Cancer of the vulva is a rare malignancy that increases progressively with age. The age-standardized incidence averages between 1 and 2 per 100,000 women in Western countries. The majority (80-90%) are squamous cell carcinomas, melanoma and adenocarcinoma each accounting for about 5% of cases. Internationally, the incidence of vulvar cancer varies more than 30-fold, the highest rates being seen in populations of Portuguese South America. In many populations the incidence appears to be stable but there is some evidence that the incidence of in situ carcinoma is increasing in the United States of America. Epidemiological studies have identified sexual factors, particularly human papilloma virus (HPV) infection, as increasing risk. Smoking also increases risk by interacting synergistically with HPV infection and genital warts. The aetiologies of vulvar intraepithelial neoplasia (VIN)3/in situ disease and invasive cancer appear to differ. VIN does not automatically progress to invasive cancer and is strongly associated with HPV infection. Many older women with invasive vulvar cancer do not have evidence of HPV and do not smoke. More research is needed on the cause of vulvar carcinoma in this group. Treatment has become more conservative over the years and this has reduced morbidity and probably mortality. Although FIGO data do not show much by way of improvement in survival, data from population-based cancer registries have shown definite increases in survival (5-year survival proportions in excess of 80%, when age and Stage have been taken into account). Improvement is particularly related to the preponderance of early stage disease.

Endometrial cancer: trends in incidence and survival: a preventable disease?

Endometrial cancer is the commonest gynaecological cancer. Its relative increase in incidence over recent decades has been generally associated with a reduction in mortality. Evidence is presented to show a considerable variation in incidence worldwide; Australia, like England and Wales, has a comparatively low incidence. The incidence is highest in parts of the United States where it has shown an annual fall of nearly 3% between 1973 and 1987. The influence of hysterectomy, oral contraception and hormone replacement therapy at the menopause are discussed relative to incidence and prevention of the disease. Obesity and its prevention are also shown to have an influence on incidence and its ethnic variation worldwide. Despite a minor improvement in survival in FIGO published figures, the recent COSA-UK-NZ 'high risk' trial highlights the importance to the patient of closely monitored clinical trials.

Pathology of the vulva.

Increasing agreement is being reached among the International Society for the Study of Vulvar Disease, the International Society of Gynecological Pathologists, the World Health Organization, and the International Federation of Gynecology and Obstetrics concerning the terminology used to describe the abnormalities of and surgical procedures for vulvar disease. This paper focuses on Paget's disease of the vulva, which is beset with recurrence and a higher incidence of invasive disease than previously recognized, although diagnostic methods have improved. Agreements on the definition for and measurement of superficially invasive squamous cell carcinoma of the vulva have also been reached. The prognostic features of tumors likely to be associated with nodal metastases are being delineated with a view to the use of conservative surgery. The risks in underestimating a tumor's capacity to metastasize are emphasized.

Adjunctive and therapeutic progestins in endometrial cancer.

With the arrival of progestin therapy for advanced, metastatic and recurrent endometrial cancer a quarter of a century ago, came the discovery that approximately one-third of all these tumors would show a clinical response. Probably no more than half of this group will survive more than 5 years. Identification of the type of patient who is most likely to respond has proven difficult. Both clinical and histopathological characteristics act only as an unreliable guide. The site of metastasis and the time for a recurrence to appear are the most constant of these factors. It is hoped that the steroid receptor content of the tumor will prove to be as valuable as it has been in the case of breast cancer. At the moment this is under investigation with numerous ongoing studies. Type, dosage and mode of administration of progestin do not appear to be critical factors in tumor response, nor does the type of synthetic agent used. However, medroxyprogesterone has been the subject of numerous symposia and is the best researched. It also offers the opportunity of being administered orally and in large doses. All agents are virtually free of toxic effects and cessation on this basis is unusual. For patients with tumors that either do not respond to progestin, or else have a temporary response, other agents--antiestrogens and cytotoxic--may well prove to be of value either simultaneously or sequentially. These possibilities are under current investigation. The definitive therapy of primary 'nonadvanced' disease is not established and is at this point unproven in any significant published randomized study. Orthodox proven methods of treatment, i.e. surgery and irradiation, must form the initial component in every patient's therapy, whatever the stage of the disease. It is hoped that prospective studies will elucidate the place of progestins in an adjunctive primary setting. However, it must be emphasized that such studies must concentrate on 'high-risk' patients. The probability of proof in any group of 'good prognosis' patients--whatever the numbers entered--appears to be very low.

Hydatidiform mole in Victoria: aetiology and natural history.

A retrospective study was made of 455 patients referred to the Hydatidiform Mole Register of the Royal Women's Hospital from 1973-1982 who fulfilled the criteria for diagnosis of hydatidiform mole. The incidence of hydatidiform mole was 1:1,357 livebirths in Victoria. Age greater than 40 years (P less than 0.001), nulliparity (P less than 0.005) and parity greater than 4 (P less than 0.001) were the only predisposing factors found. An association with artificial insemination with donor semen was also noted (P less than 0.025). The need for further treatment for persistent trophoblastic activity (13.6% of patients) was independent of the method of evacuation employed and of gestation at evacuation. Only 2 cases of histologically proven postmolar choriocarcinoma occurred, one of which was also the only death recorded from all patients registered following a molar pregnancy.

Malignant sequelae of molar pregnancy in Victoria.

In a retrospective study of 455 patients with confirmed molar pregnancy, registered with the Hydatidiform Mole Register of the State of Victoria in the years 1973-1982 inclusive, treatment for persistent trophoblastic activity was necessary in 62 (13.6%) patients. The need for treatment was independent of levels of urinary chorionic gonadotrophin (UCG) excretion prior to evacuation of the molar pregnancy, age, parity or blood group. All patients achieved initial remission of UCG levels within 5 courses of treatment. Risk factors were scored retrospectively and patients responded poorly if therapy inappropriate to risk factors was given. Only 2 cases of histologically proven choriocarcinoma occurred and the only death recorded was in 1 of these patients.

Progression of squamous carcinoma in situ of the vulva to invasive carcinoma after systemic bleomycin therapy.

Progression of squamous carcinoma in situ of the vulva to invasive carcinoma, in the same area, after systemic Bleomycin therapy, is described. Such progression is an exception and not the rule in the natural history of this disease. Conservative therapy should be used, especially in young women.

The current status of surgery for endometrial carcinoma: facts and fantasy.

Surgery is the prime method of therapy for endometrial carcinoma. However, in nearly all cases radiotherapy is combined with it either before or after operation. High risk factors include hyperoestrinism, cervical spread, myometrial invasion, cellular anaplasia, and metastatic spread to adnexa, vagina and the pelvic lymph nodes. The latter involvement of the last factor is analysed in some detail, on the base of 216 dissections with an incidence of 8%. Analysis of other authors' findings are reviewed on the basis of autopsy and selection. The place for Wertheim hysterectomy is discussed, also vaginal hysterectomy and the timing of surgery when irradiation is given preoperatively. The author's statistics are derived from a previous study of 468 patients treated between 1956 and 1971.

Endometrial carcinoma in gonadal dysgenesis with and without estrogen therapy.

PIP: 2 cases of endometrial carcinoma arising in patients with gonadal dysgenesis are reported. A 29-year-old woman originally presenting with menorrhagia was found to have developed Grade 1 adenocarcinoma 5 years later. The patient showed some features of Turner's syndrome, and analysis of blood lymphocytes revealed chromosomal mosaicism. Total hysterectomy and salpingo-oophorectomy were performed, and an extensive adenosquamous tumor was found. The patient has shown no evidence of tumor recurrence for 13 years. A 2nd patient, presenting with menorrhagia at 21 years of age, was found to have focal adenomatous hyperplasia Grade 2 within a year. She was placed on cyclic hormone therapy. 6 years after 1st examination Grade 1 adenocarcinoma with squamous metaplasia was diagnosed and removed by hysterectomy with wedge resection of the ovaries. This patient has also remained well for 7 years after the surgery. Perhaps the development of endometrial carcinoma in these cases, theoretically improbable because of the infantile uteri, is due to the high levels of unopposed endogenous estrogens. In light of this possibility, cyclic estrogen-progestogen therapy might be more appropriate than the traditional estrogen replacement therapy for treatment of cases of gonadal dysgenesis.^ieng