Chemical and Microbiological Changes of Expired Platelet Concentrate.

Background: Platelets are a commonly used blood component to prevent or treat bleeding in patients with thrombocytopenia or platelet dysfunction. They are stored at room temperature (22-24°C) for five days unless specific measures are taken to extend the shelf life to seven days or more. After five days, this study evaluated platelet units' biochemical changes and bacterial growth. Study Design and Methods: Platelet concentrate was collected from 30 random donors: 8 females and 22 males. The collected samples were then placed on an agitator at room temperature and tested for their pH, protein content, and glucose levels using Roche Combur 100 Test® Strips. The Haemonetics eBDS™ System was used for bacterial detection. The measurements were taken on day five as the control and then repeated on days 7, 9, and 11 to observe any changes. On days 5 and 7, all parameters remained unchanged. However, glucose levels significantly changed (p=<0.0001) on days 9 and 11. Regarding pH, a significant change was observed on day 9 (p=0.033) and day 11 (p=0.0002). Results: There were no significant changes in all parameters on days 5 and 7. However, glucose was substantially changed (p=<0.0001) on days 9 and 11. For pH, there was a significant change in pH on day 9 (p=0.033) and day 11 (p=0.0002). Discussions: Our study found that platelet concentrate extension is possible for up to seven days. However, further studies are needed to evaluate platelet function during expiry time and to assess the stability of platelet morphology and function.

Human immunodeficiency virus testing in patients with invasive cervical carcinoma: a prospective trial of the gynecologic oncology group.

To determine the frequency of positive human immunodeficiency virus (HIV) serostatus among North American women 50 years of age or younger with invasive cervical cancer and to define their tolerance to treatment. Consenting patients with newly diagnosed invasive cervical cancer, age 50 or younger were tested by enzyme-linked immunosorbent assay. The study design anticipated that approximately 3% of patients would be HIV positive. After the accrual of 913 eligible and evaluable patients, interim analysis revealed that only 9/913 ( approximately 1%) patients were HIV seropositive, indicating that it would not be feasible to achieve the study objective. The study was closed to further accrual. Between 1994 and 1997, the frequency of positive HIV serostatus among North American women with newly diagnosed cervical cancer was quite low. As a consequence, no evaluation of response to treatment or treatment tolerance can be made.

Synthetic peptides induce a cytotoxic response against human papillomavirus type-18.

OBJECTIVES: Over 90% of cervical carcinomas express human papillomavirus (HPV) E6 and E7 proteins. These unique antigens are ideal targets for the development of cytotoxic T-lymphocytes (CTL) for antitumor immunotherapy. In this study we identify peptides from HPV-18 E6 and E7 proteins that bind to HLA class I molecules. We further show that these peptides are able to induce peptide-specific CTL from an HLA-A2-positive (+) peripheral blood donor in vitro. METHODS: A computer-assisted algorithm was devised to identify peptides from HPV-18 E6 and E7 proteins that bind to HLA-A2 molecules. Peptides that were predicted to bind were synthesized and their binding activity was determined. HLA-A2(+) irradiated stimulator cells pulsed with HPV-18 peptides were incubated with HLA-A2(+) peripheral blood mononuclear cells. Cytotoxicity assays were performed to assess specific cell lysis. RESULTS: Of 295 possible sequences, the computer-assisted algorithm predicted 10 peptides that would have a high probability of binding to HLA-A2. The 4 strongest binding peptides were analyzed for their ability to induce cytotoxic cells against HPV-18 peptide-pulsed targets. Two of the peptides induced significant lysis. CONCLUSIONS: There are limited data on peptide-based immunotherapy for HPV-18(+) tumors. The combination of our computer-assisted algorithm and binding assay permits rapid selection of potential CTL epitopes. We identified two peptides that were able to induce peptide-specific lysis. These two epitopes are candidates for a peptide-based vaccine against HPV-18(+) tumors. The model described has broad applications and can be used in the development of immunotherapy for other types of cancers.

Vaginal 5-fluorouracil for high-grade cervical dysplasia in human immunodeficiency virus infection: a randomized trial.

OBJECTIVE: To compare the efficacy and toxicity of topical vaginal 5-fluorouracil (5-FU) maintenance therapy against the effects of observation after standard treatment for high-grade cervical dysplasia in human immunodeficiency virus (HIV)-infected women and to evaluate the association between baseline CD4 count and time to recurrence. METHODS: In a phase III unmasked, randomized, multicenter, outpatient clinical trial, 101 HIV-positive women either received 6 months of biweekly treatment with vaginal 5-FU cream (2 g) or underwent 6 months of observation after standard excisional or ablative cervical treatment for cervical intraepithelial neoplasia (CIN). Papanicolaou smears and colposcopy were scheduled at regular intervals during the ensuing 18 months, with the primary end point being the time at which CIN of any grade recurred. RESULTS: Thirty-eight percent of women developed recurrence: 14 (28%) of 50 in the 5-FU therapy group and 24 (47%) of 51 in the observation group. Treatment with 5-FU was significantly associated with prolonged time to CIN development (P = .04). Observation subjects were more likely to have high-grade recurrences, with 31% developing CIN 2-3 compared with 8% in the 5-FU treatment arm (P = .014), and disease recurred more quickly in observation subjects as well. Baseline CD4 count was related significantly to time to recurrence (P = .04), with 46% of subjects with CD4 counts less than 200 cells/mm3 developing recurrence compared with 33% of subjects with CD4 counts at least 200 cells/mm3. Disease recurred more slowly in subjects who had received antiretroviral therapy than in antiretroviral therapy-naive subjects. There were no instances of grade 3 or 4 toxicity, and compliance with 5-FU treatment was generally good. CONCLUSION: Adjunctive maintenance intravaginal 5-FU therapy after standard surgery for high-grade lesions safely and effectively reduced recurrence of cervical intraepithelial neoplasia in HIV-infected women.

Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer.

BACKGROUND AND METHODS: On behalf of the Gynecologic Oncology Group, we performed a randomized trial of radiotherapy in combination with three concurrent chemotherapy regimens -- cisplatin alone; cisplatin, fluorouracil, and hydroxyurea; and hydroxyurea alone -- in patients with locally advanced cervical cancer. Women with primary untreated invasive squamous-cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix of stage IIB, III, or IVA, without involvement of the para-aortic lymph nodes, were enrolled. The patients had to have a leukocyte count of at least 3000 per cubic millimeter, a platelet count of at least 100,000 per cubic millimeter, a serum creatinine level no higher than 2 mg per deciliter (177 micromol per liter), and adequate hepatic function. All patients received external-beam radiotherapy according to a strict protocol. Patients were randomly assigned to receive one of three chemotherapy regimens: 40 mg of cisplatin per square meter of body-surface area per week for six weeks (group 1); 50 mg of cisplatin per square meter on days 1 and 29, followed by 4 g of fluorouracil per square meter given as a 96-hour infusion on days 1 and 29, and 2 g of oral hydroxyurea per square meter twice weekly for six weeks (group 2); or 3 g of oral hydroxyurea per square meter twice weekly for six weeks (group 3). RESULTS: The analysis included 526 women. The median duration of follow-up was 35 months. Both groups that received cisplatin had a higher rate of progression-free survival than the group that received hydroxyurea alone (P<0.001 for both comparisons). The relative risks of progression of disease or death were 0.57 (95 percent confidence interval, 0.42 to 0.78) in group 1 and 0.55 (95 percent confidence interval, 0.40 to 0.75) in group 2, as compared with group 3. The overall survival rate was significantly higher in groups 1 and 2 than in group 3, with relative risks of death of 0.61 (95 percent confidence interval, 0.44 to 0.85) and 0.58 (95 percent confidence interval, 0.41 to 0.81), respectively. CONCLUSIONS: Regimens of radiotherapy and chemotherapy that contain cisplatin improve the rates of survival and progression-free survival among women with locally advanced cervical cancer.

Management of cervical neoplasia in human immunodeficiency virus-infected women.

The existence of cervical neoplasia in women with human immunodeficiency virus (HIV) represents one of the most serious challenges in the oncologic care of immunosuppressed patients. While the development of most cancers in the immunosuppressed patient can be attributed solely to immune deficiency, the relationship between squamous cell neoplasia of the cervix and HIV is quite unique because of common sexual behavioral risk factors. Screening strategies in HIV-positive women must take into account the high prevalence of cervical dysplasia in this subgroup as well as the limitations of cytologic screening. Cervical dysplasia in HIV-positive women may be of higher grade than in HIV-negative patients, with more extensive involvement of the lower genital tract with HPV-associated lesions. The presence and severity of cervical neoplasia in HIV-positive women correlate with both quantitative and qualitative T-cell function. Standard therapies for preinvasive cervical disease have yielded suboptimal results with high recurrent rates. While poor treatment results of standard ablative and excisional therapies warrant unique therapeutic strategies, one must recognize that close surveillance and repetitive treatment have been successful in preventing progressive neoplasia and invasive cervical carcinoma. The disease characteristics of invasive cervical carcinoma may take a more aggressive clinical course in HIV-infected women. HIV-positive women with cervical cancer have higher recurrence and death rates with shorter intervals to recurrence and death than do HIV-negative control subjects. CD4 status does influence subsequent outcome. In general, the same principles that guide the oncologic management of cervical cancer in immunocompetent patients should be applied. However, extremely close monitoring for both therapeutic efficacy and unusual toxicity must be instituted.

Is HIV infection a risk factor for advanced cervical cancer?

OBJECTIVES: To compare HIV-infected and HIV-negative women with invasive cervical cancer with respect to predictors of advanced disease. METHODS: A retrospective analysis of 28 HIV-positive and 132 HIV-negative women with invasive cervical carcinoma was conducted and the two groups were compared with regard to stage of disease, demographic and behavioral variables, and risk factors for advanced disease. RESULTS: Overall, HIV-infected women were more likely to have advanced disease, because 78% of HIV-positive women had Stage II to IV compared with 55% of HIV-negative women (odds ratio [OR] = 3.1; p = .03). Substance abuse was strongly associated with HIV infection, as were high-risk sexual variables. Although HIV infection was associated with a threefold increase in advance stage cervical cancer in a univariate analysis, only symptom duration and lack of a recent Papanicolaou smear were significant predictors of advanced disease in a multiple logistic regression analysis. CONCLUSIONS: The major predictors of advanced cervical cancer are similar in HIV-positive and HIV-negative women, although the reasons for these predictors may be very different. It is likely that a large proportion of HIV-positive patients with cervical cancer acquire HIV infection after initiation of the neoplastic process.

Rapid progression to invasive cervix cancer in a woman infected with the human immunodeficiency virus.

BACKGROUND: Previous studies have shown an increased risk of cervical dysplasia in women infected with human immunodeficiency virus (HIV), as well as an increased risk of progression to higher-grade lesions. It is not known whether the rate of progression is accelerated over that in immunocompetent women. CASE: During September 1991, an HIV-positive woman underwent conization of the cervix showing carcinoma in situ. The surgical margins and endocervical curettings were negative for dysplasia. Papanicolaou smears 4 and 7 months after the conization also were negative. She then presented 33 months postconization with a stage Ib2 cervical carcinoma, which proved resistant to chemotherapy and pelvic radiation. CONCLUSION: Immunosuppression caused by HIV infection may cause a more rapid progression of cervical intraepithelial lesions to carcinoma.

Prevalence, risk factors, and accuracy of cytologic screening for cervical intraepithelial neoplasia in women with the human immunodeficiency virus.

OBJECTIVES: The objective was to evaluate the sensitivity and specificity of cervical cytology in women infected with the human immunodeficiency virus (HIV), risk factors for abnormal cytology in HIV-infected and uninfected women, and risk factors for histologic diagnosis of cervical intraepithelial neoplasia (CIN) in HIV-infected women. METHODS: Methods included a cross-sectional analysis of cervical cytology, colposcopic impression, and histology in 248 HIV-infected women and multivariate analyses of risk factors for abnormal cytology in 253 HIV-infected and 220 uninfected women and risk factors for CIN in 186 HIV-infected women. RESULTS: The sensitivity and specificity of cytology for all CIN grades were 0.60 and 0.80 and, for high-grade CIN, 0.83 and 0.74. The prevalence of abnormal cytology was 32.9% in HIV-infected and 7.6% in HIV-negative women. Independent risk factors for abnormal cytology were immunodeficiency [odds ratio (OR) 8-17, P < 0.001] and human papillomavirus (HPV) infection (OR = 5, P < 0.001). The prevalence of CIN on histology was 32% in HIV-infected women, and the only independent risk factor for CIN was oncogenic HPV type (OR = 5, P = 0.005). CONCLUSION: Given the high prevalence of abnormal cytology and CIN in HIV-infected women, cytologic screening has significant limitations. Both immunodeficiency and type of HPV infection are important risk factors.

Endometriosis with massive ascites.

We present 4 cases of endometriosis complicated by massive ascites from our institution and a review of 27 cases from the literature. In most of these patients, the presence of ascites with its related symptoms in association with pelvic masses suggested a neoplastic disease. However, a large proportion of these women had also classical manifestations of endometriosis, e.g., dysmenorrhea, cul-de-sac nodularities, and exacerbation of ascites and other symptoms during the menses. The response to hormonal therapy including GnRH agonists was often unsatisfactory. Repeat recurrences and severe complications required multiple laparotomies and thoracotomies for associated pleural and pulmonary involvement.

Papillary serous and clear cell type lead to poor prognosis of endometrial carcinoma in black women.

OBJECTIVE: To investigate the significance of race and histologic type as prognostic factors in endometrial carcinoma. METHODS: We conducted a retrospective review of the medical records of all patients diagnosed with endometrial cancer from 1982 to 1995. Patients' clinical and pathologic characteristics were analyzed. RESULTS: The sample consisted of 401 patients, 59.9% (N = 229) were blacks and 40.1% (N = 153) were non-blacks. The mean age was 63.7 +/- 11.6 years. The histologic subtypes of endometrial carcinoma included 346 endometrioid (86.3%), 42 papillary serous (10.5%), and 13 clear cell (3.2%) adenocarcinomas. We found 79% of endometrioid adenocarcinomas were stage I or II compared to 26% of papillary serous tumors and 58% of clear cell carcinomas (P < 0.01). Eighty-eight percent of patients with papillary serous and 77% of patients with clear cell cancers were black (P < 0.01). Within each stage, patients were treated similarly irrespective of cell type or race. Five-year survival for endometrioid, papillary serous and clear cell adenocarcinomas was 69, 18, and 25%, respectively (P < 0.01). Black women had poorer 5-year survival (56%) than non-black women (71%). In multivariate analyses using age, stage, race, and histology, only stage and histology were independent risk factors for survival. CONCLUSIONS: Patients with papillary serous and clear cell endometrial cancer were more likely to be black, present at an advanced stage of disease, and have poor survival compared to patients with endometrioid adenocarcinoma. This may help to explain the poorer survival reported in blacks with endometrial cancer.

Neoadjuvant chemotherapy in stage IB2 squamous cell carcinoma of the cervix.

To determine the effects of neoadjuvant chemotherapy (NAC) in the management of cervical carcinoma Stage IB2 (tumor diameter > 4 cm), we reviewed 52 surgically treated patients diagnosed between January 1987 and December 1993. There were 20 patients treated with preoperative neoadjuvant chemotherapy and 32 treated by primary radical hysterectomy. Mean tumor diameter was significantly larger in the neoadjuvant, compared with the primary surgery group (6.5 +/- 1.8 vs 5.4 +/- 0.7, P = 0.003). In the NAC group, 5 of 20 patients were treated with three courses of cisplatin, methotrexate, and bleomycin every 21 days, whereas 15 of 20 patients received three courses of cisplatin, vincristine, and bleomycin every 10 days. Postoperative adjuvant therapy consisting of either radiation or chemotherapy was employed in 13/20 patients (65%) in the NAC group and 20/32 patients (63%) in the primary surgical group. At a median follow-up of 52.5 months, 4/20 patients (20%) in the NAC group recurred vs 11/32 (34%) in the primary surgery group. The overall response rate to NAC was 90%, with 2/20 complete clinical responders and 16/20 partial responders. High-risk pathologic factors were less commonly observed in the NAC group when compared with the primary surgical group with the incidence of nodal metastases, positive vascular space involvement, undiagnosed parametrial disease, and > or = 75% depth of invasion observed in 10.0% vs 37.5%, 20.0% vs 46.9%, 0.0% vs 15.6%, and 30.0% vs 68.8%, respectively. No differences were noted in operative time or blood loss. Cox proportional-hazards analysis indicated that the most significant prognostic factor was depth of invasion. Although the patients who received neoadjuvant chemotherapy had significantly larger tumors at baseline, their 5-year survival rate was slightly higher than that of the primary surgery group (80.0% vs 68.7%, P = 0.162). Patients receiving neoadjuvant chemotherapy, despite having significantly larger pretreatment tumors, had fewer high-risk pathologic factors, postoperatively. Although this was a small, nonrandomized study, the relative improvement in pathologic response and long-term outcome associated with neoadjuvant chemotherapy was encouraging. This highlights the need for a prospective randomized clinical trial to establish whether neoadjuvant chemotherapy can significantly improve the long-term outcome of women with Stage IB2 squamous cell carcinoma of the cervix.

Uterine carcinosarcomas: incidence and trends in management and survival.

Our study's aim was to determine the incidence of uterine sarcomas in New York City (NYC) and evaluate trends in frequency, treatment, and survival of carcinosarcomas in two Brooklyn hospitals. Population-based cancer registry data for 1976-1985 were used to calculate the incidence of uterine sarcomas in NYC women. Medical records and histology slides of carcinosarcomas at two central Brooklyn hospitals from 1960 to 1995 were reviewed. The incidence of uterine sarcomas in black and white women in NYC was 33.4 and 17.0 per million (P < 0.01). Among 97 women with carcinosarcomas diagnosed in 1960-1995, 75% were diagnosed preoperatively, 82% had a hysterectomy, and 45% of those in clinical stage I were upstaged. Predictors of mortality included the presence of extrauterine extension, deep myometrial invasion, vascular space invasion, and gross residual disease, with only the first two being independent predictors of survival in a multivariate analysis. Adjunctive therapy shifted from radiation in 1960-1969 to cisplatin-based chemotherapy after 1980. In surgical stage III, survival increased significantly between 1960-1979 and 1980-1995, but improvement could not be ascribed to particular therapies. The incidence of uterine sarcomas in black women was twice that in white women. Surgical staging including omentectomy is recommended in the management of carcinosarcomas. Modern medical care may have improved the short-term prognosis of carcinosarcomas.

Cervical cancer as an AIDS-defining illness.

OBJECTIVE: To evaluate the importance of cervical cancer in the spectrum of human immunodeficiency virus (HIV)-related diseases at a single high-risk institution and to compare disease characteristics in HIV-infected women with cervical cancer and those with other AIDS-related malignancies. METHODS: We retrospectively reviewed data on cervical cancer and AIDS in women registered through the New York City Department of Health and institutional tumor registries from 1987 through 1995. RESULTS: During the study period, cervical cancer was diagnosed in 28 HIV-positive women. In 26, cervical cancer was the initial AIDS-defining illness, representing 4% (26 of 725) of the subjects, and it was the sixth most common initial AIDS-defining illness in women. Cervical cancer was the most common AIDS-related malignancy among women, representing 55% of the cases, followed by lymphoma (29%) and Kaposi sarcoma (16%). In 71% of the women with cervical cancer, HIV infection was diagnosed at the time of cancer presentation by routine testing, whereas in women with other malignancies, HIV diagnosis preceded cancer diagnosis (70%) by a mean of 2.7 years. Patients with other malignancies had greater immunosuppression (mean CD4 count 153/microL) than those with cervical cancer (mean CD4 count 312/microL). The recurrence rate for women with cervical cancer was 88%. Although the interval from cancer diagnosis to death was similar in all three groups (9.1-12.4 months), cancer was the cause of death in 95% of HIV-infected women with cervical cancer, compared with 60% of those with other AIDS-related malignancies. CONCLUSION: In urban populations at increased risk for both diseases, cervical cancer is an important AIDS-defining illness and may be the most common AIDS-related malignancy in women.

Non-Hodgkin lymphoma of the endometrium in human immunodeficiency virus infection.

BACKGROUND: Non-Hodgkin lymphoma has become a common malignancy in patients infected with the human immunodeficiency virus (HIV), being classified as an acquired immunodeficiency syndrome-defining malignancy. The female genital tract is involved usually with non-Hodgkin lymphoma as part of disseminated disease. It is extremely rare for this tumor to originate in the female reproductive tract, especially in the endometrium. CASE: An HIV-positive woman underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy for intractable menometorrhagia and resultant anemia thought to be secondary to uterine leiomyoma. The histologic diagnosis was high-grade, immunoblastic, non-Hodgkin lymphoma with plasmacytoid features originating in the endometrium. CONCLUSION: This unusual presentation obligates the clinician to include non-Hodgkin lymphoma in the differential diagnosis when evaluating HIV-positive patients with abnormal uterine bleeding that cannot be explained after thorough evaluation.

Multiple recurrences of cervical intraepithelial neoplasia in women with the human immunodeficiency virus.

OBJECTIVE: To evaluate the long-term outcomes after treatment of cervical intraepithelial neoplasia (CIN) in women infected with the human immunodeficiency virus (HIV). METHODS: Human immunodeficiency virus-infected and HIV-negative women treated for CIN by ablation or excision were followed-up prospectively by cytology and colposcopy for periods of up to 73 months. RESULTS: Among 127 HIV-infected CIN patients, 62% developed recurrent CIN by 36 months after treatment, compared with 18% of the 193 HIV-negative CIN patients. Recurrence rates reached 87% in 41 HIV-infected women with CD4 counts less than 200 cells/mm3. Progression to higher-grade neoplasia, including one invasive cancer, occurred by 36 months in 25% of HIV-infected and 2% of HIV-negative women. After adjusting for age, CIN severity, and treatment type, predictors of recurrence included HIV infection (rate ratio 4.4), and, in HIV-positive women, low CD4 count (rate ratio 2.2). In patients treated by excision, predictors of recurrence included HIV infection (rate ratio 2.0) and residual CIN after treatment (rate ratio 2.7). After a second treatment,a second CIN recurrence developed in 14 of 33 HIV-infected and in one of 17 HIV-negative women. After a third treatment, three of six HIV-infected women developed a third recurrence. With long-term follow-up, 45% of treated HIV-infected CIN patients had chronic condylomatous changes in the cervix compared with 5% of HIV-negative women. CONCLUSION: In HIV-infected women, CIN may recur despite multiple treatments, and chronic condylomatous changes are common. Innovative therapies for controlling CIN in HIV-infected women are needed.

Ovarian cancer after successful ovulation induction: a case report.

BACKGROUND: Questions have been raised regarding the potential association of ovulation-inducing drugs and ovarian cancer. Worldwide there have been 13 cases of ovarian carcinoma reported to occur in women previously treated with ovulation-inducing drugs (clomiphene citrate and/or gonadotropins). CASE: A 40-year-old woman complained of secondary infertility. She conceived after five cycles of human menopausal gonadotropins with intrauterine insemination. Eight months after cesarean delivery, she presented with right lower quadrant pain and a right adnexal mass. At exploratory laparotomy the patient was found to have a poorly differentiated papillary serous carcinoma of the ovary. CONCLUSION: Ovarian carcinoma developed within 18 months of exposure to ovulation-inducing agents, human menopausal gonadotropins. It would be prudent to gather a registry of cases to assess the risk associated with human menopausal gonadotropins with or without gonadotropin-releasing hormone analogs.

Complications after treatment of cervical intraepithelial neoplasia in women infected with the human immunodeficiency virus.

OBJECTIVE: To compare the frequency of complications after treatment of cervical intraepithelial neoplasia (CIN) in human immunodeficiency virus (HIV)-infected and -seronegative women in an ambulatory setting. STUDY DESIGN: A retrospective record review of 15 HIV-infected and 44 HIV-negative women treated by laser therapy or cone biopsy and retrospective interviews of 20 HIV-infected and 44 HIV-negative women treated by cryotherapy. RESULTS: Four of 35 (11%) HIV-infected women had excessive bleeding after laser/cone or cryotherapy as compared to one of 88 (1%) HIV-negative women (odds ratio 11.27, P = .02). After laser/cone therapy, significantly more HIV-infected women (53%) had cervicovaginal infections than did HIV-negative women (18%). A higher prevalence of infection was associated with more severe immunodeficiency. CONCLUSION: HIV-infected women are vulnerable to complications after treatment of CIN and should be monitored closely.

CD4 lymphocytes in women with invasive and preinvasive cervical neoplasia.

OBJECTIVE: To assess the relationship between CD4 lymphocyte population and stage of disease in cervical neoplasia. METHODS: Study population was 107 women with invasive cervical cancer, 116 women with cervical intraepithelial neoplasia (CIN), and 32 women without neoplasia diagnosed in 1988-1994. All women under age 50 were seronegative for the human immunodeficiency virus (HIV). All women over age 50 with CD4:CD8 ratio below normal were HIV-negative. Stage was defined by FIGO criteria using clinical findings. CD4 and CD8 lymphocyte populations were enumerated by flow cytometry prior to treatment. The normal range of CD4 counts was defined as 537-1571 cells/mm3. RESULTS: Distribution of CD4 count was similar in stages I (n = 40), II (n = 24), and III (n = 32), with 31% below normal and 9% above normal (mean CD4 count = 881). However, in stage IV (n = 11), 64% were below normal and 18% above normal (mean CD4 = 591). The difference in distribution between stages I-III and stage IV was statistically significant. Among 116 CIN patients, 10% had CD4 counts below normal and 3% above normal (mean CD4 = 910). Among 32 women without cervical neoplasia, 0% had CD4 counts below normal and 3% above normal. The difference between CIN and invasive cancer in the distribution of CD4 counts and CD8 counts was significant (P < 0.01). There was no difference in the CD4 count distribution by CIN severity. Forty-five percent of patients with below-normal CD4 counts at diagnosis developed recurrent cancer compared to 43% of patients with normal or above-normal CD4 counts. CONCLUSION: Women with invasive cervical cancer have lower CD4 counts and a broader distribution compared to women with preinvasive or no neoplasia. Metastatic cancer at diagnosis was associated with severely depressed CD4 count.

Phase II trial of mitomycin-C in squamous cell carcinoma of the uterine cervix: a Gynecologic Oncology Group study.

Fifty-six patients with advanced, persistent, or recurrent squamous cell carcinoma of the cervix not previously exposed to cytotoxic drugs, other than as radiosensitizers, were entered into a study of single-agent 20 mg/m2 mitomycin-C every 6 weeks. The overall response rate among the 52 patients evaluable for response was 12% (three complete and three partial responses). Median response duration was 7.3 months. For the entire population, median progression-free interval was 3.0 months, and median survival was 4.9 months. Among 27 patients with pelvic disease only in previously radiated fields, two responses were observed (7%), whereas four responses were observed among 25 patients with extrapelvic disease in nonradiated fields (16%). The most frequent and severe adverse effects were the result of myelosuppression. Based on the modest level of activity observed, no further study of mitomycin-C in squamous cell carcinoma of the cervix is planned.