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Immunotherapy using the streptococcal preparation OK-432 for the treatment of uterine cervical cancer. Cervical Cancer Immunotherapy Study Group.

The efficacy of immunotherapy using a streptococcal preparation, OK-432, was evaluated in each clinical stage of uterine cervical cancer. The 382 eligible patients were stratified by clinical stage and presence/absence of surgery. Within each stratum, patient's were randomly allocated to OK-432 treatment or to control treatment. OK-432 significantly inhibited recurrence in patients with stage II cervical cancer; the recurrence-free interval and survival time were remarkably prolonged in patients with stage II disease who underwent surgery. However, OK-432 did not significantly prolong these parameters in patients with stage III disease. Retrospective analyses revealed that in patients with or without lymph node metastases who underwent surgery, the recurrence-free interval and survival time were significantly prolonged by OK-432 treatment. These results indicate that OK-432 is an effective and useful postoperative immunotherapeutic agent for uterine cervical cancer.

Biological Products

Immunotherapy using the streptococcal preparation OK-432 for the treatment of uterine cervical cancer. Cervical Cancer Immunotherapy Study Group.

The effectiveness of immunotherapy using a streptococcal preparation, OK-432, was evaluated for cervical cancer. The 382 eligible patients were stratified by presence/absence of surgical operation and clinical stage, and then, in each stratum, were randomly divided into two groups: an OK-432 treatment group and a control treatment group. The 3-year recurrence-free rates of 221 patients in the OK-432 group and 161 patients in the control group were 71.9% and 58.6%, respectively. The intergroup difference was statistically significant (P less than 0.05). Delayed skin reactions to phytohemagglutinin (PHA) and Su-polysaccharide extracted from Streptococcus pyogenes Su-strain (Su-PS) and peripheral lymphocyte counts were reduced within two months after the initiation of therapy in both groups. The observed immunological changes were apparently reversed by 3 months after the start of the therapy in the OK-432 group, but this took at least one year in the control group, with significant intergroup differences at 6 and 12 months of the therapy (P less than 0.01). These results indicate that OK-432 can be considered as one of the most effective and useful immunotherapeutic agents for cervical cancer.

Biological Products

Randomized trial of epirubicin and cisplatin chemotherapy followed by pelvic radiation in locally advanced cervical cancer. Cervical Cancer Study Group of the Asian Oceanian Clinical Oncology Association.

PURPOSE: Pelvic radiation is standard treatment for women with stage IIb to IVa cervical cancer, but treatment results are disappointing, particularly for women with bulky tumors. We investigated the role of primary chemotherapy followed by pelvic radiotherapy in a randomized trial. PATIENTS AND METHODS: Two hundred sixty patients with stage IIb and IVa cervical cancer received either standard pelvic radiotherapy or primary chemotherapy with cisplatin 60 mg/m2 and epirubicin 110 mg/m2 administered at 3-week intervals for three cycles, followed by pelvic radiotherapy. RESULTS: Ninety-nine patients have relapsed with a median follow-up duration of 1.3 years; in 62 patients, the first site of progressive disease was the pelvis. Patients who received primary chemotherapy had a significantly higher pelvic failure rate than those who received radiotherapy alone (P < .003). Seventy-six patients have died, and those who received primary chemotherapy had significantly inferior survival compared with those who received radiotherapy alone (P = .02). Tumor response following chemotherapy was observed in 63%. After radiotherapy, tumor response occurred in 72% of those who received combined modality treatment, compared with 92% of those who received radiotherapy alone. CONCLUSION: Primary chemotherapy with epirubicin and cisplatin, although resulting in tumor response in a significant proportion of patients, is accompanied by an inferior local control rate and survival compared with standard pelvic radiotherapy alone.

Adenocarcinoma

Endometrial cancer, cervical cancer, and the adnexal mass.

Cancers of the endometrium, cervix, and ovaries account for nearly 25,000 annual deaths among women in the United States. In recent years, better understanding of the causes and risk factors associated with gynecologic malignancies has contributed to more effective screening and early diagnosis. Abnormal uterine bleeding, a palpable adnexal mass, or vague abdominal complaints in women older than 40 can be signs of cancer. Regular pelvic examination, combined with appropriate use of the Papanicolaou's smear, endometrial biopsy, transvaginal sonography, and other tests, is recommended.

Aftercare

[The general criteria and recommendations for the elaboration of programs for the early detection of breast cancer and cervical cancer in Spain. The Working Group for the Early Detection of Breast Cancer and Cervical Cancer].

Cancer screening and primary prevention of cancer are effective strategies to reduce cancer morbidity and mortality. The experience gained in several European countries about breast and cervical cancer has been growing in the last decades. This fact facilitates the adoption of the most convenient strategies to implement screening programmes in Spain. The Spanish Ministry of Health and Consumer Affairs set up a work group of experts and health managers to make recommendations and to define the basic criteria to take into account when planning and implementing these programmes. The article describes those recommendations as well as the priorities to be established regarding the target population, and the strategies to increase efficiency of those programmes. Recommendations were made according with scientific evidences and the current situation and resources in Spain.

Breast Neoplasms

New approaches to high-risk cervical cancer. Advanced cervical cancer.

BACKGROUND: The role of chemotherapy in the surgical management of high-risk cervical cancer has not yet been defined. Based on the ability of numerous cytotoxic agents to induce regressions in advanced and recurrent cervical cancer, there is now a trend toward early use of these drugs. The efficacy of cisplatin-containing regimens in particular suggests that new strategies combining chemotherapy and surgery may result in improved survival rates in patients with high-risk cervical cancer. METHODS: In this review of the literature, two groups of patients who may benefit from this approach to therapy are discussed. In the first group are patients with local or regionally advanced cervical carcinoma who receive chemotherapy (neoadjuvant) with the goal of reducing tumor bulk and thus allowing surgical treatment in normally inoperable cases. The second group consist of patients with identifiable adverse risk factors after radical hysterectomy and pelvic lymphadenectomy who receive postoperative chemotherapy (adjuvant) in an effort to decrease local and distant recurrences. RESULTS: The administration of neoadjuvant chemotherapy to patients with local and locally advanced cervical cancer allows radical surgery to be performed in many patients who otherwise would be considered inoperable. In these patients, there also appears to be a decrease in the incidence of pelvic and distant recurrences and possibly an improvement in survival rates. Adjuvant chemotherapy after radical surgery for patients at high risk for recurrence appears to provide a survival advantage in some high-risk patients. CONCLUSIONS: Preliminary results in the new approaches to therapy that combine chemotherapy with surgery in patients with high-risk cervical cancer are encouraging. Randomized prospective trials are warranted to identify the most active chemotherapeutic regimens and to determine the patient selection criteria most likely to result in improved survival rates.

Antineoplastic Combined Chemotherapy Protocols

Antibodies against early proteins of human papillomaviruses as diagnostic markers for invasive cervical cancer.

Cervical cancer is the most prevalent tumor in developing countries and the second most frequent cancer among females worldwide. Specific human papillomaviruses (HPVs) and, most notably, HPV types 16 and 18 are recognized as being causally associated with this malignancy. Antibodies against early HPV proteins E6 and E7 have been found more often in patients with tumors than in controls. Existing peptide enzyme-linked immunosorbent assays (ELISAs) for the detection of anti-E6 and anti-E7 antibodies in human sera have low levels of sensitivity and specificity and thus are not suitable for use as diagnostic tools. Based on highly purified recombinant native proteins, we developed four sandwich ELISAs for the detection of antibodies against HPV type 16 and 18 E6 and E7 proteins. We demonstrate their sensitivities and high degrees of specificity for cervical cancer. Among a total of 501 serum specimens from unselected patients with invasive cervical cancer, 52.9% reacted positively in at least one of the four assays. In contrast, among 244 serum specimens from control subjects without cervical cancer, only 2 reactive serum specimens (0.8%) were found. For 19 of 19 antibody-positive patients, the HPV type indicated by seroreactivity was identical to the HPV DNA type found in the tumor, which also indicates a high degree of specificity for antibody detection with respect to HPV type. In a direct comparison of 72 serum specimens from patients with cervical cancer, 56% of the specimens reacted in at least one of the four protein ELISAs, whereas 40% reacted in at least one of seven peptide ELISAs covering the four antigens. These assays could be of value for the detection of invasive cervical cancer in settings in which cytology-based early tumor screening is not available, for the clinical management of patients diagnosed with cervical cancer, and for the immunological monitoring of E6 and E7 vaccination trials.

Adult

Epidemiology of genital papillomaviruses and cervical cancer.

Cervical cancer is an extremely common disease. Its natural history has been well described, and individual risk factors have been defined. It is clear from the epidemiologic evidence that cervical cancer has a multifactorial etiology involving infection with sexually transmitted agents such as genital papillomaviruses and cofactors such as pregnancy, smoking, use of hormonal contraceptives, and diet. The evidence implicating papillomavirus as an etiologic agent of cervical cancer has come from a variety of observational laboratory studies. Genital papillomaviruses induce dysplastic lesions. Most invasive cervical cancers contain papillomavirus DNA, as do cell lines derived from cervical cancers. Viral DNA, appears to be integrated into cellular DNA, and integration involves highly conserved, transcriptionally active regions of the viral DNA.

Age Factors

The presence of human papillomavirus-16/-18 E6, p53, and Bcl-2 protein in cervicovaginal smears from patients with invasive cervical cancer.

Cervical cancer is the second leading cause of death from cancer in women worldwide, and recent epidemiological studies have strongly implicated the sexually transmitted human papillomavirus (HPV) as a causative agent. The ability of high-risk HPVs to contribute to malignant progression seems to depend on expression of the viral E6 and E7 oncogenes. The E6 oncoprotein forms a complex with the cellular tumor suppressor protein p53, leading to degradation of p53 via ubiquitin-dependent proteolysis. Thus, E6 expression results in the loss of p53 function in cells, including stimulation of apoptosis and inhibition of the expression of the antiapoptotic protein bcl-2. Recently, we found increased bcl-2 expression in cervical carcinoma cell lines containing mutated or E6-inactivated p53 (X. L. Liang, S. Mungal, A. Ayscue, J. D. Meissner, P. Wodnicki, G. Gordon, S. Lockett, and B. Herman. J. Cell. Biochem., 57: 509-520, 1995). Based on these findings, we examined Papanicolaou smears from 94 women with varying degrees of cervical disease for the presence or absence of p53, HPV-16/18 E6, and bcl-2 proteins using immunofluorescence microscopy. Our findings indicate that there is a statistically significant, inverse association between the presence of p53 and invasive cervical disease [odds ratio (OR), 0.3; 95% confidence interval (CI), 0.1-0.7]. Moreover, the odds of being diagnosed with an invasive stage of cervical cancer were 3.7 times higher (95% CI, 1.6-8.8) for women positive for the E6 protein and 17 times higher (95% CI, 5.5-58.3) for women positive for the bcl-2 protein compared with women negative for E6 and bcl-2. Women with invasive cervical cancer were also 4.59 times more likely to test positive for the presence of more than one marker (95% CI, 1.8-11.8). Chi(2) analysis demonstrated a strong association between the presence of E6 and bcl-2 (P < 0.001) as well as between the presence of E6 of bcl-2 and diagnosis (P = 0.015 and < 0.001, respectively). In the multivariate analysis, the presence of bcl-2 (OR, 18.8; 95% CI, 5.5-67.8) and age at diagnosis (> or = 50 years; OR, 7.8; 95% CI, 2.5-24.5) showed significant association with Invasive cervical disease. These findings indicate that: (a) the presence of the bcl-2 protein is strongly associated with the development of invasive cervical disease: (b) the pattern of the presence of high-risk HPV-E6, p53, and bcl-2 proteins may be useful for identifying women at increased risk for the development of invasive cervical cancer; and (c) a defect in apoptosis may partially underlie the development of cervical cancer.

Adult

Evaluation of carcinoembryonic antigen, tissue polypeptide antigen, and squamous cell carcinoma antigen in the detection of cervical cancers.

Cervical cancer is a predomiannt gynecologic neoplasia in Taiwan. The associations of carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA) and squamous cell carcinoma antigen (SCC-Ag) for detection of cervical cancers with type of cancer, clinical stage and lymph node metastasis were studied. Serum samples were collected from 395 patients with cervical cancers (61 CIN3, 334 squamous cell carcinoma, 18 adenocarcinoma), 72 patients with benign gynecologic diseases and 115 healthy controls. The sensitivities of CEA, TPA, and SCC-Ag were 15.2%, 33.6%, and 49.3%. The specificities were 89.3%, 96.2%, and 95.1%, respectively. The positive rate of CEA was found significantly higher among patients with adenocarcinoma than those with squamous cell carcinoma. The positive rate of CEA and SCC-Ag increased with advance of the clinical stages. There was no significant difference in the rate of each tumor marker between patients with lymph node metastasis and those without metastasis. The positive rate obtained by SCC-Ag alone was comparable to those by the combinations of two or three antigens. The result of the present study indicates that SCC-Ag is the most useful tumor marker in the detection of cervical cancers.

Adenocarcinoma

Epidemiology of cervical cancer.

Cervical cancer is a major public health problem through-out the world, and despite important declines in incidence and mortality observed in developed countries in the last 20 years, those indicators remain almost unchanged in developing countries. In addition, a recent increase in cervical cancer among women under age 50 years is being observed in some areas, particularly for adenocarcinoma, without a clear explanation. Marked socioeconomic and ethnic differences are evident in incidence, mortality, and survival from the disease, with the less affluent groups having a much higher impact. Epidemiologic research has concluded that certain types of human papillomaviruses are the central cause of cervical cancer and its precursors, and this has opened the door to the possibility of developing vaccines. However, many aspects of the epidemiology still need to be elucidated, and the development of clinically applicable vaccines will require a number of years to be achieved. Therefore, renewed efforts at improving screening programs are necessary, particularly among women in the lower socioeconomic regions and groups. In this paper, we present the descriptive epidemiology of invasive cervical cancer, with particular emphasis on the situation in the United States, based on the latest data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (up to 1992). In addition, a brief overview is made of current ideas on the role of human papillomaviruses and other risk factors for the disease.

Aged

Aetiological parallel between anal cancer and cervical cancer.

It has been postulated that an infectious agent and/or specific sexual behaviour is involved in the aetiology of anal cancer, in analogy with the aetiology established for cancer of the cervix. A case-control study of 29,648 women with cancers registered in the Danish Cancer Registry during 1968-87 tested the hypothesis that anal cancer patients were more likely than patients with colon, stomach, or vulva cancer to have had a previous diagnosis of cervical intraepithelial neoplasia (CIN) or invasive cervical cancer. The odds ratio of CIN, adjusted for age and year of diagnosis, for anal vs colon cancer was 5.2 (95% confidence interval [CI] 3.3-8.3), that for anal vs stomach cancer 3.6 (2.1-6.0), and that for anal vs vulva cancer 1.6 (0.9-2.9). The median time from diagnosis of CIN to diagnosis of the registered cancer was 151 months for anal, 112 months for vulva, 114 months for colon, and 126 months for stomach cancer. The association with previous invasive cervical cancer was also investigated; no patient with cervical cancer in this second analysis had been included in the CIN analysis. The odds ratios were similar. In addition, anal cancer patients were significantly more likely to have had cervical cancer than were patients with vulva cancer (odds ratio 1.8 [1.0-3.9]). The strong association between anal cancer and CIN/invasive cervical cancer suggests that these cancers share common risk factors. The association is at least as strong as that between cervical and vulva cancer.

Adolescent

A review of cervical cancer and cervical screening: implications for nursing practice.

In this paper we review epidemiological and other research evidence on cervical cancer and cervical screening. We outline recent research evidence implicating sexually transmitted human papillomavirus as one of the causes of cervical cancer, but stress the uncertainty surrounding the causes and natural history of the disease. We go on to discuss evidence on risk factors associated with increased incidence of and mortality from cervical cancer, including age, sexual behaviour, smoking, socioeconomic status and prolonged use of oral contraceptives. Cervical screening has reduced mortality in some countries, and we outline the necessary features of a successful, effective screening programme before going on to describe why screening failed in Britain, at least until the late 1980s. Current screening policy is designed to remedy this, and we discuss its implications, and those of previous research, for nursing practice.

Female

Prevalence of human papillomavirus (HPV) infection in Basque Country women using slot-blot hybridization: a survey of women at low risk of developing cervical cancer.

Cervical smears from 1,178 women with cytologically normal cervices and 67 women with cervical intra-epithelial neoplasia (CIN) or cervical carcinoma were analyzed for the presence of HPV 6, 11, 16 and 18 DNA by slot-blot hybridization. HPV DNA was detected in 17% (95% CI: 14%-19%) of the women with a normal smear; 11% of infected women harboured HPV 16 and 18 (95% CI: 9%-13%, each). HPV DNA was detected in 54% (95% CI: 41%-66%) of patients with abnormal smear; the most prevalent virus type in this group was HPV 16 (45%; 95% CI: 32%-38%). In order to verify the slot-blot results, a proportion of the samples was also investigated by PCR. There was 88% correlation between the 2 tests. The high prevalence of HPV 16 and 18 infection demonstrated in our low-cervical-cancer-risk area further support the role of as yet unidentified co-factors as determinants of the different geographic rates of cervical-cancer incidence.

DNA, Viral

Cytological changes preceding cervical cancer.

Cervical smears were reviewed from 62 women who developed squamous carcinoma of the cervix up to 18 years later. The findings indicate that the prevention of cervical cancer by screening depends very largely on the detection of severe dyskaryosis. In this series there was no evidence that mild dyskaryosis was a forerunner of invasive disease. Cytology during the evolution of squamous carcinoma is not characterised by a dyskaryosis which progressively increases in severity. Instead the findings support new concepts that cervical cancer generally arises from an aggressive CIN 3 lesion widely present in the cervix, and in our series, established years before invasion occurs. It would be more useful to report cytology as showing either a low or high grade abnormality rather than distinguishing between different degrees of dyskaryosis.

Adult

[Detection of breast cancer and cervical cancer. Teaching life habits].

In the United States, annual deaths from breast cancer and cervical cancer outnumber deaths caused by all other types of gynecological cancer. Although early detection and intensive treatment can save the lives of a great number of victims, many Americans often fail to follow recommended detection procedures. The nurse practitioner's global approach and advanced level of knowledge allow her to intervene at all stages of care delivery, and consequently give her a key role in preventing these ailments. She is able to evaluate a client's state of health and the quality of health care offered to the clientele. She can explain to women the risk factors for cancer, design programs for early detection and intervention, and follow up on clients' treatments. By pointing out health care needs to the members of the care team, the nurse practitioner works toward improving care quality. She is called upon to defend women's interests in discussions likely to have an impact on the detection and treatment of breast cancer and cervical cancer.

Breast Neoplasms

Human papillomavirus and cervical cancer.

Cervical cancer is the fifth most common cancer worldwide, and is second only to breast cancer as the leading cause of cancer deaths in women. Half a million cases are diagnosed annually with the highest rates in developing countries.

Female