An epidemiologic study of cancer of the cervix, vagina, and vulva based on the Third National Cancer Survey in the United States.

Cases of invasive and in situ carcinoma of the lower female genital tract as reported in the Third National Cancer Survey in the United States were analyzed according to age, race, and geographic distribution. Results indicate that the incidence rates of in situ and invasive carcinoma of the cervix were greater in black than in white women, with a relative risk rate for black women of approximately two for both types of cervical carcinoma. For white women, the age-specific rates for invasive carcinoma of the cervix remained relatively constant after age 45, while for black women the age-specific rates for invasive carcinoma continued to increase after age 45. For both races, the patterns of age-specific incidence rates for in situ and invasive carcinoma of the cervix were not similar to those for carcinoma of the vagina or vulva. The pattern of age-specific incidence rates of adenocarcinoma of the cervix did not resemble those for in situ or invasive squamous cell carcinoma of the cervix. The rates for adenocarcinoma of the cervix demonstrated patterns similar to those for intraductal carcinoma of the breast. Results of the study are discussed in relationship to the field theory of carcinogenesis as developed for the lower female genital tract.     

Premalignant lesions of the uterine cervix in a large cohort of Israeli Jewish women

Israeli Jewish women are at low risk for cancer of the uterine cervix. In view of absent screening programs in Israel, there are only scarce data available with regard to results of PAP smears. The aim of this study was to assess the incidence of premalignant cervical lesions in the largest sample of PAP smears reported so far from Israel. We retrospectively analyzed the results of 297,849 PAP smears, which had been examined in a single laboratory, during 9 years (1991–1999). The incidence of low- and high-grade squamous intraepithelial was 0.69% and 0.29%, respectively. Our data indicate similar incidence rates for premalignant lesions in Jewish Israeli women as observed in Western countries, but no increase during the study period. In spite of relatively high incidence rates for premalignant lesions of the uterine cervix, the incidence rate for invasive cervical cancer remains conspicuously low. For unknown reason the conversion rate from premalignant cervical lesions to invasive cancer is lower in Israeli Jewish women than in European and North American women. We discuss possible reasons for this phenomenon and suggest that at this time mass screening for cervical cancer in Israel may probably not be justified.     

Survival data of Israeli Jewish patients with squamous cell carcinoma of the cervix treated by irradiation

During a 9-year period 61 Israeli Jewish Patients with histologically confirmed invasive squamous cell carcinoma of the uterine cervix (SUC) were treated by irradiation alone. A large proportion of the patients (44.2%) were more than 60 years old and only 27.9% were diagnosed as having stage IB disease. This is attributed to low awareness and infrequent cytologic screening. There is a trend for a large proportion of stage IB patients among those younger than 59 compared to those older than 60 years. The overall 5-year survival rate was 52.2% and the survival of patients with stage IB (72.6%) was significantly higher than in more advanced stages. In addition to clinical stage, age at diagnosis and method of irradiation also influenced survival rates.     

The presence of HPV 16, 18 and p53 immunohistochemical staining in tumor tissue of Israeli Jewish women with cervical and vulvar neoplasia

The incidence of cervical neoplasia in Israeli Jewish women is persistently lower, while that of vulvar carcinoma is comparable to that in other populations. The aim of the present investigation was to assess the prevalence of HPV and of immunohistochemically detected mutant p53 in Israeli Jewish women with cervical and vulvar neoplasia compared with other populations. Tissue sections from formalin-fixed paraffin-embedded blocks of ten patients with CIN III, 29 with invasive squamous cell carcinoma, three with adenocarcinoma and 14 with invasive vulvar carcinoma, were examined for the presence of HPV 16 and HPV 18 DNA by PCR amplification, and for mutant p53 protein by immunohistochemical staining. HPV negative cases were re-examined with a sensitive primer. HPV DNA was detected in eight patients with CIN III and in 23 patients with invasive squamous carcinoma. In the remaining cervical squamous neoplasia tissue analysis with the sensitive primer could not be done. HPV DNA was also detected in two patients with adenocarcinoma and in nine (64.2%) patients with vulvar carcinoma. Positive p53 immunohistochemical staining was found only in one CIN III patient, in six (20.7%) squamous carcinoma and in 11 (78.6%) vulvar carcinoma patients. Of the p53 immunohistochemical staining positive tissues, two with cervical carcinoma and six with vulvar carcinoma were also HPV-positive. The prevalence of HPV and of positive p53 immunohistochemical staining in our series of Israeli Jewish women with cervical and vulvar neoplasia is similar to that in other populations, suggesting that the etiological factors are probably also alike.     

A decreasing incidence of ovarian carcinoma in Israel

The aim of the present study was to assess the incidence trend of invasive epithelial ovarian carcinoma in Israel. We assessed the incidence rate of invasive epithelial ovarian cancer in Israeli Jewish women during the 10-year period from 1993 to 2002 based on data obtained from the population-based Israel National Cancer Registry. There was a gradual significant decrease in the incidence of ovarian cancer from 9.64 in 1993 to 6.55 in 2002. The decrease in incidence was evident in all ethnic groups except those born in Asia and in all the age groups older than 35 years. The decrease in incidence of ovarian carcinoma is gratifying, but its reason remains obscure.     

Comparison of adenocarcinoma and squamous cell carcinoma of the uterine cervix: a population-based epidemiologic study.

OBJECTIVE: Our objective was to compare epidemiologic and clinical characteristics of adenocarcinoma with those of squamous cell carcinoma of the cervix, with respect to risk by ethnic group, age at diagnosis, stage of disease at diagnosis, and survival. STUDY DESIGN: All data were obtained from the Cancer Surveillance Program of Orange County, California, from 1984 through 1989. A total of 152 cases of adenocarcinoma and 457 of squamous cell carcinoma of the uterine cervix were included. RESULTS: Adenocarcinoma of the cervix was diagnosed at a younger age and an earlier stage than squamous cell carcinoma. Hispanics have the highest risk for squamous cell carcinoma, whereas Asians have the highest risk for adenocarcinoma compared with whites. No differences were observed between the two histologic types in prognosis and survival. CONCLUSION: Differences between the two histologic types of cervix cancer were found in the age at diagnosis, the extent of disease, and the ethnic distribution. In spite of these differences, prognosis and survival were not affected by histologic type.     

Pregnancy-associated invasive squamous cell carcinoma of the vulva in a 28-year-old, HIV-negative woman. A case report

BACKGROUND: The incidence of invasive squamous cell carcinoma of the vulva in women under 40 years of age has been increasing, particularly in association with human papillomavirus. Invasive vulvar carcinoma is rare in women under 30, as is an association with pregnancy. We report on a 28-year-old woman who was diagnosed with invasive squamous cell carcinoma of the vulva during pregnancy. CASE: The patient, gravida 5, para 4105, HIV negative, presented to the emergency room with vulvar pain. She had delivered a term infant three months earlier at another institution and was diagnosed with squamous cell carcinoma of the vulva at that time. At this admission, a 4.0-cm, ulcerated lesion involving the left labium minus was noted. The patient underwent examination under anesthesia with bilateral inguinal lymph node dissection, cone biopsy, radical vulvectomy and excision of perianal lesions. CONCLUSION: This case demonstrates the need to biopsy all suspicious vulvar lesions, even in young and pregnant women.     

Incidence, mortality, and prognostic factors of small cell carcinoma of the cervix

OBJECTIVE: To compare the incidence, mortality, and presentation of small cell carcinoma of the cervix with other histologies. METHODS: From 1977 to 2003, 290 women with small cell carcinoma of the cervix uteri were identified from the Surveillance, Epidemiology, and End Results database. Also, 27,527 patients with squamous cell carcinoma of the cervix and 5,231 patients with adenocarcinoma of the cervix were identified for comparison. The annual incidence was calculated and examined for trend. Patient and disease characteristics were compared among histologies. Univariable analyses were conducted using the log-rank test. Multivariable analysis was performed using Cox regression. RESULTS: The mean annual incidence for small cell carcinoma was 0.06 per 100,000 women, compared with 6.6 and 1.2 for squamous cell carcinoma and adenocarcinoma, respectively. There were significant differences at presentation between small cell carcinoma compared with squamous cell carcinoma and adenocarcinoma for race, treatment, International Federation of Gynecology and Obstetrics stage, and lymph node involvement (P<.05). A trend for improved survival was identified for adenocarcinoma (P=.036) and squamous cell carcinoma (P<.001) but not for small cell carcinoma (P=.672). Five-year survival for small cell carcinoma (35.7%) was worse compared with squamous cell carcinoma (60.5%, hazard ratio 0.55; 95% confidence interval (CI) 0.43-0.69) and adenocarcinoma (69.7%, hazard ratio 0.48; 95% CI 0.37-0.61). On multivariable analysis, age, stage, and race were prognostic for survival in women with small cell carcinoma (P<.05). CONCLUSION: Small cell carcinoma is a rare histology of cervical cancer associated with a worse prognosis and a predilection for nodal and distant metastasis. The decrease in survival was marked in early-stage and node-negative patients. Because of the high rates of nodal involvement even with early-stage disease, multimodality treatment with radiotherapy and chemotherapy should be considered. LEVEL OF EVIDENCE: II.     

Cervical cancer in Canada: Changing patterns in incidence and mortality

Abstract. Liu S, Semenciw R, Probert A, Mao Y. Cervical cancer in Canada: Changing patterns in incidence and mortality.
Data on incidence of cervical cancer by histologic subtype and mortality for the Canadian provinces of Ontario, Saskatchewan, and British Columbia were used to examine time trends by age, calender period, and birth cohort. Age-adjusted incidence rate of squamous cell carcinoma of the cervix decreased from 11.1 per 100,000 women in 1970–72 to 5.3 in 1994–96, while the rate for cervical adenocarcinoma increased from 1.1 per 100,000 women to 1.5 over the same period. Age-adjusted mortality rate declined from 7.9 per 100,000 women in 1953–55 to 1.9 in 1995–97. The patterns in age-specific mortality rates in 1953–72 were different from those in 1973–97; younger women experienced larger reductions in mortality during the earlier period while older women benefited to a greater extent during the latter period. Age-period-cohort modeling showed that cohort effects were responsible for the decreasing trends in incidence of squamous cell carcinoma of the cervix and increasing trends in adenocarcinoma, and both period and cohort effects account for the observed trends in mortality. The results suggest that Pap smear screening has played a significant role in the reduction in squamous cell cervical carcinoma. The causes for the increase in cervical adenocarcinoma are unclear.     

Carcinoembryoinc antigen in cervical and vulvar cancer patients. Serum levels and disease progress.

Serial carcinoembryonic antigen (CEA) assays were performed on 10 patients with primary invasive squamous cell carcinoma of the cervix, 7 patients with recurrent squamous cell carcinoma of the cervix, and 5 patients with invasive squamous carcinoma of the vulva. Plasma CEA determinations were accomplished by radioimmunoassay, using a modification of Hanson's method. In 8 of the 10 patients with invasive squamous cell carcinoma of the cervix, positive CEA values dropped to normal ranges during the course of radiotherapy, usually in the first 4 weeks of treatment. A similar decrease in patients' serum values was seen after surgical extirpation of recurrent squamous cell carcinoma of the cervix by pelvic exenteration. Serum values also dropped to within normal limits in a limited number of patients with squamous cell carcinoma of the vulva after complete removal of all gross disease. Persistence of disease was associated with all gross disease. Persistence of disease was associated with chronically elevated values. A suggestion is made that patients with elevated CEA values may be followed with serial determinations to substantiate complete eradication of their disease.     

Epidemiological differences between adenocarcinoma and squamous cell carcinoma of the uterine cervix

Adenocarcinoma of the uterine cervix was significantly more common than squamous cell carcinoma of the cervix in unmarried patients (relative risk 2.07) and in nulliparous patients (relative risk 1.96). It also occurred more often in women with arterial hypertension (relative risk 3.62), previous subtotal hysterectomy (relative risk 3.89), and agrarian life style (relative risk 2.95). No difference was noted in mean age, age distribution, age at marriage, age at first delivery, menarche, or menopause. No association of adenocarcinoma of the cervix with pregnancy was found. On the basis of common risk factors it is suggested that cervical adenocarcinoma is epidemiologically more closely related to endometrial adenocarcinoma than to squamous cell carcinoma of the cervix.     

Study of sequences of DNA of the human papilloma virus genotypes 6 and 16 in patients with cancer of vulva and cervix uteri

Puntaction hybridization method was used to determine the incidence of the human papilloma virus infection in cases with the squamous cell cancer of the vulva and cervix uteri. The presence of sequences of DNA of the HPV genotype and 16 was found in 74.2% of cases, which points to a suspicion for the involvement of the above viruses in etiology of cervix uteri cancer, as well as vulva cancer.     

A cohort analysis of cervical cancer in Israeli Jewish women

The incidence of squamous cell cervical cancer was studied in Jewish Israeli women between 1961 and 1981. The 1052 cases and the 27,832,272 women-years of observation were divided according to continent-of-origin, year-of-birth, and immigration-wave cohorts. Age-adjusted odds ratios were calculated for each cohort and compared. The incidence of cervical cancer was shown to have changed according to cohort year of birth, most significantly in women born in Europe and America. The highest risk in this group was seen in women born in 1891-1895 and 1941-1945 and the lowest in women born between 1926 and 1935. A high risk was also observed in all cohorts of North African women. There was a sharp rise in risk for women of all origins born after 1940. Immigration to Israel at a younger age was correlated with reduced risk for cervical cancer. It has been shown that epidemics of sexually transmitted diseases (STDs) are followed in time by epidemics of cervical cancer. Since there was an epidemic of STDs in Israel between 1967 and 1970, our results also suggest that there is a rise in the risk for cervical cancer in women who were sexually active during the epidemic of STDs. Because of the low rates for cervical cancer traditionally observed in Israeli women, routine screening was not done in Israel in the past. Should the relative risk for cervical cancer in women exposed during the 1967-1970 epidemic continue to be high, screening may prove worthwhile.     

Pelvic exenteration, University of Michigan: 100 patients at 5 years

One hundred patients undergoing pelvic exenteration (total 69, anterior 13, posterior 18) at the University of Michigan Medical Center from 1964-1984 are reported. All patients were followed for at least 5 years or until time of death. The overall cumulative survival was 66% at 3 years and 61% at 5 years. The age of the patients ranged from 21-74 years (median 53). The type of pelvic neoplasm included squamous cell of the cervix, 57; adenocarcinoma of the cervix, nine; squamous cell carcinoma of the vulva, 12; squamous cell carcinoma of the vagina, eight; vaginal sarcoma, four; adenocarcinoma of the vagina, one; adenocarcinoma of the endometrium, four; uterine sarcoma, four; and adenocarcinoma of the ovary, one. The cumulative 5-year survival was significantly related to the presence of metastatic disease to the regional lymph nodes (8% 3-year and 0% 5-year survival), time interval from primary diagnosis to exenteration (within 1 year 44%, 1-10 years 60%, and over 10 years 95%), and cell type (squamous cell 68%, sarcoma 62%, and adenocarcinoma 26%). Patients with squamous cell carcinoma of the cervix (N = 57) had a cumulative 5-year survival of 73%, compared with nine patients with adenocarcinoma of the cervix, who had a 22% 5-year survival. No significant difference in survival existed for the type of exenteration, original stage of squamous cell cervical carcinoma, size of recurrent squamous cell lesion, or age of the patient. Early or late complications occurred in 49 patients. Two patients died in the postoperative period. Small-bowel obstruction was the most common complication seen in this series.     

Endocrine tumors of the uterine cervix: incidence,demographics, and survival with comparison to squamous cell carcinoma

OBJECTIVE: The aim was to describe the epidemiology of endocrine tumors of the cervix in comparison with invasive squamous cell carcinomas using population-based data reported to the Surveillance, Epidemiology and End-Results (SEER) program. METHODS: Retrospective analysis of actively followed cases reported to SEER from 1973 to 1998. Incidence, demographic characteristics, and survival were compared for endocrine and squamous tumors. RESULTS: There were 239 cases of endocrine tumors and 18,458 cases of invasive squamous cell carcinoma of the cervix included in the study. Mean age at diagnosis was 49 years for endocrine tumors versus 52 years for squamous cell carcinoma (P < 0.01). Endocrine tumors were more likely to present at a later FIGO stage (P < 0.01), and to have lymph node involvement at diagnosis (57 vs 18%, P < 0.01) compared to squamous cell carcinoma. Observed median survival for women with endocrine tumors was 22 months versus 10 years for women with squamous cell carcinoma. Age and FIGO stage-adjusted hazards of death were 1.84 times greater for endocrine tumors than for squamous cell carcinoma (95% CI 1.52-2.23). At all stages of disease, survival was worse for women with endocrine tumors compared to women with squamous cell carcinomas. CONCLUSIONS: Endocrine tumors of the cervix are extremely aggressive and survival is poor regardless of stage at diagnosis.     

Age-period-cohort analysis of cervical cancer incidence in Taiwan: differences between squamous cell carcinoma and adenocarcinoma

To examine the etiologic distinction between squamous cell carcinoma and adenocarcinoma of the cervix, the relationship between the incidence of both histotypes of cancer and age at diagnosis, time period at diagnosis and birth cohort was analyzed using data from the Taiwan Cancer Registry. Included in the study were all cases of both histotypes occurring during the period 1979–90 within a population of Taiwanese women aged 25 to 75 years. A log-linear model modified from the method of Osmond and Gardner was used for the analyses. Age-period-cohort analyses of age effect indicated that, prior to the age group of 49–51, there is an almost identical incidence of both histotypes with an approximate linear trend of age effect but that, after this time, there is a divergence, with the age effect of increase slightly declining with age for squamous cell carcinoma and clearly declining for adenocarcinoma. In regard to period and cohort effects, a substantial moderation of squamous cell carcinoma risk was exhibited with both advancing recent calendar periods and birth cohorts, while adenocarcinoma risk also has a moderation but to a lesser extent. The model also identified the changes in female sex hormones after the menopause as a determinant of the differing age effects, the efficiency of Pap smear screening practices as a determinant of the differing period effects, and changes in reproductive patterns as a determinant of the differing cohort effects. These findings may provide clues with which to develop etiologic hypotheses and support the contention of etiologic distinctions between both histologic types.     

Intraepithelial and Invasive Squamous Cell Neoplasia of the Vulva: Trends in Incidence,Recurrence, and Survival Rate in Norway

Objective: To characterize time trends in incidence of intraepithelial and invasive vulvar neoplasia, transition of intraepithelial vulvar neoplasia to invasive cancer, and survival rate based on a total population.Methods: The Cancer Registry of Norway was used to identify all Norwegian inhabitants diagnosed during 1956–1990 with squamous cell carcinoma of the vulva, and all those with intraepithelial vulvar neoplasia diagnosed during 1973–92.Results: The incidence rate of intraepithelial neoplasia increased three-fold from 1973–77 to 1988–92, and 3.4% changed into invasive disease. Multivariate analyses identified age as a significant variable. The age-adjusted incidence rate for squamous cell carcinoma was constant for the whole period. The ratio between recurrence and the total number of invasive cancer varied from 21% to 31%. The 5-year survival rates have not changed significantly over the period. Age was revealed as a strong prognostic factor, showing an excess death rate by increasing age.Conclusion: The incidence of vulvar intraepithelial neoplasia has increased substantially over the last 40 years, but that of invasive vulvar cancer has not changed appreciably.     

Cancer of the vulva and pregnancy: two cases and review of the literature

The cancer of vulva is predominantly a disease of postmenopausal women. But some cases have been reported in young women during pregnancy. Surgical management during pregnancy depends on several factors: gestational age at the diagnosis, lesion size, depth and location, lymph node status. We have conducted a national survey and report here the only two cases of squamous cell carcinoma diagnosed and treated during pregnancy at 26 and 15 weeks gestation. All vulva symptoms without signs of infectious should be examined with attention in order to detect vulvar lesions. When in doubt, a biopsy must be obtained. Management of vulva carcinoma is not modified during pregnancy, but the age of pregnancy must be considered.     

Primary Adenocarcinoma of the Uterine Cervix: Changing Clinical Profile

EDITORIAL COMMENT: The authors of this paper agreed to present their data concerning the changing incidence of primary adenocarcinoma of the cervix in an Indian centre as a summarized report. The interval of follow-up (6 moths) is short but the numbers of patients studied are large. There has been an increase in the number and percentage of cervical adenocarcinomas; in this series follow-up at 6 months suggests that prognosis is worse in women with adenocarcinoma compared to those with squamous cell carcinoma of the cervix.