Prevalence of cervical dysplasia and HPV infection according to sexual behavior.

A total of 165 uterine cervix smears from Venezuelan women were examined by cytological techniques to identify malignant and pre-malignant cervical changes, as well as to identify Human Papilloma Virus (HPV) DNA types 6, 11, 16, 18, 31, 33 and 35. Of these smears, 119 were from nonmonogamous women who participated in a cervical carcinoma screening program. In this group, HPV-DNA was detected by hybridization in 42 samples (35%) and cervical intraepithelial neoplasia (CIN) in 13 (11%). Forty-six monogamous aboriginal women were similarly studied and no evidence of abnormal cytology or HPV-DNA of the types studied here was found in any of them. In the non-monogamous group, age at first sexual intercourse and index of parity were not associated with cervical HPV infection and/or CIN. The rates of HPV infection, however, were significantly different between the two populations, confirming that sexual behavior involving multiple partners is associated with HPV infection.

In situ hybridization analysis of HPV DNA in cervical precancer and cervical cancers from China.

A series of 103 cervical biopsies derived from 103 women during July 1958 to September 1963 from Beijing, China were investigated with in situ hybridization for the presence of HPV6, 11, 16, 18, 31 and 33 DNA. The mean age of the patients was 46.1 + 10.6 years with a range of 24-74 years. Morphological features of HPV infection were found in 80 (77.7%) biopsies. Invasive cervical cancer was diagnosed in 43 biopsies and cervical intraepithelial neoplasia CIN I, CIN II and CIN III in 9, 9, and 27 cases, respectively. A total of 63.1% (65/103) of the lesions had morphological features of HPV infections associated with CIN or invasive carcinomas. Altogether, 31.1% (32/103) of the biopsies were shown to contain HPV DNA. Of the cases showing HPV morphology, 43.1% were HPV DNA positive. HPV16 (30/32) was the most frequent type, followed by HPV11 and 18, whereas no lesions with HPV6, 31 or 33 were found. A total of 19/43 (44.2%) of the invasive carcinomas contained HPV DNA. HPV DNA positivity and the grade of CIN showed a statistically significant correlation (P = 0.0011). Our study demonstrated the presence of HPV in cervical lesions among Chinese women in the late 1950's and early 1960's when a single sexual partner was the rule and also supports the concept that HPV has as an important etiological role in cervical cancer, the highest risk being associated with HPV type 16. The applicability of in situ hybridization in retrospective assessment is emphasized.

[Detection of HPV-DNA in the various uterocervical lesions by in situ hybridization].

We detected HPV (Human Papilloma Virus) -DNA in various uterocervical lesions by in situ hybridization using biotinylated DNA probes. In cases positive for HPV, the nuclei of the epithelial cells was purple to blackish purple. In 2 of 6 cases of chronic cervicitis, HPV-DNA was detected in the outer layer of the squamous epithelium. Eleven of 19 with mild dysplasia (57.9%) showed a positive reaction in the upper one-third of the epidermis in a mainly consisting of koilocytotic cells. All 6 patients with moderate dysplasia had positive cells among the koilocytotic cells and atypical cells in the middle layer. Five of 11 patients with severe dysplasia had scattered positive cells. Two of them had atypical condylomatoid lesions. Eight of 32 patients with squamous cell carcinoma were positive for HPV-DNA, but there was no consistent distribution pattern of the positive cells.

[Human papilloma virus (HPV) antigens and DNA in dysplasia and carcinoma of the uterine cervix].

Routinely paraffin-embedded sections of dysplasia, carcinoma in situ (CIS) and invasive (squamous) carcinoma of the cervix were studied to determine the participation of human papilloma virus (HPV) in these tissues. Morphological observation (1,059 cases) revealed condylomatous changes to reach 54% in dysplasia, 25% in CIS and 25% in invasive carcinoma. Condylomatous changes were also found to be 25 to 40% in the non-cancerous epithelia adjacent to in situ or invasive carcinomas. The immuno-peroxidase-PAP-method using anti-HPV serum was applied to 98 selected sections in which condylomatous changes were morphologically observed. HPV antigens were found to reach 56% in dysplasia, 42% in CIS and 35% in invasive carcinoma, and this result suggested that the morphologically observed condylomatous changes did not always coincide with virus maturation in the infected cells. By means of the in situ hybridization technique, HPV type-6, -11, -16 and -18 DNAs were all detected in dysplasia sections, whereas HPV type-16 DNA was demonstrated distinctively at a high rate among in situ and invasive carcinomas.

[Immunohistochemical studies on epidermal growth factor receptor in oncogenesis of uterine cervical cancer].

Recent studies have demonstrated that epidermal growth factor receptor (EGF-R) shows great homology with the v-erbB transforming protein and the amplified expression of EGF-R accompanies the malignant transformation of squamous epithelium of the uterine cervix. In this study, the tissue localization of EGF-R in the oncogenesis of uterine cervical cancer was examined by the avidin/biotin immunoperoxidase technique using anti-EGF-R monoclonal antibody. Normal squamous and columnar epithelium was almost negative for EGF-R. The positive rate of EGF-R increased in the precancerous lesions, whereas it decreased in invasive and metastatic cancer (mild dysplasia: 36%, moderate dysplasia: 57%, severe dysplasia: 77%, carcinoma in situ: 82%, microinvasive carcinoma: 80%, squamous cell carcinoma: 24%, glandular dysplasia: 67%, adenocarcinoma in situ: 75%, adenocarcinoma: 8%, adenosquamous carcinoma: 33%, metastatic carcinoma of the pelvic lymph node: 21%). The positive rate of dysplasia in follow up cases was high in the progressive group (regressive group: 0%, persistent group: 62%, progressive group: 80%). These results suggest that EGF-R may play an important role in the early stage of carcinogenesis of uterine cervical cancer, and it will be used as one of the markers in the prognosis of precancerous lesions of the uterine cervix.

Is it safe to prescribe hormonal contraception and replacement therapy to patients with premalignant and malignant uterine cervices?

The levels of estrogen and progesterone receptors in normal and abnormal uterine cervices were determined. The study group consisted of 14 patients with cervical intraepithelial neoplasia (CIN III) and 7 patients with invasive carcinoma of the cervix (stage IB-IIA). The control group included 23 patients who underwent total abdominal hysterectomy for menorrhagia, leiomyoma, etc. The concentration of total estrogen receptors in premalignant and malignant cervices did not differ from the patients with benign conditions of the cervix. The concentration of progesterone receptors was significantly higher in the nonaffected cervices than in the patients with preinvasive and invasive carcinoma of the cervix (P less than 0.05). We have shown that estrogen receptor concentrations do not differ between women with normal and abnormal uterine cervices. Therefore, we feel that the contraceptive pill is not contraindicated in women who have been treated for CIN III. We also maintain that hormone replacement therapy should be given, when indicated, to women who have been castrated following surgery and/or radiotherapy for invasive carcinoma of the cervix.

[In situ hybridization study on the localization of HPV DNA in the precancerous lesions of uterine cervix].

Human papillomavirus (HPV) types 16 and 18 have been found closely associated with cervical cancer. In order to investigate the relationship between HPV DNA and cervical precancerous lesions, we examined the formalin fixed specimens obtained from 22 cases of mild dysplasia, 33 cases of moderate dysplasia and 31 cases of severe dysplasia of the uterine cervix for the presence of HPV 6/11, 16 and 18 DNAs by in situ hybridization using the biotinylated HPV DNA probes. We also followed some HPV DNA positive cases of cervical dysplasia for more than 6 months prospectively. The results of in situ hybridization analysis revealed that HPV DNA was detected in the nuclei of koilocytosis, dysplastic cells and metaplastic cells. HPV 6/11 was positive in 27.3% (6/22) of mild dysplasia and 21.2% (7/33) of moderate dysplasia. On the other hand, HPV 16 positive rate increased with the grade of dysplasia and 36.4% (12/33) of moderate dysplasia, 61.3% (19/31) of severe dysplasia were positive for HPV 16 DNA. Some of the follow-up cases which were positive for HPV 16 DNA were later found to have carcinoma in situ. Our results suggest that HPV type 16 might play an important role in cervical carcinogenesis.

[Biometric research in the diagnosis of precancerous states and endocervical cancer]. / Biometricheskie issledovaniia v diagnostike predopukholevykh sostoianii i éndotservikal'nogo raka.

Smears of the endocervical channel taken from 58 patients with various endocervical conditions (reserve cell hyperplasia and dysplasia, reserve cell carcinoma in situ. Adenocarcinoma in situ, invasive glandular and poorly differentiated carcinoma) were stained by Feulgen method. Morphometrical (surface, perimeter, maximum and minimum diameter) and light microscopic (mean optical density of staining, its dispersion, DNA content) parameters of the epithelial cell nuclei were measured by means of telemetric image analyzer. The most informative biometrical indexes are found, the role of the DNA cytophotometry in the differential diagnosis is determined, the algorithm of the automated cytomorphological diagnosis of the dysplasia and endocervical carcinoma is developed.

A nuclear DNA study of uterine cervical dysplasia with reference to its prognostic significance.

To further define the nuclear DNA content of uterine cervical dysplasia and its relationship to prognosis and epidemiological features, a retrospective study using Papanicolaou stained cytological specimen and TICAS was undertaken. 1. Dysplasia patients was common among young females who had a background of low age first pregnancy, multiple Gravidity-Parity, the complication of inflammation and the use of hormonal contraceptives and progressed rapidly. It is recommended that a test should be repeated within 2 to 3 months regardless of the severity of the dysplasia and patients should be followed up for at least 2.5 to 3 years. 2. The DNA histograms were classified into 3 types (A,B and C): Type C, which had the stem line in an aneuploidy area, showed more severe dysplastic cases. This may be due to the proliferation rate and significant alternation in the chromosomes and mitoses. Nuclear DNA analysis using TICAS and Papanicolaou stained cytological material could discriminate between the progressive group and the persistent or regressive group. In addition, the mean nuclear area might be the best indicator of prognosis in uterine cervical dysplasia.