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International audience; Background: HPV vaginal self-sampling can be an alternative for women refusing cytological screening. Objectives: To describe HR-HPV types in 35-69 years old women from low socioeconomic groups not attending regular cytological screening in Marseille, France. Study design: A cervical screening campaign using HR-HPV self-sampling including 22,702 women aged 35-69 years living in low socioeconomic districts of Marseille was organized. A cytological and/or histological follow-up was undertaken for a subset of women harboring HR-HPV types. Abbott RealTime High Risk HPV test was used for screening, while INNO-LiPA HPV Genotyping Extra assay was used for genotyping. Results: 4245 self-samplings were performed (participation rate, 18.7%) out of which 609 (14.3%) were HR-HPV+ by the screening test including 114HPV 16 (18.7%), 41HPV 18 (6.7%), 454HR-HPVnon-16/18 (75.4%). A sample of 260 out of the 454HR-HPVnon-16/18 were genotyped by INNO-LiPA which revealed HPV52 (35%), 66 (22.6%), 51 (19.6%), 31 (15.7%), 39 (13%), 56 (10.4%), and 53, 35, 59, 33, 58, 82, 45, 68, 73 (= CIN2 lesions, (11 were HPV16+ and 8 were HR-HPVnon-16/18). Conclusion: This study illustrates the potential efficacy of self-sampling as a cancer screening strategy for socioeconomically deprived women who do not participate in regular Pap screening programs. (C) 2016 Elsevier B.V. All rights reserved.

The purpose of this study was to evaluate a conservative cold-knife section technique for treatment of cervical intraepithelial neoplasia (CIN). This procedure can be adapted to patient age, preservation of childbearing potential and extent of dysplasia.Prospective study.Gynecological Oncology Department in French Public Hospital.A total of 460 women treated for CIN between 1985 and 1999 were included.A conservative cold-knife cervical section followed by blanket suture reconstruction was used in all cases.Immediate operative results, recurrence and reproductive function were assessed.The mean length of the cervical specimen was 11.4 mm (range, 4-22 mm). Mean specimen thickness was strongly correlated with age: 10.6 +/- 4.1 mm in women40 years versus 12.1 in women40 years; p0.001. Complete excision was achieved in 395 cases (85.8%). Post-operative bleeding was observed in 5 cases (1.1%). The mean duration of follow-up was 62 months (range, 12.3-156.5 months). Recurrences developed in 26 patients (6.6%) including CIN 1 in 9 cases, CIN 2 in 9 and CIN 3 in 8. No patient developed carcinoma. The actuarial risk of recurrence was 2.4% (+/- S.D., 0.9) at 24 months and 7.8% (+/-S.D., 1.9) at 60 months. A total of 52 pregnancies were observed in 39 patients. No case of de novo infertility was reported post-operatively. Amenorrhea was noted in 1 patient (0.1%) and dysmenorrhea in 1 patient (0.1%).This conservative cold-knife section technique is effective for treatment of CIN with low morbidity and little adverse effect on childbearing potential. Exposure of the squamocolumnar junction (SCJ) greatly facilitates follow-up.

The relationship of age with prognostic factors and outcome of breast cancer has long been controversial due to numerous confounding factors. In order to clarify the prognostic value of age, we analyzed a homogeneous population of 1,266 patients treated for breast cancer at the same institution (mean follow-up: 62 months). Three groups were compared: patients under 35 years of age, non-menopausal patients over 35 years of age, and post-menopausal patients under the age of 70 years. A higher frequency of undifferentiated tumors, histoprognostic grade-3 cancer, microscopic lymph-node involvement and negative hormonal receptor status was observed in patients under 35 years. In addition, clinical but not anatomical tumor size was greater in young patients, suggesting higher stromal activity. Metastasis-free survival and overall survival were significantly poorer before 35 years. Differences were observed when patients were matched with regard to stage, anatomic size, histoprognostic grade, microscopic lymph-node involvement and receptor status. Multivariate analysis of both overall and metastasis-free survival demonstrated that age younger than 35 years was an independent risk factor. Younger women had a higher risk of local recurrence but, unlike older women, they did not experience any worsening of the already unfavorable outcome due to recurrence.

The distribution of PECAM-1/CD31 molecule was investigated in 133 breast carcinomas using monoclonal antibody and frozen sections. Anti-CD31 labels endothelial cells and reflects stromal angiogenesis. The CD31 immunoreactivity was evaluated by computer-assisted analysis of digitized microscopic images. The automatic screening of the whole preparation and the measurements of the mean CD31 immunostained surface was performed in each case. A similar procedure was achieved for p53, cathepsin D, P-gp, pHER-2/neu, Ki67, pS2 estrogen and progesterone antigenic sites immunodetection. The image analysis of positive CD31 surface was variable, ranging from 4% to 33% (mean 14.7%, SD = 5.43). The CD31 positive surface correlated (P < .01) with the Nottingham prognostic index, but not with the tumor size, the node status, the tumor grade, nor with the patient age. Also the CD31 immunoreactivity was independent of the pHER-2/neu, Ki67 antigen, p53, ER, PR and pS2 immunodetectable expression in tumors, but correlates with that of cathepsin D (P = .024) and P-gp (P = .028), which reflects the multi-drug resistance capacity of tumor cells. In conclusion, CD31 positive vessels assessed on frozen sections by image analysis constitute an excellent method of evaluating tumor stromal angiogenesis, and can be further used for clinical purposes. The results also suggest that the CD31/PECAM molecule may be involved in the spread of tumor by interacting with extracellular matrix lysis that results from the tumor cell proteasic activity and with multidrug resistance. (Key words : PECAM/CD31 ; Immunohistochemical assays ; Image analysis) Am J Clin Pathol 1995 ;103 :443-448.

The non-participation to cervical screening is the major determinant in the risk of mortality due to cervical cancer. In France, around 40% of women do not participate to regular screening. The cultural or economic barriers for performing screening by Pap test are numerous; one of the most frequent is the refusal of gynaecological examination. A persistent HPV(HR) infection is a necessary factor for developing cervical cancer. The HPV(HR) testing has a high sensibility to detect high grade cervical intra-epithelial neoplasia (CIN 2-3) and a satisfactory specificity after 30-35 years old. The principal objective of this study was to compare the participation rates in women 35-69 years old who did not perform a Pap test after a first individual invitation, either when an HPV(HR) auto-test was offered to be performed at home or a second invitation to Pap test was sent. We also evaluated the quality of the two tests, the positive results obtained by age groups and the following histological type of lesions diagnosed in the women with positive results. The study included 9,334 women, 35-69 years old, who did not realized a Pap-test during the 2 previous years and who did not respond at a first individual invitation. These non-responders were randomized into two groups: one group (n=4,934) received a second individual invitation and the other (n=4,400) an offer of receiving and performing an HPV auto-test at home. In women 35-69 years the participation to the second invitation to Pap test was significantly lower (7.2%) than the participation to auto-test (26.4%) with P0.001. The quality of the two tests was satisfactory; the auto-test was not altered by the postage to laboratory (non interpretable rate=1.4% [CI at 95%=0.65%; 2.15%]. From the 311 Pap tests done, 5.5% (17) were classified "abnormal" (nine ASCUS, one high grade and seven low grades). The follow up of 13 women out of 17 confirmed the diagnosis for 1 case of CIN2 and 2 cases of CIN3, 4 women are lost of follow up after 6 months. From the 939 HPV(HR) tests done, 6.2% (58) were positive. Such positivity rate was not influenced by age. Out of the 58 positive HPV(HR) cases, 27 only were of the 16 genotype (46.5% [CI 95%=33.7%; 59.3%]). This law rate is a consequence of an inversion of the ratio HPV 16 versus other types in women 60 years old and over. In this group, the follow-up of 36 women diagnosed five cases of CIN1, one of CIN2 and four of CIN3; 22 patients are lost of follow up at 6 months. Globally, in the studied population, an individual recall for pap test allowed to diagnose and treat 3 high grade lesions (7‰) and the dispatching of an auto test allowed the diagnosis and treatment of five high grade lesions (1,4‰), this difference is significant (P=0.02; OR=0.25 [0.05; 0.97]). The HPV(HR) auto-test seems to be better accepted than the Pap test in the 35-69 years old women previously non-responders to individual invitation, and the quality of the test is satisfactory. Such a test can be proposed to the 35-69 years old non-participant to Pap test to increase the coverage for cervical screening, if the rates of diagnostic examinations performed in case of an HPV(HR) positive is sufficiently high.

Immunocytochemical assays of cathepsin D were assessed in a series of breast carcinomas (n = 257) using monoclonal M1G8 anti-total cathepsin D and the avidin-biotin-peroxidase complex. Cathepsin immunoreactivity was compared in frozen and paraffin sections. All tumours were anti-cathepsin-positive. Positive staining was observed in carcinoma and stromal cells and in the extracellular matrix. The amount of immunodetectable cathepsin in tissue was measured by computer-assisted image analysis (SAMBA 2005). Both the percentage of immunostained tumour surface and the mean optical densities were processed as continuous variables for statistical analysis and correlated with prognostic factors. It was shown that cathepsin D was independent of the tumour size, the lymph node status, hormone receptors, and pHER-2/neu overexpression. Cathepsin was significantly correlated with anti-EGFR (P = 0.012) and Ki67 (P = 0.002) immunoreactivity, tumour grade (P = 0.032), vascular invasion (P = 0.0081), proliferation index (P = 0.0045), and, to a lesser extent with AgNORs (P = 0.0504) and the degree of hyperploidy (P = 0.057). Tissue fixation and paraffin embedding significantly decreased cathepsin immunoreactivity. These results show that cathepsin D is not a totally independent prognostic factor in breast carcinomas.

Immunocytochemical assays for EGFR were performed on frozen sections from breast carcinomas (n = 209). Results were evaluated by computer assisted image analysis to accurately define the percentage of immunostained surface and the mean optical densities. Thirty seven percent (n = 77/209) of the tumors were EGFR positive, but about one third of them were faintly reactive (35%). No significant relationship was observed between EGFR tumor content and patient age, tumor size, histological type, histoprognostic grade, or axillary lymph node status. A negative correlation was observed with the results of estrogen receptor immunocytochemical assays and a positive correlation with immunodetectable cathepsin D and Ki 67 antigen evaluated according the same method. No correlation was found with HER-2/neu protein, aneuploidy, nucleolar organizor region distribution, and nuclear morphometry, also assessed by image analysis. These results suggest that immunocytochemical assays assessed on frozen sections and evaluated by image analysis are suitable for current and standardized evaluation of EGFR which has been previously documented as a prognostic indicator in breast carcinomas.

Self-sampling using vaginal swabs could be a valuable alternative to screen for cervical cancer for women who do not attend regular cytological screening. The aim of this study was to determine the prevalence of high and low-risk HPV types and of HPV type 16 and 18 DNA load in self-collected vaginal swabs from 35- to 69-year-old Southern French women of low socioeconomic level or migrant populations who do not attend regular cervical screening. A good concordance (93.1%) was found between cervical brush and vaginal swabs in 29 samples. Self-collected vaginal swabs were examined from 120 women. HPV infection was found in 28 women (23.3%; median age 48 years), 17 (14.1%) of whom harbored high-risk HPV types. HPV type 16 was the high risk type found most frequently, followed by types 53, 31, 18, 58, and 66. The low-risk type detected most frequently was HPV type 6, followed by types 61, 70, and 81. The mean HPV 16 and 18 load was 6.3 log10 copies/106 cells and 2.4 log10 copies/106 cells, respectively. These results suggest that vaginal self-swabs can be a reliable tool for cervical cancer screening in non-attending and inadequately screened elderly women. J. Med. Virol. 82:1431–1437, 2010. © 2010 Wiley-Liss, Inc.

Individual cervical screening with pap-smears is the major cause of the decrease in incidence and mortality of cervical cancer in France since more than 30 years. But, for the last ten years, the decrease in mortality is limited due to the persistence of poor prognostic cases and the insufficiency of treatment efficacy in such patients. These cases are mostly observed in women who did not participate to regular screening. They are generally from low socioeconomic levels or migrant populations, or both. Such an observation leads us to organize 3 successive pilot campaigns (2001, 2003, 2005) in the Northern part of Marseille city where the rate of such poor population is high (37 to 45%). The women without a pap-smear indexed in the National Insurance Register for the last 3-2 years were invited by individual mailing to perform, free of charge, a pap-smear. The evaluation of each campaign helps us to improve the next one. The major changes from the 1st one to the 3rd one were to increase the number of free screening services, to send a second invitation to the non responders, and to organize local meetings with social workers and nurses to explain to the women the importance of performing regular screening tests. The final results after the 3 campaigns showed : out of the eligible women the participation rates are dramatically low evolving from 1,56 % to 2,48% and 6,87% of pap-smears done along the 3 campaigns ; the selection of women "without pap-smear" from the national Insurance register was not good, a great number of missing data was identified, explaining partly the extremely low rate of participation ; the factors increasing a little the participation are the second mailing of invitation (39 % of pap-smears realised) ; the total gratuitous of the screening (both sampling and reading) ; the oral information delivered locally by social workers and the proximity of the places to perform the test ; the quality of the pap-smears collected by gynecologists was good but insufficient for other health professionals, requiring a specific training for cervical cell collection. The organization of such pilot projects need to be followed to find better solutions to increase the participation to cervical screening of such populations who are at high risk of poor prognosis cervical cancers.

The aim of this study is to evaluate if the seriousness of invasive neoplasms of the uterin cervix actually observed is related to the apparition of rapid onset cases.219 invasive cancers of the cervix treated from 1988 to 1999 in a gynecological oncologic department.prognostic factors of cancers have been studied and compared to those of cases treated between 1975 and 1980 in the same department. The existence of cytological screenings has been searched and results have been analysed.Cervical cancers treated during the last 12 years have more serious prognostic factors than those treated during the former period. This evolution is shown by a progression of advanced stages of + 10.2%, an increase of lymph node invasion in proximal stages of + 13,4% and the doubling of number of adenocarcinomas. Though no change of the natural history of cancers has been proved. Only 42% of patients had profited of a cervical screening and cancers diagnosed at "stage I" are statistically more numerous in this group. Improvement should be brought up in the quality of samplings and of the care of abnormal results of cytological screening.

Hormone-replacement therapy (HRT) is widely used by post-menopausal women. Although this treatment may slightly increase the incidence of breast cancer, more and more cases are diagnosed while women are taking HRT. The purpose of this study was to ascertain the influence of HRT on prognostic factors and outcome of breast cancer. Data on all breast-cancer patients, including precise information on HRT, was prospectively and systematically recorded in a data base. From 1985 to 1995, 1379 post-menopausal women fulfilled the eligibility criteria for this study. All were treated by us (P.B. and L.P.) in our ward of a large public hospital of Marseilles, France. The clinical features, laboratory findings and survival rates in 142 HRT users who developed breast cancer while being treated were compared with those of 284 matched never user breast-cancer patients. Patients who developed breast cancer during HRT had fewer locally advanced cancers and smaller and better-differentiated cancers. Lymph-node involvement was significantly less frequent in the user group than in the non-user group (non-significant). Estradiol receptivity was both qualitatively and quantitatively lower in users. There was no significant difference with regard to recurrence and metastasis-free survival and overall survival. We conclude that HRT does not affect the prognosis of breast cancer. Regular surveillance during HRT allows early detection of smaller lesions. The higher number of well-differentiated cancers and the distribution of hormone receptivity may reflect interaction between neoplastic tissue and exogenous hormones.

To improve local and systemic control of bulky (>4 cm) and/or advanced primary cancer of the uterine cervix, 35 patients were treated with concomitant cisplatin (CDDP), 5-fluorouracil (5-FU) and split course hyperfractionated radiotherapy. Radiation was administered to the pelvis in five-day courses at a dose of 1.5 Gy twice daily every 21 days until a median dose of 45 Gy was reached. 15 Gy more were administered to involved parametrium or central tumor by external radiotherapy or brachytherapy. The irradiated zone was extended to include paraaortic lymph nodes if necessary. CDDP was administered at a dose of 20 mg m −2 and 5 FU at a dose of 500 mg m −2 from day one to day five of each course. The median number of combined treatment courses per patient was four (1–6). Local responses were obtained in 19 out of 24 patients in whom evaluation was feasible (i.e. who did not undergo surgery prior to combined therapy). Median survival was not attained with a median follow up of 33 months, three year overall survival was 62% and 52% in patients with local control and in the whole population respectively. Several patients with stage III and IV tumors achieved a very long survival. Acute toxicity was manageable but three patients required surgical repair of late radiation complications. This combined chemotherapy and radiotherapy resulted in good local control and did not rule out surgery.

A series of 222 tumor samples stored at –80 °C in the authors’ tumor library were investigated with anti- p53 (PA 1801) and streptavidin-biotin- peroxidase complex. The p53 immunoprecipitates were quantified by densitometry assessed by image analysis of digitized microscopic images. Two parameters, percentage of positive surface and mean optical densities, were compared with the patient’s outcome (follow-up = 96.8 months) (life table method, Mantel Cox test, BMDP statistical software). The p53 expression significantly correlated with a poor overall survival ( P = .0063), metastasis-free survival ( P = .024), and recurrence-free survival ( P = .022) at a 20% cutoff point of positive immunoreactive tumor surface. A strong prognostic significance was observed in the node-positive subset of patients but not in the nodenegative subset, except for recurrence-free survival ( P = .047). The results indicate the clinical relevance of p53 evaluated by quantitative immunocytochemistry.

In France, about 40% of women aged 25-65 years do not participate in regular screening and thus are at high risk (HR) of cervical cancer. Human papillomavirus (HPV) vaginal self-sampling is a valuable alternative in this population. This study aimed to assess the prevalence of HR and LR (low-risk) HPV infection in 3767 women aged >35 years from mid-socioeconomic backgrounds who carried out HPV vaginal self-sampling at home. HPV vaginal self-sampling was better accepted than the Pap-test in women aged 35-69 years who were previously non-responders to individual invitation. From the 933 self-collected swabs studied (24.7%), 62 were HPV-infected (6.6%), and 73 HPV types were found. HPV 16 was the most frequently found (43.5%), followed by 53 (23.2%), 18 (12.3%), 66 (12.3%), 31 (6.8%), 33 (5.4%) and 58 (2.7%). Ten women (16.2%) were infected by multiple HR-HPV types. Median HPV 16 load was 104.000 copies/10(6) cells and median HPV 18 load was 833 copies/10(6) cells. Six women (9.3%) harboured LR-HPV types. The 12-month follow-up of 43 HR-HPV positive women (69.3%) revealed CIN2-3 lesions in three women (6.9%), all HPV 16 infected, and harbouring an HPV 16 load >5 log(10) copies/10(6) cells. Women harbouring HR-HPV types other than HPV 16/18 were older than women harbouring HPV 16/18 types (55 years vs. 46.9 years, p 0.0008). The high frequency of HR-HPV types in women >50 years deserves further investigation to elucidate the mechanism involved (re-infection or reactivation).