Innovative uses of near-infrared spectroscopy in food processing.

Near-infrared spectroscopy (NIRS) has experienced widespread use as an analytical tool in the last 3 decades. Researchers today are exploring ways of applying NIRS that expand beyond compositional analyses into process control. Processes such as meat tenderness evaluation, curd cutting, and dough mixing have traditionally been controlled by highly skilled master craftsmen; new NIRS research applications are demonstrating that these complex processes can be monitored and controlled in situ to produce consistent, high quality end products with online NIRS technology. Additionally, researchers also now have the potential ability to develop new nondestructive spectroscopic techniques to probe the underlying molecular evolution of these products during processing.

High-risk human papillomavirus is sexually transmitted: evidence from a follow-up study of virgins starting sexual activity (intercourse).

Genital human papillomavirus (HPV) infection is generally considered to be sexually transmitted. However, nonsexual spread of the virus has also been suggested. The goal of this study was to assess: (a) the role of sexual intercourse in the transmission of HPV; (b) the determinants for seroconversion; and (c) the correlation between HPV DNA, abnormal cervical cytology, and serological response to HPV16. One hundred virgins and 105 monogamous women were randomly selected from a population-based cohort study in Copenhagen, Denmark, in which the women were examined twice with 2-year interval (interview, cervical swabs, Pap smear, blood samples). The presence of HPV DNA was determined by GP5+/6+ primers based HPV-PCR-EIA. HPV 16 virus-like particles (VLP) antibodies were detected by ELISA. All of the virgins were both HPV DNA negative and seronegative to VLP16, except for one woman who was weakly HPV 6 DNA positive. Only those virgins who initiated sexual activity became HPV DNA positive and/or VLP16 positive. The most important determinant of HPV DNA acquisition was the number of partners between the two examinations. The only significant risk factor for HPV 16 VLP seroconversion among women acquiring HPV DNA was HPV type. Our results show that sexual intercourse is important in the transmission of HPV, and that HPV 16 VLP seroconversion and the development of cervical lesions only occur after HPV transmission. Remarkably, no cervical lesions were found in HPV 16 DNA positive women who had seroconverted. Although based on small numbers, this may suggest that the development of antibodies had a protective effect.

Cervical cancer screening: knowledge of own screening status among women aged 20-29 years.

BACKGROUND: Studies have shown that accuracy of self-reported screening for cervical cancer is not optimal. In order to improve women's knowledge of their screening status and in broader terms improve communication between patient and doctor the risk groups who require special attention with regard to information have to be identified. The purpose of this study was to identify lifestyle and socio-demographic determinants for denying screening when in fact it had been performed. METHODS: A case-control study among 7,763 women aged 20-29 years from Copenhagen. Data were obtained by means of a personal interview using a standardized questionnaire and from a computerized pathology registry. Determinants for not knowing own screening status were identified using multiple logistic regression analysis. RESULTS: In all, 13% of the women could not state correctly that they had been screened for cervical cancer. The major determinant was younger age (adjusted odds ratio: 5.8, for women aged 20-22 years compared with women aged 26-29 years). Other determinants included few Pap smears, increasing years since last Pap smear, no previous abnormal Pap smear, lower education, never having used oral contraceptives, and current smoking. CONCLUSIONS: Knowledge about own screening status is not optimal in Denmark. Our study shows that doctors have to be extra careful with information to the youngest women and to certain other groups.

Different risk factor patterns for high-grade and low-grade intraepithelial lesions on the cervix among HPV-positive and HPV-negative young women.

Risk factors for cervical intraepithelial neoplasia have most often been studied in high-grade lesions. Furthermore, in a high proportion of the studies, human papillomavirus (HPV), the most significant risk determinant of cervical neoplasia, was not taken into account when evaluating other risk factors. To compare risk factors for ASCUS (atypical cells of undetermined significance), LSIL (low-grade squamous intraepithelial lesion) and HSIL (high-grade squamous intraepithelial lesion), we conducted a case-control study among 20 to 29 year-old women participating in a prospective cohort study in Copenhagen. It included 131 women with ASCUS, 120 women with LSIL, 79 women with HSIL and 1,000 randomly chosen, cytologically normal, control women. All participants had a personal interview and a gynecological examination including a Pap smear and cervical swabs for HPV DNA detection using general primer-mediated polymerase chain reaction. The most significant risk determinant of all 3 disease categories was the presence of genital HPV DNA. The risk factor pattern was nearly identical for ASCUS and LSIL, but differed significantly from that for HSIL. Stratified analysis by HPV-status showed that, apart from, respectively, smoking and parity among HPV-positive women, and smoking and number of sex partners among HPV-negative women, no additional risk factors were observed for ASCUS and LSIL. In contrast, among HPV-negative women with HSIL, long-term use of oral contraceptives was the most important risk factor. However, our result should be taken with great caution as it is based on very small numbers, and as it is unknown whether the HPV-negative lesions constitute a true entity. Among HPV-positive women, the risk of HSIL was associated with e.g., years of sex life without barrier contraceptive use, early age at first genital warts and smoking. Whether the risk factors that are applicable only to HSIL represent factors related to progression remains unknown.

History of genital warts in 10,838 women 20 to 29 years of age from the general population. Risk factors and association with Papanicolaou smear history.

BACKGROUND AND OBJECTIVES: The most important risk factor for cervical neoplasia is genital infection with certain types of human papillomavirus (HPV). Genital warts (GW) are an easily recognizable condition caused by HPV. Although only a fraction of HPV infections are clinical, a history of ever having had GW could serve as a marker for exposure to HPV. GOALS: To study the risk factors for ever having had GW. The association of GW with abnormal Papanicolaou (Pap) smear and relation to cervical neoplasia is also discussed. STUDY DESIGN: A case-control study among 10,838 women aged 20 to 29 years and reporting at least one lifetime sexual partner. The women were participants in a prospective cohort study on the relationship between HPV and cervical neoplasia in Copenhagen, Denmark. Data were obtained by means of personal interviews using structured questionnaires. RESULTS: In all, 1,820 women (17%) reported ever having had GW. The most important risk factor was the number of lifetime of sexual partners (adjusted odds ratio 5.2; 95% confidence interval: 3.4-8.0) for at least 40 partners vs. 1 to 2 partners). The number of regular partners, sexually active years, a history of chlamydial infection, and smoking were also associated with the risk of ever having had GW. Women who had had GW were 1.9 times more likely than other women to report an abnormal Pap smear. CONCLUSIONS: The study confirms the sexual transmission of the infection. There is also good concordance between risk factors for ever having had GW and cervical neoplasia. A close relationship between having had GW and an abnormal Pap smear was observed.

Determinants for genital human papillomavirus (HPV) infection in 1000 randomly chosen young Danish women with normal Pap smear: are there different risk profiles for oncogenic and nononcogenic HPV types?

Most studies of risk factors for human papillomavirus (HPV) DNA detection have focused on overall HPV positivity and have not examined determinants for high-risk and low-risk HPV types separately. We studied risk determinants for genital HPV infection in 1000 randomly chosen women (20-29 years) with normal cervical cytology from Copenhagen, Denmark. All women had a personal interview, a Pap smear, and cervical swabs for HPV DNA detection using a PCR technique. On the basis of their association with cervical cancer, the HPV types were categorized as belonging to a high-risk group ("oncogenic types") or a low-risk group ("nononcogenic types"). The overall HPV detection rate was 15.4%. Of HPV-positive women, 74% had oncogenic HPV types, and 30% had nononcogenic HPV types. Younger age and lifetime measures of sexual activity (notably, number of partners) were the main risk factors for the oncogenic HPV types. Furthermore, a previous Chlamydia infection was associated with the high-risk HPV types. In contrast, the most important determinants for nononcogenic HPV infection were contraceptive variables related to the physical protection of the cervix (condom or diaphragm) and number of partners in the last 4 or 12 months. Our study confirms the venereal nature of HPV infection. We hypothesize that the low-risk HPV infection, which correlates with recent sexual behavior, may be more transient than infection with the oncogenic HPV types, which correlates with lifetime exposure measurements of sexual habits.

Determinants for contraceptive use in young, single, Danish women from the general population.

Determinants for contraceptive use were studied in 5031, non-pregnant women aged 20-29 years from the general population in Denmark. Most women (72%) had never been pregnant, 34% had a history of a sexually transmitted disease, and 22% had ever had a legal abortion. Current contraception was most frequently condoms (60%) or oral contraceptives (33%). Among the women who used OCs or IUD, 32% reported additional condom use (double contraception). Important predictors of using one contraceptive method were lifetime number of sexual partners, parity, and age at first sexual intercourse for condoms and age for oral contraceptives. Also, women with a previous legal abortion were more likely to use condoms currently and women with a history of STDs were less likely to use condoms, but more likely to use OCs. Lifetime number of sexual partners was the only predictor of double contraception. Our data suggest a potential for reducing the number of unintended pregnancies and STDs in single women by increasing the information about the double principle in contraception.

PIP: The determinants of contraceptive use were investigated in a cohort study of 5031 sexually active, unmarried/non-cohabitating, non-pregnant women 20-29 years of age from Copenhagen, Denmark, identified through the Central Population Register. High proportions of these women reported a previous pregnancy (28%), abortion (22%), or sexually transmitted disease (STD) (34%). Current contraceptive use was reported by 4528 women (90%); the most frequently used methods were condoms (60%) and oral contraceptives (OCs) (33%). Among the 2066 women who used OCs or the IUD, 665 (32%) reported additional condom use (double contraception). Condom-only users were significantly more likely to have had first intercourse at age 17 or older, used condoms at first coitus, never have had an STD, and to have completed 11 or more years of education; also in this category were significant numbers of women with 15 or more life-time sexual partners and a prior legal abortion. Young age (20-23 years) was the most significant determinant of OC-only use. The only significant determinant of double contraceptive use was 15 or more life-time sex partners. The association between multiple sex partners and use of double contraception suggests that acquired immunodeficiency syndrome prevention messages are reaching the target population in Denmark.

[Patients with early stages of endometrial cancer should be spared adjuvant radiotherapy. Danish Endometrial Cancer Group]. / Patienter med tidlige stadier af endometriecancer bør skånes for adjuverende strålebehandling.

In an attempt to create uniform nationwide guidelines for the management of all stages of endometrial carcinoma, and to limit the use of adjuvant radiation therapy in stage I disease to high-risk patients only, a protocol was developed by the Danish Endometrial Cancer group (DEMCA). From September 1986 through August 1988, 1214 women in Denmark with newly diagnosed carcinoma of the endometrium have been treated according to this protocol. This figure represents all endometrial carcinomas diagnosed in Denmark during this two-year period. The primary treatment was total abdominal hysterectomy and bilateral salpingo-oophorectomy, no preoperative radiation therapy was delivered. In 1039 cases no macroscopic residual tumour and/or microscopic tumor tissue in the resection margins was found following surgery. Based on surgery and histopathology, these patients were classified as: P-stage I low risk (n = 641), P-stage I high risk (n = 235), P-stage II (n = 105) and P-stage III, Group 1 (n = 58). No postoperative radiation therapy was given to P-I low risk cases. P-I high risk, P-II, and P-III (Group 1) cases received external radiation therapy. Recurrence rate at 68-92 months follow-up was 45/641 (7%) in P-I low risk, 36/235 (15%) in P-I high risk, 30/105 (29%) in P-II, and 27/58 (47%) in P-III (Group 1) cases. Fifteen of 17 vaginal recurrences in P-I low risk cases were salvaged (mean observation time 61 months). In this population-based investigation it has been shown that P-stage low-risk patients are adequately treated by total abdominal hysterectomy and bilateral salpingo-oophorectomy, and that no pre- or postoperative radiation therapy is necessary.

Case-control study of risk factors for cervical squamous cell neoplasia in Denmark. IV: role of smoking habits.

The role of smoking and other risk factors for cervical neoplasia was investigated in a population-based case-control study of 586 women with histologically verified cervical squamous-cell carcinoma in situ (CIS), and 59 women with invasive squamous-cell cervical cancer from Copenhagen. Controls were randomly selected from the general female population using the computerized Danish Central Population Register. After adjustment for a variety of confounding variables, which were all significantly associated with CIS risk and included age, number of partners, proportion of sexually active life without barrier contraceptive use, years with intra-uterine devices, number of births, and age at first episode of genital warts (as a proxy measure for human papillomavirus exposure), current cigarette smoking was found to be significantly associated with CIS [adjusted relative risk (RR) = 2.4; 95% confidence interval (CI): 1.7-3.4]. Ex-smokers had a lower, but still significantly increased risk (RR = 1.6; 95% CI: 1.0-2.7). A dose-response relationship was present, especially for number of cigarettes smoked per day. In contrast, the crude estimates showed a weak association between invasive cervical cancer and smoking, which however disappeared after confounder control. The results of the present study support the hypothesis implicating smoking as a risk factor for CIS.

PIP: The role of smoking and other risk factors for cervical neoplasia was investigated in a population-based case-control study of 586 women with histologically verified cervical squamous-cell carcinoma in situ (CIS), and 59 women with invasive squamous-cell cervical cancer from Copenhagen. Controls were randomly selected from the general female population using the computerized Danish Central Population Register. After adjustment for a variety of confounding variables, which were all significantly associated with CIS risk and included age, number of partners, proportion of sexually active years without barrier contraceptive use, years with IUDs, number of births, and age at first episode of genital warts (as a proxy measure for human papillomavirus exposure), current cigarette smoking was found to be significantly associated with CIS [adjusted relative risk (RR) = 2.4; 95% confidence interval (CI): 1.7-3.4]. Ex-smokers had a lower, but still significantly increased risk (RR = 1.6; 95% CI: 1.0-2.7). A dose-response relationship was present, especially for number of cigarettes smoked per day. In contrast, the crude estimates showed a weak association between invasive cervical cancer and smoking, which however disappeared after confounder control. The results of the present study support the hypothesis implicating smoking as a risk factor for CIS.

Human papillomavirus--the most significant risk determinant of cervical intraepithelial neoplasia.

Sexual behavior has been consistently identified as a major risk factor for cervical cancer. Population-based studies have demonstrated that risk related to sexual activity is mediated by human papillomavirus (HPV) infection. We conducted a case-control study of 199 cases with low-grade squamous intraepithelial lesions or high-grade squamous intraepithelial lesions as defined by cytology and 1000 control women selected from an ongoing prospective cohort study in Copenhagen, Denmark. Furthermore, 131 women with equivocal smears (atypical squamous cells of undetermined significance) were examined as a separate borderline case group. At enrollment, all women had a personal interview and a gynecological examination including cervical swabs for HPV testing and a Pap smear. HPV testing was performed using a combination of general primer 5/6-mediated and type-specific polymerase-chain-reaction-based methods. Cervical HPV infection was by far the most significant risk factor for cervical squamous intraepithelial lesions. The relationship with HPV was observed for all grades, while strength of association was greater for more severe lesions. The importance of the previously identified epidemiological risk factors for cervical neoplasia was also demonstrated. However, most of the effect of these factors could be explained by taking HPV infection into account, except for schooling and smoking. Non-use of barrier contraceptives and smoking were the only significant risk factors in HPV-positive women. In HPV-negative women, a residual effect existed for different measures of sexual activity, and use of oral contraceptives and smoking constituted significant risk determinants Overall, 66% of cases could be attributed to HPV; however, if the results were restricted to histologically confirmed high-grade lesions, the proportion of cases that could be attributed to HPV infection increased to 80%.

Feasibility study of a randomised trial of ovarian cancer screening.

OBJECTIVES: To assess the feasibility of a randomised trial of ovarian cancer screening by vaginal ultrasonography. SETTING: A population based study, recruiting a random sample of the female population aged 46 to 65 years living in Copenhagen, Denmark. DESIGN: Randomised controlled trial allocating 50% to the study group having vaginal ultrasonography, and 50% to the control group having no examination. (a) Acceptability of the study was evaluated by the proportion of eligible women willing to participate in the study. (b) The false positive rate was evaluated as the proportion of women without ovarian cancer referred for an operation because of abnormal ovaries detected by ultrasonography. RESULTS: 950 (64.3%) of the 1477 eligible women participated in the study. At the first scan abnormal ovaries were detected in 54 of 435 women (12%), significantly more frequently among younger women. Nine women were referred for an operation because of abnormal findings in the ovaries, giving a false positive rate of 2%. Ovarian size and morphology found at operation corresponded with those at ultrasonography; none of them was malignant. CONCLUSIONS: A randomised controlled trial of ovarian cancer screening using vaginal ultrasonography seems acceptable in the general population. The rate of abnormal ovaries at ultrasonography with the cut offs used in this study was quite high. Such a study is, therefore, feasible, but it is proposed that it is carried out in an older age group (50-64 years) and that the cut offs used for ovarian size and morphology are re-evaluated. Second line tests, such as colour Doppler flow, should be considered in order to reduce the false positive rate.

[Increased risk of preterm delivery in women with earlier conization]. / Oget risiko for praeterm fødsel hos koniserede kvinder.

The object of the study was to determine the relation between cervical conization and preterm birth. All Danish women with singleton pregnancies who gave birth to their first infant in 1982 and second infant in 1982-1987 were included in a register-based cohort study. Information on pregnancy outcome and cervical conization in 1977-1987 was obtained from the Medical Birth Register and the National Register of Hospital Discharges. It was found that in a cohort of 14.233 women, 170 had had cervical conization. Thirty-four had had cervical conization before the first delivery, 62 between the first and the second, and 74 after the second delivery. Women with cervical conization had a significantly higher risk of preterm birth. Also, women with subsequent cervical conization had a higher risk of preterm birth in previous pregnancies. However, the risk of preterm birth was higher in women with previous than with subsequent cervical conization. It is concluded that cervical conization is correlated with preterm birth. Since women with subsequent cervical conization are at increased risk of preterm birth in preceding pregnancies, other factors than the surgical intervention may contribute to the significantly increased risk of preterm birth.

Detection of human papillomavirus (HPV) DNA in cervical swabs by the polymerase chain reaction: an evaluation of the sensitivity of the method in patients with HPV 16-harboring cervical lesions.

The polymerase chain reaction (PCR) was used to detect human papillomavirus (HPV) type 16 DNA in cervical swabs from 37 patients with HPV 16-harboring cervical lesions (15 carcinomas and 22 cervical intraepithelial neoplasias). Primers amplifying a sequence of the human beta-globin genome were used for internal control together with the HPV 16-specific primers. The cell samples were prepared for PCR analysis by two different methods: either by phenol/chloroform extraction or by boiling in the presence of a chelating agent. HPV 16 DNA was found in 27 swabs. The detection rates were identical with both methods of preparation. Four of the 10 false-negative swabs contained too little DNA to permit amplification with the genomic primers. Excluding these insufficient samples, the detection rate was 82%. Reasons for false-negative results may include low cell numbers or failure to obtain cells representative of the underlying lesion. In conclusion, the PCR offers a satisfactory method of HPV detection in cervical swabs. Cell preparation can be restricted to simple boiling with a chelating agent. For optimal results, samples containing less than 2 x 10(4) cells should be discarded, and genomic primers should be used for internal control.

Vulvar squamous cell carcinoma and papillomaviruses: indications for two different etiologies.

The vulvectomy specimens of 78 patients with vulvar squamous cell carcinoma were reviewed and examined for human papillomavirus (HPV) types 6, 11, 16, 18, and 33 by the polymerase chain reaction technique. The tumors were classified as keratinizing squamous cell carcinoma (KSC), as warty carcinoma (WC), and as basaloid carcinoma (BC). DNA of HPV types 16 and 33 was found in 2/51 KSC, in 12/17 WC, and in 10/10 BC. HPV types 6, 11, and 18 were not detected. Patients with WC and BC were younger, and 78% had VIN III lesions adjacent to the carcinoma. Patients with KSC were older and had a high incidence of dystrophic lesions, including lichen sclerosus, adjacent to the tumor. None of the KSC showed adjacent VIN III. In conclusion, vulvar carcinoma segregates into two categories, of which KSC seems to be the classic type, only rarely associated with HPV infection, and mostly affecting older women; WC and BC constitute an HPV-related subgroup of tumors occurring in younger patients and are associated with VIN III lesions from which they may emerge.

The value of CA 125 measurement before second-look laparotomy in patients with ovarian carcinoma.

Serum CA 125 levels were evaluated in 71 patients undergoing second-look laparotomy for primary epithelial ovarian cancer. With a cut-off limit of 35 U/ml, 17 of 45 patients with residual disease (38%) were CA 125-positive. All of 26 patients with pathological complete response were marker-negative. Second-look laparotomy may be avoided in a select group of patients with elevated CA 125 values.