Comparison of risk patterns in carcinoma and melanoma of the skin in men: a multi-centre case-case-control study.

We directly compared risk factors between 214 histologically confirmed melanomas (CMM), 215 basal-cell carcinomas (BCC) and 139 squamous-cell carcinomas (SCC) in a multiple case-case-control study with 349 controls from patients without dermatological disease admitted to the same hospitals. Subjects with fair hair had a significant risk increase for all types of tumours at a comparable level (OR(adj) for blonde hair: CMM 2.3; SCC 2.4; BCC 2.3). The effect of pale eyes was significant and similar for CMM and BCC (OR(adj) 2.6). Intermittent sun exposure measured in hours spent at beach during holidays was significant for both CMM (OR(adj) 2.6 for more than 7000 lifelong hours) and BCC (OR(adj) 2.1 for more than 7000 lifelong hours), while SCC exhibited a significant risk increase for chronic exposure to sunlight measured in hours of outdoor work (OR(adj) 2.2 for more than 6000 lifelong hours). In the case-case comparison using a multinomial logistic regression model, we found a statistically significant risk difference for pale eyes, and number of naevi in the CMM group, compared to other skin cancers. For intermittent sun exposure, there was a significant risk difference of BCC when compared to the risk of SCC. Factors influencing risk of SCC are different, with chronic exposure to sun playing a major role in causing this type of carcinoma.

Uveal and conjunctival malignant melanoma in Denmark, 1943-97: incidence and validation study.

PURPOSE: To study the incidence of malignant melanoma in the ocular region in Denmark during the period 1943-97. METHODS: The patients were mainly identified through the Danish Cancer Registry. Age-period-cohort modelling of the incidence rates was done based on age at diagnosis, calendar period and birth cohort in 5-year groups and for each gender. RESULTS: The age-standardized incidence of malignant melanoma in the ocular region was 0.78 for men (N = 1327) and 0.65 for women (N = 1242) per 100,000 person-years. Calendar period and birth cohort had no effect on the incidence in the ocular region or in the topography subgroups choroid/ciliary body and conjunctiva. However, the incidence increased with birth cohort for iris melanomas. CONCLUSIONS: The incidence of malignant melanoma in the ocular region was stable in contrast to a major increase in cutaneous melanoma in Denmark during the period 1943-97. The incidence of iris melanomas increased substantially, whereas the rate was stable for choroid/ciliary body and conjunctival melanomas.

Risk factors for genital HPV DNA in men resemble those found in women: a study of male attendees at a Danish STD clinic.

OBJECTIVES: Genital infection with certain types of human papillomavirus (HPV) is the most important risk factor for cervical cancer. The male sexual partner is supposed to be the vector of the infection. However, the knowledge of risk factors for genital HPV DNA in men is limited. The objective of this paper is to study the risk factors for HPV infection in men and to compare them with those found in women, including the study of whether there are different risk profiles for oncogenic and non-oncogenic HPV types. METHODS: From a sexually transmitted diseases (STD) clinic in Denmark, 216 men were consecutively included. A personal interview was done and material for genital HPV DNA detection was obtained with swabs. HPV DNA was detected by polymerase chain reaction (PCR). Odds ratios (OR) for HPV as well as for oncogenic and non-oncogenic types separately were computed with a 95% confidence interval (CI) by means of unconditional multiple logistic regresssion. RESULTS: The most important predictors of any HPV were lifetime number of sex partners (OR = 4.3; 95% CI 1.4 to 13.1 for 25-39 v 1-9 partners), young age, and being uncircumcised. The most important risk factor for oncogenic HPV types was lifetime number of partners, whereas number of partners in the past year and ever having genital warts were risk factors for the non-oncogenic HPV types. Young age predicted risk of both oncogenic and non-oncogenic HPV types. CONCLUSIONS: Most risk factors for HPV DNA detection in men resemble those found in women. As in women, the risk factor profile for the oncogenic HPV types was different from that of the non-oncogenic HPV types.

A pooled analysis of 10 case-control studies of melanoma and oral contraceptive use.

Data regarding the effects of oral contraceptive use on women's risk of melanoma have been difficult to resolve. We undertook a pooled analysis of all case-control studies of melanoma in women completed as of July 1994 for which electronic data were available on oral contraceptive use along with other melanoma risk factors such as hair colour, sun sensitivity, family history of melanoma and sun exposure. Using the original data from each investigation (a total of 2391 cases and 3199 controls), we combined the study-specific odds ratios and standard errors to obtain a pooled estimate that incorporates inter-study heterogeneity. Overall, we observed no excess risk associated with oral contraceptive use for 1 year or longer compared to never use or use for less than 1 year (pooled odds ratio (pOR)=0.86; 95% CI=0.74-1.01), and there was no evidence of heterogeneity between studies. We found no relation between melanoma incidence and duration of oral contraceptive use, age began, year of use, years since first use or last use, or specifically current oral contraceptive use. In aggregate, our findings do not suggest a major role of oral contraceptive use on women's risk of melanoma.

Development of an integrated method of skin phenotype measurement using the melanins.

Different types of melanin pigments have recently been identified and recognized as critical determinants of the photosensitivity of individuals. Eumelanin, the black to brown melanin pigments, are believed to protect against ultraviolet-induced cell damage, while phaeomelanin, the reddish brown variant, is thought to be photosensitizing. The relative, qualitative and absolute amount of melanin production under stimulation of solar radiation is likely to be genetically determined. The hypothesis of this study is that determination of these values can help in identifying those people who are less protected. However, these techniques must be evaluated at a population level and against traditional epidemiological measures. We assessed the amount and type of melanin in 195 subjects in four centres across Europe, relating the results to epidemiological measures such as skin characteristics, history of sunburns and number of naevi. The most important finding was that eumelanin and phaeomelanin have very different distributions in the population, being associated with other phenotype characteristics with different patterns. The relationship between phaeomelanin and eumelanin is linearly inverse in the range from black to dark blonde hair colour, while it is weakly directly proportional in the range from dark blonde to light blonde, with people with red hair showing a peculiar pattern. Phaeomelanin rather than eumelanin seemed to be independent of other skin characteristics. The results show the feasibility of a further study with an appropriate case-control design and accurate determination of melanin.

Teaching non-specialist health care professionals how to identify the atypical mole syndrome phenotype: a multinational study.

The atypical mole syndrome (AMS) phenotype is the strongest known risk factor for cutaneous melanoma but recognition of the phenotype has been claimed to be problematic and to require specialist assessment. This study determined the ability of previously unskilled doctors and nurses in five countries to recognize the phenotype after brief training. The system used was the AMS scoring system. This incorporates melanocytic naevus counts, clinical atypia of naevi and distribution of naevi. The agreement in scoring between the dermatologist and trained personnel was determined in 986 patients; overall agreement in diagnosis was 94.5% (kappa 0.70, P < 0.0001). The kappa scores in different countries ranged from 0.65 to 0.77 for individual naevus characteristics, indicative of good agreement. Accurate diagnosis of the atypical mole syndrome phenotype is possible by non-specialists. This has implications for collaborative studies of naevi, for screening and for both primary and secondary prevention of melanoma.

[Investigation of malignant melanoma in an "open house" setting]. / Undersøgelse for malignt melanom ved et "åbent hus"-arrangement.

Individuals with a self-evaluated risk of malignant melanoma were invited to an "open house" where trained dermatologists examined suspected lesions. The attendants filled in a short questionnaire relating to skin cancer risk factors. Persons with skin changes suspected for malignancy were referred for excision in the dermatological department. The clinical evaluation included dermatoscopy. Nine hundred and eleven individuals attended. Among 16 individuals referred for excision one malignant melanoma, one lentigo maligna melanoma and two in situ melanomas were histologically verified. Furthermore, 21 basal cell carcinomas were identified clinically. The most frequent clinical diagnoses were melanocytic naevi and seborrhoic keratoses.

Risk factors for HPV infection in women from sexually transmitted disease clinics: comparison between two areas with different cervical cancer incidence.

We have compared risk factors for human papillomavirus (HPV) infection in very sexually active women [attenders of clinics for sexually transmitted diseases (STDs)] living in 2 areas with a 4-fold difference in cervical cancer incidence, i.e., Greenland and Denmark. The results were compared with findings of HPV infection in men attending the STD clinics during the same period. Overall, 204 Greenlandic women (GW), 187 Danish women (DW), 103 Greenlandic men and 216 Danish men were included. A similar age distribution was found in the 2 female populations. The GW reported significantly more sexual partners, earlier first intercourse and more STDs, but HPV was less frequently detected in the GW (25%) than in the DW (35%). However, this could be explained by a difference in the age pattern of HPV prevalence seen in the 2 areas. In each geographical area, the age pattern of HPV prevalence in men was very similar to that seen in women. The most important risk factors for HPV detection were the same in both female populations, i.e., age, years since first sexual intercourse and number of partners in the last years. In conclusion, the pattern of risk factors for HPV infection was the same in STD women from a high-risk area and a low-risk area for cervical cancer. Our results also show that the use of an overall HPV prevalence for comparing populations is meaningless, even in populations with similar age distribution.

Detection of serum interferon-alpha by dissociation-enhanced lanthanide fluoroimmunoassay. Studies of patients with acute viral and bacterial infections.

A sensitive dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA) was evaluated for ability to detect interferon-alpha (IFN-alpha) in serum of patients with acute infectious disease of less than one week's duration and a fever of > 38 degrees C. None of 36 patients with confirmed or probable bacterial disease was IFN-alpha positive. In contrast, 13/26 patients with viral infections had detectable levels of IFN-alpha in serum, all clearly positive (> or = 10 U/ml). The IFN-alpha positive serum samples were obtained early after onset of clinical disease, after a mean of 2.4 days. The IFN-alpha positive samples were obtained from 10 of the 12 patients with influenza or flu-like infection, and 3 of the 5 patients with varicella or herpes zoster. The IFN-alpha negative patients with viral disease (n = 9) included five patients with mononucleosis. The DELFIA should be useful in further studies of the value of IFN-alpha determinations in the identification of acute viral infections.

What do Danes know about naevi, skin cancer and melanoma? Experience from a dermatological out-patient clinic.

A survey of public knowledge about naevi, melanoma/ skin cancer and sunscreens was undertaken in Denmark at a time when no public awareness campaign had taken place. A total of 339 study subjects, aged 18-79 years, was recruited at our dermatology outpatient clinic, and data were collected by a self-administered questionnaire. The study group differed from the population in that females and the younger age groups were over-represented. A knowledge score was calculated. Males, the oldest age group and those with shortest school education were less knowledgeable. The study revealed several points of public uncertainty and ignorance with regard to early signs of melanoma and risk factors, which need to be emphasized in future public education.

Avoidable cancers in the Nordic countries. Radiation.

Exposure to solar and ionizing radiation increases the risk for cancer in humans. Some 5% of solar radiation is within the ultraviolet spectrum and may cause both malignant melanoma and non-melanocytic skin cancer; the latter is regarded as a benign disease and is accordingly not included in our estimation of avoidable cancers. Under the assumption that the rate of occurrence of malignant melanoma of the buttocks of both men and women and of the scalp of women would apply to all parts of the body in people completely unexposed to solar radiation, it was estimated that approximately 95% of all malignant melanomas arising in the Nordic populations around the year 2000 will be due to exposure to natural ultraviolet radiation, equivalent to an annual number of about 4700 cases, with 2100 in men and 2600 in women, or some 4% of all cancers notified. Exposure to ionizing radiation in the Nordic countries occurs at an average effective dose per capita per year of about 3 mSv (Iceland, 1.1 mSv) from natural sources, and about 1 mSv from man-made sources. While the natural sources are primarily radon in indoor air, natural radionuclides in food, cosmic radiation and gamma radiation from soil and building materials, the man-made sources are dominated by the diagnostic and therapeutic use of ionizing radiation. On the basis of measured levels of radon in Nordic dwellings and associated risk estimates for lung cancer derived from well-conducted epidemiological studies, we estimated that about 180 cases of lung cancer (1% of all lung cancer cases) per year could be avoided in the Nordic countries around the year 2000 if indoor exposure to radon were eliminated, and that an additional 720 cases (6%) could be avoided annually if either radon or tobacco smoking were eliminated. Similarly, it was estimated that the exposure of the Nordic populations to natural sources of ionizing radiation other than radon and to medical sources will each give rise to an annual total of 2120 cancers at various sites. For all types of ionizing radiation, the annual total will be 4420 cancer cases, or 3.9% of all cancers arising in the Nordic populations, with 3.4% in men and 4.4% in women.

What do children aged 5 to 11 years old know about the sun and skin cancer? The practical difficulties of international collaborative research when analysis of language is involved.

The objective of this study was to determine the perceptions of primary school children about sun exposure and skin cancer, and the language they use about these issues, as a basis for the design of health promotional materials. In all, 2857 children in five European countries took part in the study and were compared with 641 Australian children participating in a similar study, since the latter have been exposed to more intensive health education about the sun. The 'draw and write' technique was used. In Europe the level of awareness about the risks of excessive sun exposure and the need to protect the skin was considerably lower than in Australia, although there was some variation within northern Europe. Amongst the European children acknowledging a need to protect the skin, the principal means of protection quoted was the use of suncreams, with inadequate awareness of the value of clothing, hats and shade. European children expressed greater approval of suntans than did the Australian children. Some methodological problems were encountered as a result of nuances in the languages involved, emphasizing difficulties in international research of this type.

Anal and cervical abnormality in women--prediction by human papillomavirus tests.

A total of 151 women at risk of human immunodeficiency virus infection were investigated, to study the strength of the association between cervix and anus regarding the presence of HPV and cytological abnormality. An equal percentage of women had abnormal cervical (12.2%) and anal (12.1%) Papanicolaou smears. HPV measured by PCR was detected in 93.3% of cervical squamous intraepithelial lesions (SIL) compared to 49.1% of normal cervical cytologies, and in 100% of anal SIL and 67.4% of normal anal cytologies, respectively. After controlling for HPV-PCR status, immunodeficiency, as measured by a low CD4+ count and HIV positivity, increased the detection of cervical and to some extent anal squamous intraepithelial lesions (SIL). We evaluated how precisely an HPV test could predict cervical disease and found that the HPV-PCR test was slightly more sensitive than the HPV-hybrid capture (HC) test (PCR: 93.3% vs. HC: 88.9%), whereas the HC test was significantly more specific (83.6% vs. 50.9%), and with a much higher positive predictive value (43.2% vs. 20.6%). Similar results were obtained for anal SIL. HIV positivity increased sensitivity, lowered specificity and increased the positive predictive value of the tests. A diagnosis of cervical SIL was associated with a more than 3-fold increased risk of a simultaneous abnormal anal smear (p < 0.05). In conclusion, cervical and anal disease were significantly associated and almost exclusively seen in the presence of HPV. Immunodeficiency and HIV positivity increased the risk of disease in HPV-positive subjects. Hybrid capture, which requires a higher viral load than PCR to detect HPV, was clearly superior in predicting cervical and anal disease. Altogether, these findings suggest that a high level of HPV infection may be important for the development of SIL in the population studied.

Risk of cutaneous melanoma associated with a family history of the disease. The International Melanoma Analysis Group (IMAGE).

In a combined analysis of 2952 melanoma patients and 3618 controls from 8 case-control studies in white populations the risk of cutaneous melanoma was 2.24-fold higher (95% CI, 1.76-2.86) in subjects who reported at least one affected first-degree relative than in subjects who did not. There was no evidence for heterogeneity in the relative risk between the studies, which were from a wide range of latitudes and hence degrees of sun exposure. The effect of family history on melanoma risk was independent of age, naevus count, hair and eye colour, and freckling. There was no evidence for a relationship between family history and primary site of melanoma but there was some suggestion that the familial patients were more likely to have superficial spreading melanoma or lentigo maligna melanoma than acral lentiginous melanoma or nodular melanoma.

Azithromycin levels in cervical mucus and plasma after a single 1.0g oral dose for chlamydial cervicitis.

OBJECTIVE: To determine the kinetics of azithromycin in cervical mucus and plasma. SUBJECTS AND METHODS: Azithromycin concentrations were determined in plasma and mucus samples from 20 women with cervical chlamydial infection one, seven and fourteen days after a single oral 1.0 g dose. RESULTS: In mucus, all measurable azithromycin concentrations were above the minimal inhibitory concentration against Chlamydia trachomatis on day 7 as well as on day 14. CONCLUSION: The high cervical mucus concentrations of azithromycin can explain the high clinical and microbiological efficacy.

[Dermatoscopy. An investigative method for the diagnosis of pigmented skin tumors]. / Dermatoskopi. En undersøgelsesmetode til diagnosticering af pigmenterede hudtumorer.

Dermatoscopy is a non-invasive investigative technique which makes it possible to evaluate the pigmented structures of the epidermis, the dermo-epidermal junction and the papillary dermal layer. The melanin pigmentation of the epidermal basal cell layers, the so-called pigment network is the primary target of dermatoscopy. A number of diagnostic criteria and variables for the dermatoscopy of pigmented skin lesions have been developed. Cutaneous malignant melanoma is still increasing in incidence and mortality. An early diagnosis is decisive for the prognosis. Therefore, it is urgent to develop practical investigative methods which can increase the diagnostic sensitivity. Dermatoscopy is such a method, but it demands training and experience. Lack of suspicious findings by dermatoscopy does not exclude malignancy. A safe diagnosis can only be obtained by a histological examination.

[Asymptomatic sexually transmitted infections among HIV-tested persons]. / Asymptomatiske seksuelt overførte infektioner hos HIV-testede.

We have prospectively determined the frequency of asymptomatic sexually transmitted diseases (STD) among patients seeking an HIV-test. In 246 patients, we observed 32 cases (13%) of asymptomatic STD, predominantly infections caused by Chlamydia trachomatis or human Papillomavirus. STD screening is of significance among patients seeking an HIV-test.

[Malignant lentigo]. / Lentigo maligna.

Lentigo maligna (LM) is a premalignant skin alteration, which may progress to lentigo maligna melanoma (LMM). LM usually appears as a small dark brown spot in the head and neck region. Over some years it may gradually enlarge to palm size and the colour become more motley. Histologically many atypical melanocytes are seen in the basal layer of the epidermis and along the adnexal structures, as well as there being dermal elastosis and a lymphohistiocytic inflammatory infiltrate in the superficial dermis. Excision should be performed as soon as the diagnosis is made to avoid more extensive excision, transplantation and development into LMM later on. If transformation of LM into LMM occurs, often after many years, fast growth, increased pigmentation and sometimes a nodular formation are observed. Histologically, the atypical melanocytes have invaded the dermis.

Report of a symposium on: diagnosis and treatment of cutaneous head and neck melanoma.

A series of presentations and discussions was held during a symposium on the diagnosis and treatment of cutaneous head and neck melanoma. The purpose of this meeting was to define certain guidelines on diagnosis and treatment of head and neck melanoma. The results of this symposium are summarized and condensed in this report. Recommendations are made for diagnostic strategies and for treatment. It is indicated that research efforts in immunology need to be expanded to develop rational immunotherapy.

Survival of Danish cancer patients 1943-1987. Malignant melanoma of the skin.

Survival after malignant melanoma in Denmark has improved remarkably in all age groups and people of each sex over the last 30 years. During the study period 1943 87, the proportion of patients presenting with an earlier stage of disease at the time of diagnosis increased. No major change has taken place with respect to treatment. Extent of disease, age and sex exerted a steady influence on survival during the study period. Melanoma patients with localized disease had a far better survival expectancy than those with disseminated disease at the time of diagnosis. Age at time of diagnosis had a clear impact on subsequent survival, younger patients having a better prognosis than older ones. In all age groups, women had a higher relative survival rate than men.