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Pekka Nieminen

Publications and source records attributed to Pekka Nieminen.

At least 19 recordsLinked to original sources
PubMed2006

Significant variation in performance does not reflect the effectiveness of the cervical cancer screening programme in Finland.

AIM: To characterise the variation in performance indicators of the Finnish cervical screening programme by screening laboratory and to assess whether the performance affects cervical cancer incidence. METHODS: Cervical cancer screening data from 1999 to 2003 from six well-established laboratories were used to analyse rates for follow-up recommendations, referrals and histologically confirmed dysplastic lesions. Laboratory-specific cervical cancer incidences for 1954-2003 were assessed using the cancer registry files. RESULTS: Differences in follow-up recommendations were up to 3.1-fold and 2.2-fold in referrals; differences in the rates for CIN1, CIN2 and CIN3+ were up to 4.5-, 4.7-, and 1.5-fold, respectively. Pre-screening incidence rates for cervical cancer varied 1.5-fold by laboratory, with no major differences in the incidence trends since the onset of screening. CONCLUSION: The performance of a cervical screening programme differs by screening laboratory but does not materially affect the overall programme effectiveness. This leads to variation in cost-effectiveness and probably in avoidable adverse effects. In cervical cancer screening studies, the outcome should be selected as closely as possible to the true measure of programme effectiveness, prevented invasive cervical cancers and subsequent deaths.

Adult↗
PubMed2006

Alternative technologies in cervical cancer screening: a randomised evaluation trial.

BACKGROUND: Cervical cancer screening programmes have markedly reduced the incidence and mortality rates of the disease. A substantial amount of deaths from the disease could be prevented further by organised screening programmes or improving currently running programmes. METHODS/DESIGN: We present here a randomised evaluation trial design integrated to the Finnish cervical cancer screening programme, in order to evaluate renewal of the programme using emerging technological alternatives. The main aim of the evaluation is to assess screening effectiveness, using subsequent cancers as the outcome and screen-detected pre-cancers as surrogates. For the time being, approximately 863,000 women have been allocated to automation-assisted cytology, human papillomavirus (HPV) DNA testing, or to conventional cytology within the organised screening programme. Follow-up results on subsequent cervical cancers will become available during 2007-2015. DISCUSSION: Large-scale randomised trials are useful to clarify effectiveness and cost-effectiveness issues of the most important technological alternatives in the screening programmes for cervical cancer.

Adult↗
PubMed2006

Splicing site mutations in dentin sialophosphoprotein causing dentinogenesis imperfecta type II.

Dentinogenesis imperfecta (DGI) type II (OMIM # 125490) is an inherited disorder affecting dentin. Defective dentin formation results in discolored teeth that are prone to attrition and fracture. To date, several mutations have been described in the dentin sialophosphoprotein (DSPP) gene, causing DGI types II and III and dentin dysplasia type II. DSPP encodes two proteins: dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). Here, we describe a mutational analysis of DSPP in seven Finnish families with DGI type II. We report two mutations and five single nucleotide polymorphisms. In one family we found a mutation that has been described earlier in families with different ethnicity, while in six families we found a novel g.1194C>A (IVS2-3) transversion. Bioinformatic analysis of known DSPP mutations suggests that DGI type II is usually caused by aberration of normal splicing.

Child↗
PubMed2006

Prevalence and risk factors of squamous intraepithelial lesions of the cervix among HIV-infected women - a long-term follow-up study in a low-prevalence population.

HIV-infected women have high risk for precancerous lesions of the uterine cervix. We studied the prevalence and risk factors of squamous intraepithelial lesions (SIL) among systematically followed HIV-infected women enrolled from a population with low HIV prevalence. The study population consisted of 108 HIV-infected women enrolled between 1989 and 2003 with a mean follow-up 4.4 years. Risk factors of SIL were assessed based on samples collected during 2000-02. The overall rates of atypical glandular cells of uncertain significance (AGUS), atypical squamous cells of uncertain significance (ASCUS), low-grade SIL (LSIL) and high-grade SIL (HSIL) were 4, 24, 15 and 5%, respectively. Reduced CD4-lymphocyte count was associated with an increased prevalence of SIL, whereas duration of HIV infection (< or > or =5 years), use of antiretroviral medication, or HIV viral load (<50 or > or =50 copies/mL) was not. The cumulative risk of developing SIL after 1 and 5 years was 17% (95% confidence interval [CI] 7-27%) and 48% (95% CI 33-63%), respectively. The cumulative risk of SIL was increased among women younger than 31 years (P = 0.04) as well as in women displaying high initial HIV viral load (P = 0.01). Our results from a low HIV-incidence population re-emphasize the importance of guidelines for cytologic screening of HIV-seropositive women.

Adolescent↗
PubMed2006

[Not Available].

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Journal Article↗
PubMed2005

Risk of cervical and other cancers after treatment of cervical intraepithelial neoplasia: retrospective cohort study.

OBJECTIVE: To study the long term risk of cervical and other cancers after treatment for cervical intraepithelial neoplasia. DESIGN: Retrospective cohort study. SETTING: University Hospital, Helsinki, Finland. PARTICIPANTS: 7564 women treated for cervical intraepithelial neoplasia during 1974 and 2001 and followed up through the Finnish cancer registry until 2003. MAIN OUTCOME MEASURES: Standardised incidence ratio for cervical cancer and other cancers. RESULTS: During follow-up 22 cases of invasive cervical cancer occurred in women treated for cervical intraepithelial neoplasia (standardised incidence ratio 2.8, 95% confidence interval 1.7 to 4.2). The highest risk was during the second decade (10 cases observed: 3.1, 1.5 to 5.7). The standardised incidence ratio for cervical intraepithelial cancer type 1 was 3.1 (1.4 to 6.2) and for type 2 was 3.7 (0.9 to 10.7). CONCLUSIONS: The risk of cervical cancer in the first 20 years after treatment for cervical intraepithelial neoplasia is higher than in the average population. The risk of smoking related cancers is also increased.

Adolescent↗
PubMed2005

Extralaryngeal HPV infections in male patients with adult-onset laryngeal papillomatosis.

Adult-onset laryngeal papillomatosis is a frequently relapsing disease affecting especially males. We studied the history and prevalence of extralaryngeal HPV infections in these patients to find out their susceptibility to HPV. Of adult-onset laryngeal papilloma male patients treated at Helsinki University Central Hospital over 25 years, we examined 50 for clinical findings, examined Pap and cytological samples from the oral mucosa and urethra and biopsied HPV-suspect lesions. Fifteen female sexual partners underwent gynecological examinations. The history of HPV-associated diseases was also determined from age- and sex-matched control subjects. Of the patients, 16% (8) had a history of genital warts and of the controls, 12.5% (6 of 48). A history of skin warts was more common in patients. Their prevalence of genital warts was higher (3 of 50, 6%) than in the general population (1%, earlier study). Prevalence of oral HPV DNA was 8% (4 of 50). Patients' sexual habits were unexceptional except for an over-representation of high-frequency orogenital sex initiated at a mean of 9.7 years before diagnosis. However, a lack of orogenital contact did not protect them from severe laryngeal disease. Patients with adult-onset laryngeal papillomatosis seem to be prone to HPV infections. Primary laryngeal HPV infection in adolescence may remain latent, requiring cofactors to develop into the clinical disease.

Adult↗
PubMed2005

Adenomatous polyposis families that screen APC mutation-negative by conventional methods are genetically heterogeneous.

PURPOSE: One third of families with classical adenomatous polyposis (FAP), and a majority of those with attenuated FAP (AFAP), remain APC mutation-negative by conventional methods. Our purpose was to clarify the genetic basis of polyposis and genotype-phenotype correlations in such families. PATIENTS AND METHODS: We studied a cohort of 29 adenomatous polyposis families that had screened APC mutation-negative by the protein truncation test, heteroduplex analysis, and exon-specific sequencing. The APC gene was investigated for large genomic rearrangements by multiplex ligation-dependent probe amplification (MLPA), and for allelic mRNA expression by single nucleotide primer extension (SNuPE). The AXIN2 gene was screened for mutations by sequencing. RESULTS: Four families (14%) showed a constitutional deletion of the entire APC gene (three families) or a single exon (one family). Seven families (24%) revealed reduced or extinct mRNA expression from one APC allele in blood, accompanied by loss of heterozygosity in the APC region in six (75%) of eight tumors. In 15 families (52%), possible APC involvement could be neither confirmed nor excluded. Finally, as detailed elsewhere, three families (10%) had germline mutations in genes other than APC, AXIN2 in one family, and MYH in two families. CONCLUSION: "APC mutation-negative" FAP is genetically heterogeneous, and a combination of MLPA and SNuPE is able to link a considerable proportion (38%) to APC. Significant differences were observed in clinical manifestations between subgroups, emphasizing the importance of accurate genetic and clinical characterization for the proper management of such families.

Adenomatous Polyposis Coli↗
PubMed2005

A randomised public-health trial on automation-assisted screening for cervical cancer in Finland: performance with 470,000 invitations.

Our objective was to evaluate automation-assisted screening, in comparison to the conventional method, in a routine population-based cervical cancer-screening programme. Our study is based on an individually randomised design involving approximately 160,000 invitees and 110,000 attendees every year. From 1999 to 2001, 471,297 women were invited to attend and 330,445 smears were screened (attendance rate 70.1%), of which 220,254 were tested conventionally and 110,191 were tested using the automation-assisted method. Cytologic Papanicolaou group II findings were reported slightly more often (RR = 1.04) in the automation-assisted method than in the conventional screening arm. There were 1,291 cases of histologically confirmed dysplasia or carcinoma (0.4% of the screened), one-third of which were severe dysplasia or a more severe finding (CIN3+). The detection rates of histologically verified findings were similar between the 2 screening arms. In Finland, the screening programme has been effective. As the detection rates, particularly of CIN3+, were similar between the screening arms, we will continue the automation-assisted method in the routine screening programme. Further follow-up for interval cancer incidence is required, however, to measure if the effect of screening is the same between the arms. A similar evaluation design is feasible to any other major or competing modification of the screening test or other element in the programme.

Adult↗
PubMed2005

Lack of effect of isoflavonoids on the vagina and endometrium in postmenopausal women.

OBJECTIVE: To determine the effects of soy-derived isoflavones on vaginal epithelium and the endometrium. DESIGN: Double-blind, randomized, placebo-controlled crossover trial. SETTING: Outpatient clinic of a university hospital. PATIENT(S): Sixty-four postmenopausal women with a history of breast cancer. INTERVENTION(S): The women took (in a randomized order) 114 mg of isolated isoflavonoids or placebo in tablets daily for 3 months; the treatment regimens were crossed over after a 2-month washout period. The subjects were studied before and on the last day of each treatment period. MAIN OUTCOME MEASURE(S): Vaginal dryness, maturation index (MI) of vaginal epithelium, endometrial thickness, histology, and expression of estrogen (E) and progesterone (P) receptors and the proliferation marker Ki-67 in the endometrium. RESULT(S): Isolated isoflavones did not relieve vaginal dryness. Maturation index values remained unchanged during the isoflavone regimen, but decreased during the placebo regimen. No changes were found in any of the variables measured in the endometrium. CONCLUSION(S): Daily administration of 114 mg of isolated isoflavones for 3 months had no effect on the subjective perception of vaginal dryness or on objective findings in the vagina or endometrium. This implies safety with regard to the endometrium.

Adult↗
PubMed2004

Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer.

Wnt signaling regulates embryonic pattern formation and morphogenesis of most organs. Aberrations of regulation of Wnt signaling may lead to cancer. Here, we have used positional cloning to identify the causative mutation in a Finnish family in which severe permanent tooth agenesis (oligodontia) and colorectal neoplasia segregate with dominant inheritance. Eleven members of the family lacked at least eight permanent teeth, two of whom developed only three permanent teeth. Colorectal cancer or precancerous lesions of variable types were found in eight of the patients with oligodontia. We show that oligodontia and predisposition to cancer are caused by a nonsense mutation, Arg656Stop, in the Wnt-signaling regulator AXIN2. In addition, we identified a de novo frameshift mutation 1994-1995insG in AXIN2 in an unrelated young patient with severe tooth agenesis. Both mutations are expected to activate Wnt signaling. The results provide the first evidence of the importance of Wnt signaling for the development of dentition in humans and suggest that an intricate control of Wnt-signal activity is necessary for normal tooth development, since both inhibition and stimulation of Wnt signaling may lead to tooth agenesis. Our findings introduce a new gene for hereditary colorectal cancer and suggest that tooth agenesis may be an indicator of cancer susceptibility.

Anodontia↗
PubMed2004

Comparison of HPV test versus conventional and automation-assisted Pap screening as potential screening tools for preventing cervical cancer.

OBJECTIVE: To evaluate new techniques in primary cervical cancer screening programmes. DESIGN: Cross sectional pilot study. SETTING: Department of Obstetrics and Gynaecology, Helsinki University Hospital. POPULATION: Consecutive 2032 human papillomavirus (HPV) DNA and Pap smear samples were taken. Histological diagnoses were obtained from 460 patients. METHODS: We compared the validity of the high risk (HR) HPV DNA detection test to automation-assisted and conventional Pap smear screening. MAIN OUTCOME MEASURES: Specificity and sensitivity of screening methods. RESULTS: Twenty-three percent of women were HPV positive. Forty-five of 46 had high grade lesions and cancers were HR HPV DNA positive, whereas 72/93 of low grade and more severe lesions were HR HPV DNA positive. When histologically verified high grade lesions were observed, the relative sensitivity of HR Hybrid Capture 2 (HR HC2) test was 98% compared with conventional Pap smear and Papnet tests, which performed 54%versus 58%, 83%versus 86% and 93%versus 98% relative sensitivity respectively, using cytological diagnoses HSIL (high grade squamous intraepithelial lesion), LSIL (low grade squamous intraepithelial lesion) or ASCUS (atypical squamous cells of undetermined significance) as the cutoff. The specificity of HC2 test (77-79%) was comparable with the ASCUS+ (ASCUS and more severe) cytology (68-79%), but lower when compared with LSIL+ (91-95%) or especially HSIL+ (97-99%) Pap smear results. CONCLUSION: Pap smear, as a screening test, is very different from HPV DNA detecting test HR HC 2. If cutoff LSIL or more severe lesions is used, primary Pap smear is clearly more specific than HR HC2, but markedly less sensitive. Due to high relative sensitivity of the HPV, only very few histologically confirmed high grade lesions would be detected among HPV negatives using simultaneous cytology. On the other hand, using HPV DNA test alone would lead to multifold amounts of referrals for colposcopy. A posterior Pap smear assessment among HPV positives might be helpful in increasing sensitivity and specificity of screening and defining those who need an immediate referral or treatment. We plan to incorporate primary HR HPV DNA test with posterior Pap smear reading of HPV positives into our ongoing randomised prospective multiarm trial evaluating new techniques in organised screening for cervical cancer in Finland.

Adolescent↗
PubMed2003

Prospective and randomised public-health trial on neural network-assisted screening for cervical cancer in Finland: results of the first year.

Our objective was to evaluate the feasibility and relative validity of interactive neural network assisted screening (Papnet) in primary mass screening for cervical cancer as a public health policy (routine screening). A randomized, ongoing trial involved 152,969 invitees and 108,686 attendees in the organized mass screening in Finland in 1999. Drawing invitations from the population registry, women were randomized 2:1 at an individual level to have their smear analyzed either conventionally or with Papnet. The distribution of smears to different cytological categories, detection rates of dysplasias, in situ carcinomas and cancers were estimated with smears analyzed either conventionally (72,461) or by Papnet (36,225). A total of 108,686 smears were screened and 449 were histologically confirmed as dysplasias and carcinomas. The detection rates for histologically verified carcinoma in situ/severe dysplasia, moderate and mild dysplasias were 0.14%, 0.14% and 0.13% with conventional and 0.14%, 0.14% and 0.11% with Papnet, respectively. The detection rate of invasive cancer was 0.06 per thousand (n = 4) with conventional method and 0.08 per thousand (n = 3) with Papnet. None of the differences were statistically significant (p > 0.05). Papnet was able to identify 92.5% of healthy women (normal cytology), and the specificity of conventional smear was 92.9%. The positive predictive value (Pap Classes III-V) of Papnet was slightly but not significantly better (55% vs. 51%). Papnet screening was feasible as a part of routine screening and performed equally well compared to conventional one methods used in Finland. Organized mass screening was practiced very successfully in the last 38 years. We are going to continue the trial to study the potential trends in cervical cancer incidence in both study arms.

Adult↗
PubMed2003

Quality improvement project in cervical cancer screening: practical measures for monitoring laboratory performance.

BACKGROUND: We conducted a quality improvement project in a cervical cancer screening programme in Helsinki in order to see if detection of precancerous lesions could be influenced by external (participation rate) and internal (laboratory praxis) quality measures. METHODS: In order to increase the participation rate, a second personal invitation to Pap-test was mailed to nonparticipants of the first call. In order to improve the quality of screening, the cytotechnicians monitored their performance longitudinally by recording the number of slides reviewed per day, the pick-up rate of abnormal smears, the report of the consulting cytopathologist, and the number of histologically verified lesions detected from the cases that they had screened. Regular sessions were held to compare the histological findings with the cytological findings of all cases referred for colposcopy. No pressure was applied on the cytotechnicians to ensure that they felt comfortable with their daily workload. RESULTS: A total of 110 000 smears were screened for cervical cancer at the Helsinki City Hospital during 1996-99. Initially, the overall participation rate increased from 62% to 71%. The number of histologically confirmed precancerous lesions (CIN 1-3) more than doubled and their detection rate increased from 0.32% to 0.72%. CONCLUSIONS: Continuous education and feedback from daily work performance were important, yet rather inexpensive means in increasing laboratory performance. Additional measures are needed to further increase the participation rate. Impact of the quality measures on cancer incidence needs to be assessed later on.

Adult↗
PubMed2003

A missense mutation in PAX9 in a family with distinct phenotype of oligodontia.

Mutations in PAX9 have been described for families in which inherited oligodontia characteristically involves permanent molars. Our study analysed one large family with dominantly inherited oligodontia clinically and genetically. In addition to permanent molars, some teeth were congenitally missing in the premolar, canine, and incisor regions. Measurements of tooth size revealed the reduced size of the proband's and his father's deciduous and permanent teeth. This phenotype is distinct from oligodontia phenotypes associated with mutations in PAX9. Sequencing of the PAX9 gene revealed a missense mutation in the beginning of the paired domain of the molecule, an arginine-to-tryptophan amino-acid change occurring in a position absolutely conserved in all sequenced paired box genes. A mutation of the homologous arginine of PAX6 has been shown to affect the target DNA specificity of PAX6. We suggest that a similar mechanism explains these distinct oligodontia phenotypes.

Amino Acid Sequence↗
PubMed2002

Effect of type of screening laboratory on population-based occurrence of cervical lesions in Finland.

The incidence of cervical cancer decreased in Finland over a 30-year period because of an effective screening program, but in the beginning of the 1990s it began to increase. Reasons for such an increase are variable: changes in sexual habits, shortcomings in attendance for screening and possibly variation in laboratory quality. We evaluated the impact of 3 laboratories in the greater Helsinki area on screening performance and on the incidence of invasive cervical cancer and preinvasive cervical lesions in the target population. We studied time trends, geographic differences in attendance and detection rates from screening and the incidence of invasive cancer in the greater Helsinki area (population about 1 million) during the 1990s, when screening was reorganized from the Cancer Society of Finland laboratory to the municipal one (Helsinki) and to a private laboratory (Espoo), while in Vantaa screening remained with the same Cancer Society laboratory. The attendance rate for screening increased during the study period in all 3 cities. The numbers of cytologically suspected and histologically confirmed precancerous lesions found, including severe lesions, decreased significantly with the change of laboratory in Espoo; but in Helsinki and Vantaa, they increased. The overall incidence of invasive cervical cancer increased in all cities in the age groups screened but mostly in Espoo. The rather rapid changes and variation in trends in the number of screening findings cannot be explained by changes in etiologic factors or attendance. They may be related more to the quality of the laboratory performance and perhaps to the criteria used in cytology and colposcopy. A well-organized auditing system is proposed to maintain high quality in screening.

Adult↗
PubMed2002

Regulation of hair follicle development by the TNF signal ectodysplasin and its receptor Edar.

X-linked and autosomal forms of anhidrotic ectodermal dysplasia syndromes (HED) are characterized by deficient development of several ectodermal organs, including hair, teeth and exocrine glands. The recent cloning of the genes that underlie these syndromes, ectodysplasin (ED1) and the ectodysplasin A receptor (EDAR), and their identification as a novel TNF ligand-receptor pair suggested a role for TNF signaling in embryonic morphogenesis. In the mouse, the genes of the spontaneous mutations Tabby (Ta) and downless (dl) were identified as homologs of ED1 and EDAR, respectively. To gain insight into the function of this signaling pathway in development of skin and hair follicles, we analyzed the expression and regulation of Eda and Edar in wild type as well as Tabby and Lef1 mutant mouse embryos. We show that Eda and Edar expression is confined to the ectoderm and occurs in a pattern that suggests a role of ectodysplasin/Edar signaling in the interactions between the ectodermal compartments and the formation and function of hair placodes. By using skin explant cultures, we further show that this signaling pathway is intimately associated with interactions between the epithelial and mesenchymal tissues. We also find that Ta mutants lack completely the placodes of the first developing tylotrich hairs, and that they do not show patterned expression of placodal genes, including Bmp4, Lef1, Shh, Ptch and Edar, and the genes for beta-catenin and activin A. Finally, we identified activin as a mesenchymal signal that stimulates Edar expression and WNT as a signal that induces Eda expression, suggesting a hierarchy of distinct signaling pathways in the development of skin and hair follicles. In conclusion, we suggest that Eda and Edar are associated with the onset of ectodermal patterning and that ectodysplasin/edar signaling also regulates the morphogenesis of hair follicles.

Activins↗