Merja Yliskoski

Quality of life and cost-effectiveness of levonorgestrel-releasing intrauterine system versus hysterectomy for treatment of menorrhagia: a randomised trial

BACKGROUND Heavy menstrual blood loss is a common reason for women to seek medical care. The levonorgestrel-releasing intrauterine system (IUS) is an effective medical treatment for menorrhagia. We report a randomised comparison of this approach with hysterectomy in terms of the quality of life of women with menorrhagia and cost-effectiveness. METHODS Of 598 women referred with menorrhagia to five university hospitals in Finland, 236 were eligible and agreed to take part. They were randomly assigned treatment with the levonorgestrel-releasing IUS (n=119) or hysterectomy (n=117). The amount of menstrual blood loss was objectively measured. The primary outcome measure was health-related quality of life at 12-month follow-up. Analyses were by intention to treat. FINDINGS In the group assigned the levonorgestrel-releasing IUS, 24 (20%) women had had hysterectomy and 81 (68%) continued to use the system at 12 months. Of the women assigned to the hysterectomy group, 107 underwent the operation. Health-related quality of life improved significantly in both the IUS and hysterectomy groups (change 0.10 [95% CI 0.06-0.14] in both groups) as did other indices of psychological wellbeing. There were no significant differences between the treatment groups except that women with hysterectomy suffered less pain. Overall costs were about three times higher for the hysterectomy group than for the IUS group. INTERPRETATION The significant improvement in health-related quality of life highlights the importance of treating menorrhagia. During the first year the levonorgestrel-releasing IUS was a cost-effective alternative to hysterectomy in treatment of this disorder.

Vertical transmission of human papillomavirus from infected mothers to their newborn babies and persistence of the virus in childhood

OBJECTIVE The purpose of this study was to determine the potential for human papillomavirus to be transmitted vertically. STUDY DESIGN We started a systematic study of children 0.3 to 11.6 years old born to mothers included in the cohort of 530 women prospectively followed up for genital human papillomavirus infections in Kuopio since 1981. So far 98 children have been examined. The examinations included medical history, clinical examination of the oral cavity and hand warts, and cytologic samples from the oral mucosa for detection of human papillomavirus deoxyribonucleic acid with polymerase chain reaction with subsequent Southern blot hybridization. RESULTS Human papillomavirus deoxyribonucleic acid was found in 31 of the 98 (31.6%) oral scrapings. with MY09 and MY11 human papillomavirus primers, 12 of the 98 were positive for human papillomavirus deoxyribonucleic acid in the electrophoresis gel and in subsequent hybridization. Nineteen of the positive samples were not visible in the gel but become positive when hybridized. At delivery, 5 mothers had genital human papillomavirus infection with the same virus type found in her child. In the additional 11 mothers genital human papillomavirus infection with the same virus type as in the child was diagnosed a few months before or after delivery. Mothers of the 25 children shown to be negative for oral human papillomavirus were also human papillomavirus deoxyribonucleic acid negative at delivery. Minor hyperplastic growths of the oral mucosa were found in 21 of the 98 children (21%). One child had a papilloma where human papillomavirus 16 deoxyribonucleic acid was detected, as was also found in her mothers genital area at delivery. CONCLUSIONS Our results support the concept that an infected mother can transmit human papillomavirus to her child.

Prevalence, incidence, and estimated life-time risk of cervical human papillomavirus infections in a nonselected finnish female population

&NA; The authors derived prevalence and incidence figures for cervical human papillomavirus (HPV) infections in an unselected Finnish population of women aged 22. This paper is an epidemiologic study utilizing the mass‐screening program that has been conducted in Finland for cervical cancer since the early 1960s. The authors estimated the lifetime risk of cervical HPV infections based on the figures in this program and on those derived from a random sample of 2,084 (out of 28,861) routine Papanicolaou (Pap) smears examined in their laboratory. The mass‐screening program was performed between 1985‐1986 focusing on a total cohort of 22‐year‐old women (born in 1963) in Kuopio province. In 1985, 2,013 women were invited of which 1,289 attended. One year later, 1,768 women of those 2,013 were reinvited, and the number of women screened at the second round was 1,069. The routine cervicovaginal Pap smears were taken, including a cell sample from the vagina, exocervix, and endocervix. All smears were screened for the HPV‐induced cytopathic changes by the same cytopathologist. The prevalence of HPV infection among the 22‐year‐old women was about 3% at the beginning of the follow‐up and about 7% one year later. The crude annual incidence was 7.0%. According to the estimates for the life‐time risk, half of the sexually active women would experience at least one HPV infection within 10 years. Up to 79% of the Finnish females would contract at least one HPV infection between ages 20 and 79 years. This indicates that factors, which are poorly understood at the moment, exist that regulate the development of an invasive carcinoma from a CIS lesion.

Exposure of an infant to cervical human papillomavirus infection of the mother is common

OBJECTIVE The purpose of this study was to determine the potential of exposure of an infant to cervical human papillomavirus infection of the mother. STUDY DESIGN Cervical scrapes of the mothers and nasopharyngeal aspirate fluids of their infants were analyzed at the time of delivery. The study included 106 infants born by vaginal delivery or by cesarean section and their 105 mothers. Positive results were confirmed and typed by direct deoxyribonucleic acid sequencing or single-strand conformation polymorphism of the polymerase chain reaction product. RESULTS Both the mothers and her infants samples were positive for the same type of human papillomavirus in 29 mother-infant pairs. Interestingly, five infants born by cesarean section were found to be human papillomavirus deoxyribonucleic acid positive for the same human papillomavirus type as their mother. The overall concordance between human papillomavirus types in the mother and her newborn was 69% (29/42). Regardless of match in types found in the mothers and her infants sample, human papillomavirus deoxyribonucleic acid positivity was found in 39 of all the 106 infants (37%). CONCLUSIONS Our results indicate that the infant of the human papillomavirus-infected mother is exposed to infection even when the cervical infection of the mother is subclinical. The possibility of transplacental exposure has to be considered as well.

Low concordance of genital human papillomavirus (HPV) lesions and viral types in HPV-infected women and their male sexual partners.

Background and Objectives To evaluate the concordance of genital human papillomavirus (HPV) lesions and viral types in HPV-infected women and their male sexual partners. Study Design Examination of 270 consecutive women with abnormal Papanicolaou (Pap) smear and their male partners using colposcopy, peniscopy, surgical biopsy and in situ hybridization (ISH). Polymerase chain reaction (PCR) was used in male cases negative with ISH. Results The highest HPV DNA detection rate in women was in cervical intraepithelial neoplasia (CIN III) lesions (96%), HPV 16 being the most frequent type. Of the males, 193 (71.5%) showed histologically confirmed HPV infection, condyloma acuminata (23 cases) and penile intraepithelial neoplasia (PIN) lesions (20 cases) being invariably ISH positive (87% and 80%, respectively). Subclinical flat lesions (113 cases) were mostly ISH negative (70.3%). Of the 270 couples typed by ISH, both partners were positive in 66 (24.4%) cases, but only 15 (22.7%) of them had the same HPV type in their genital tract. By PCR, only seven new HPV DNA positive cases were detected among 77 men negative by ISH. Conclusion Although some association was seen between intraepithelial neoplasia and high-risk HPV types, the concordance of different HPV types between the sexual partners was extremely low. The female findings were not predictive in searching for the male partners with the high risk HPV types, either. HPV DNA detection rate in men seems to depend on morphology of the HPV lesions.

Factors associated with progression of cervical human papillomavirus (HPV) infections into carcinoma in situ during a long‐term prospective follow‐up

Summary. In the course of a prospective study of 508 women with papillomavirus (HPV) lesions of the uterine cervix, 66 lesions that progressed into carcinoma in situ (CIS) were identified and treated by conization during a mean follow‐up period of 35 months. The lesions were investigated with light microscopy and with in‐situ DNA hybridization using 35S‐labelled probes for HPV 6,11,16,18, 31 and 33. After radical cone treatment, 11 of the 66 women (16‐7%) have presented with a recurrent HPV infection. The recurrence rate increased with the duration of the follow‐up period from <10% at the mean follow‐up of 25 months to 16.7% at the most recent follow‐up at 35 months. Most of these 66 HPV lesions (89%) presented with concomitant CIN in the first punch biopsy, but it is noteworthy that the other 11 % presented without concomitant CIN. HPV DNA of at least one of the six types examined was found in 73% of the first biopsies and it is noteworthy that the so‐called ‘low‐risk’ types, HPV 6 and 11, were found as frequently as the ‘high‐risk’ types, HPV 16 and 18 (18% and 17%, respectively). This would suggest a similarity in the biological behaviour of these two HPV groups. Although the concept of the ‘high‐risk’ and ‘low‐risk’ HPV types may remain at least partially valid, it is imperative to realize that infection by HPV 6 and 11 by no means excludes the possibility for clinical progession into CIS and eventually to an invasive carcinoma.

Smoking impairs human papillomavirus (HPV) type 16 and 18 capsids antibody response following natural HPV infection

The natural history of oncogenic human papillomavirus (HPV) infections results from interactions of the virus, the host, and multiple cofactors. We studied the association between humoral immune response to HPV and smoking in 191 HPV infected women prospectively. Two follow-up samples (first and last) were analysed for serum cotinine levels, IgA and IgG antibodies to HPV16 and 18, and Chlamydia trachomatis using ELISA methods. HPV DNA analyses were also performed, and HPV16/18 antibodies were detectable in 23 of 40 (57.5%) HPV DNA-positive women. We performed age-stratified analyses and found that young smokers were less likely to develop HPV16/18 antibodies than non-smokers (OR: 0.2, 95% CI 0.0–0.9). Furthermore, they had a significantly decreased tendency of maintaining constant HPV16/18 IgG antibody positivity by the end of the follow-up (OR: 0.1, 95% CI 0.0–0.8). Smoking did not affect the development of HPV antibody responses in women over 30 y of age. Our results suggest that smoking may induce impaired antibody response in HPV16/18-infected young women.

Prognostic factors in cervical human papillomavirus infections

A prospective follow-up study, without further treatment, of a series of 528 women with cervical human papillomavirus (HPV) infections was conducted from 1981 to the present, with a mean follow-up time of 60.3 months (standard deviation 25.1 months). The women visited the Outpatient Department of Gynecology, Kuopio University Hospital, Kuopio, Finland at six-month intervals. At each visit, a thorough gynecologic examination, PAP-smear, and colposcopy with or without punch biopsy were performed. Epidemiologic data were collected by questionnaire, and complete follow-up data were available for 480 of the 528 women. Of these 480 cases of HPV infection, 58.3% regressed spontaneously, and clinical progression was detected in 14.8%. To establish the prognostic factors associated with the clinical course of cervical HPV infections, the Cox proportional hazards regression model was applied. In the analysis, five variables were included: age, PAP-smear class, grade of cervical intraepithelial neoplasia (CIN), HPV type, and colposcopic appearance at the first visit. In general, patient age at the time of diagnosis was inversely related to the probability of spontaneous regression (P less than 0.01). CIN II, CIN III and HPV type 16 were the most significant independent prognostic factors for progression of cervical HPV infections (P less than 0.001, P less than 0.0001, and P less than 0.001, respectively). We conclude that whenever HPV 16 DNA is found in the cervical biopsy with any grade of CIN, the lesion should be treated. Similarly, the presence of CIN II and CIN III indicates treatment whether HPV DNA are detected or not.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of hysterectomy or levonorgestrel-releasing intrauterine system on sexual functioning among women with menorrhagia : a 5-year randomised controlled trial

Objective  To compare among women with menorrhagia the effect of hysterectomy or levonorgestrel‐releasing intrauterine system (LNG‐IUS) on sexual functioning .

Combined laboratory and diary method for objective assessment of menstrual blood loss

BACKGROUND To develop an objective measurement system for menstrual blood loss applicable in clinical practice. METHODS One hundred and fifty-six patients were enrolled in a randomized trial of the treatment of menorrhagia in all five gynecology departments of the university teaching hospitals in Finland. Correlation between venous blood hemoglobin concentration (Hb) and absorbance at 564 nm (A564) was investigated in experiments with blood samples. Amount of collected menstrual blood and menstrual diary data were analyzed. RESULT Hb concentration and A564 of the blood were linearly correlated (r=0.99). One hundred and fifty-four women (99%) returned used sanitary protection and menstrual diaries. On average, 12% (range 0-57%) of menstrual blood was lost during collection. The median amount of blood recovered from sanitary protection was 89 ml (range 14-724 ml), with 58% (n=90) of the women exceeding 80 ml per cycle. When the spilled blood was taken into account, the corresponding figures were 104 ml (range 15-724 ml) and 66% (n= 101). CONCLUSIONS The spectrophotometric measurement of venous blood in the conventional alkaline hematin method can be replaced by measurement of Hb concentration. All blood incompletely collected should be recorded. Objective measurement of menstrual blood loss can be applied in routine clinical practice.