The vulval vestibular mucosa-morphological effects of oral contraceptives and menstrual cycle.

BACKGROUND: An erythematous and hypersensitive vestibular mucosa has been observed during the use of combined oral contraceptives (COC). Hormonal effects on the vestibular morphology have not been studied. OBJECTIVES: Our aim was to evaluate the morphology of the vulval vestibular mucosa during the influence of COC and during the menstrual cycle. METHODS: Forty-five healthy women (20 using COC and 25 not using COC) were included. A 6-mm punch biopsy was obtained from the right posterior vestibule on days 7-11 of the menstrual cycle. A corresponding biopsy was taken 2 weeks later in 16 women without COC. The epithelial morphology was estimated by measuring interdermal papilla distance, dermal papilla to surface, from basal layer to surface and width of dermal papillae. A histopathological assessment was made. RESULTS: The vulval vestibular mucosa of women using COC displayed a larger distance between the dermal papillae (P = 0.04) and a larger space from the dermal papillae to the epithelial surface (P = 0.03) compared with controls in the follicular phase. Women without COC displayed a larger interdermal papilla distance in the luteal phase compared with the follicular phase, P = 0.02. Histopathology showed more superficial blood vessels in the COC users (P < 0.01). CONCLUSIONS: The vulval vestibular mucosa of women with COC display an altered morphological pattern with shallow and sparse dermal papillae compared with the follicular phase. Similar findings are seen in women without COC during the luteal phase which indicate a gestagenic effect on the mucosa. Associations between the morphological pattern and changes in mucosal mechanical sensitivity require further studies.

HPV type-specific risks of high-grade CIN during 4 years of follow-up: a population-based prospective study.

We followed a population-based cohort of 5696 women, 32-38 years of age, by registry linkage with cytology and pathology registries during a mean follow-up time of 4.1 years to assess the importance for CIN2+ development of type-specific HPV DNA positivity at baseline. HPV 16, 31 and 33 conveyed the highest risks and were responsible for 33.1, 18.3 and 7.7% of CIN2+ cases, respectively. Women infected with HPV 18, 35, 39, 45, 51, 52, 56, 58, 59 and 66 had significantly lower risks of CIN2+ than women infected with HPV 16. After adjustment for infection with other HPV types, HPV types 35, 45, 59 and 66 had no detectable association with CIN2+. In summary, the different HPV types found in cervical cancer show distinctly different CIN2+ risks, with high risks being restricted to HPV 16 and its close relatives HPV 31 and HPV 33.

Vulvovaginal candida in a young sexually active population: prevalence and association with oro-genital sex and frequent pain at intercourse.

OBJECTIVE: To study the prevalence of vulvovaginal candida among sexually active adolescents. To determine past and present symptoms, including pain at intercourse and potential behavioural risk factors associated with vulvovaginal candidiasis. METHODS: At an adolescent centre, 219 sexually active women who underwent genital examination, also completed a questionnaire on a history of genital symptoms and infections, sexual and hygiene habits, and the use of contraceptives. Symptoms and clinical signs were registered. Vaginal samples were analysed for candida species and urine for Chlamydia trachomatis. RESULTS: Candida culture was positive in 42% of the women and only 15% were asymptomatic. A history of recurrent candidiasis was given by 22%. Frequent pain at intercourse was reported by 24% and frequent oro-genital sex by 42% of the women. Frequent pain at intercourse was significantly associated with both the growth of candida and a history of recurrent candidiasis. Oro-genital sex was an independent risk factor for the growth of candida. CONCLUSION: In sexually active adolescents, who underwent genital examination, candida cultures were positive in 42%. The habit of frequent oro-genital sex was associated with the growth of candida. Pain at intercourse was associated with the growth of candida and recurrent candidiasis.

The significance of p53 codon 72 polymorphism for the development of cervical adenocarcinomas.

Infection with the human papillomavirus is an important co-factor in the development of cervical carcinomas. Accordingly, HPV DNA is recognised in most of these tumours. Polymorphism of the p53 gene, codon 72, is also considered a risk factor in the development of cervical carcinoma. However, this finding is contradicted by several observers. In the present investigation, 111 cases of adenocarcinoma of the cervix collected through the Swedish Cancer Registry and 188 controls (females with normal cytology at organised gynaecological screening) were analysed with regard to p53, codon 72, polymorphism using a PCR- and SSCP-based technique. In the controls, 9% showed pro/pro, 44% pro/arg and 47% arg/arg, whereas in the invasive adenocarcinomas, the corresponding figures were 0%, 29% and 71%, respectively. The difference was statistically significant (P = 0.001). HPV DNA was identified in 86 tumours (HPV 18 in 48, HPV 16 in 31 and HPV of unknown type in 7 cases) and 25 tumours were HPV negative. The p53, codon 72, genotypes observed in HPV-positive and HPV-negative cervical adenocarcinomas were not statistically different (P = 0.690). The results indicate that women homozygotic for arg/arg in codon 72 of the p53 gene are at an increased risk for the development of cervical adenocarcinomas. However, this genetic disposition seems to be unrelated to the HPV infection.

Hospital-managed advanced care of children in their homes.

A hospital-managed project for the advanced care of children in their homes (SABH) has been established in Sweden. The aim was to provide an alternative to inpatient paediatric care by providing hospital-at-home care to stable infants and children using mobile units based on advanced information and communication technology. The Karolinska Hospital children's ward and emergency room referred children to SABH care. A medical care plan was drawn up by the physicians and nurses responsible for the patient while in hospital, in conjunction with the parents and the patient. In one year, 350 episodes of care requiring 3000 bed-days were managed by SABH in the children's homes rather than at hospital. Forty-two per cent of the patients were aged less than one year, 41% were between one and six years old, and 17% were older than six years. SABH care was at least 30% cheaper than conventional hospital care and patient satisfaction with the service was high. At the conclusion of the two-year project, the SABH became a permanent unit at the Karolinska Hospital.

The expression of cyclooxygenase 2 and inducible nitric oxide synthase indicates no active inflammation in vulvar vestibulitis.

BACKGROUND: Although women with vulvar vestibulitis syndrome have principal symptoms of inflammation such as local erythema and pain in the mucosa around the vaginal introitus, it is not clear if vestibulitis is an inflammatory condition. Cyclooxygenase 2 and inducible nitric oxide synthase are known to be upregulated during inflammation. The aim of the present study was to analyze the expression of these enzymes in the vestibular mucosa in order to evaluate the inflammatory activity in the tissue. METHODS: Ten women fulfilling Friedrich's criteria of vulvar vestibulitis syndrome and ten control subjects were included in the study. Punch biopsies were obtained from the vestibular mucosa for analysis of cyclooxygenas 2 and inducible nitric oxide synthase, using indirect immunohistochemistry and Western dot-blot analyses. RESULTS: Both methods used showed low expression of cyclooxygenas 2 and inducible nitric oxide synthase in the vestibular mucosa of all women. There was no difference observed between the groups. CONCLUSIONS: There is a low expression of the inflammatory markers cyclooxygenas 2 and inducible nitric oxide synthase in the vestibular mucosa of women with vulvar vestibulitis syndrome as well as in healthy control subjects. The results indicate no active inflammation present and imply that topical corticosteroids in the treatment of vulvar vestibulitis are unfounded.

The role of human papillomavirus in cervical adenocarcinoma carcinogenesis.

Human papillomavirus (HPV) is considered the single most important co-factor in the development of cervical squamous cell carcinomas. Adenocarcinomas of the cervix are also related to HPV, but the correlation is reported to be less pronounced. In the present study, 131 cervical adenocarcinomas were identified through the Swedish Cancer Registry, examined morphologically and then analysed with sensitive polymerase chain reaction (PCR)-based HPV methods for a study of age-related prevalence of HPV. HPV was identified in 64% of the tumours after PCR amplification of the HPV L1 gene only and in 71% following PCR amplification of both the L1 and E6 genes of HPV. HPV 18 was the most prevalent (52%), followed by HPV 16 (33%) and other types of HPV (15%). The prevalence of HPV was shown to be age-dependent. In women younger than 40 years, HPV was present in 89%, whereas in women 60 years and older, HPV was observed in only 43%. The difference was statistically significant, P<0.005. The HPV-positive adenocarcinomas were represented by an age distribution similar to that of cervical squamous carcinomas with a maximum age, in the 40-49 year old group, whereas the frequency of HPV-negative adenocarcinomas increased with age, typical of most carcinomas occurring in elderly women.

Increased blood flow and erythema in the posterior vestibular mucosa in vulvar vestibulitis(1).

OBJECTIVE: To evaluate vascular changes as a possible underlying cause of mucosal erythema in women with vulvar vestibulitis. METHODS: Laser Doppler perfusion imaging was used to map the superficial blood flow in the vestibular mucosa in 20 women with vestibulitis and in 21 healthy control subjects. A possible correlation between perfusion values and graded erythema (1-5) around the vaginal introitus was analyzed. Changes in microvascular density in the posterior part of the mucosa were investigated in sections from ten patients and ten controls by a computer-assisted image-processing program. Induced vasoconstriction of terminal arterioles in the same posterior area was also studied. RESULTS: Significant increases in perfusion values were registered in the posterior parts of the vestibular mucosa in patients compared with controls. The highest blood flow was registered in the posterior fourchette. The most pronounced erythema was also located in the posterior vestibule in the patients. However, there was no significant correlation between perfusion values and degree of erythema in the same individual. The microvascular density or the ability of vestibular arterioles to constrict did not differ between patients and controls. CONCLUSION: Women with vestibulitis have an increased superficial blood flow and erythema in the posterior parts of the vestibular mucosa. The increased perfusion, most probably caused by a neurogenic vasodilatation contributes to, but does not fully explain the erythema. Atrophic changes of the surface epithelium should also be considered in the evaluation of an erythema.

[Vulvar vestibulitis is a condition with diffuse etiology]. / Vulvavestibulit svårbehandlat tillstånd med oklar etiologi.

Vestibulum vulvae is covered by a sensitive mucosa of endodermal origin. The pain syndrome "vulvar vestibulitis", which is frequently occurring in young women, gives rise to intensive pain during sexual intercourse. The diagnosis requires at least six months duration of provoked pain and the presence of red areas in the vestibulum, which are intensely painful to the touch. There is an increased intraepithelial innervation but no active inflammation. The etiology of vulvar vestibulitis is probably multifactorial. Possible trigger mechanisms include repeated use of antibiotics and local treatment of Candida and HPV infections in combination with the use of hormonal contraceptives, frequent use of local substances that may be irritative, lack of arousal, vaginismus and tense pelvic floor muscles. Spontaneous recovery is possible if all treatment is suspended. Other regimens include biofeedback, psychotherapy, tricyclic antidepressants and surgery. There is a 80 per cent success rate after surgery in carefully selected patients.

Uneven distribution of HPV 16 E6 prototype and variant (L83V) oncoprotein in cervical neoplastic lesions.

A previous Swedish study revealed that both prototype and variant HPV16 E6 oncoprotein, occur in about equal numbers in high-grade cervical intraepithelial neoplasia (HCIN), whereas variant HPV16 predominates in invasive cervical squamous carcinoma. Most of the malignant HPV16 variants contain a common mutation, L83V, in the E6 oncoprotein. In the present investigation, 28 HPV16 positive, invasive cervical adenocarcinomas were collected from a total number of 131 adenocarcinomas. These HPV16-positive cases were evaluated with analysis of the E6 gene, using a recently described PCR-SSCP method for identification of the specific mutation (L83V) in the E6 gene. The results obtained were correlated to findings in 103 preinvasive, HCIN, and 31 invasive cervical squamous carcinomas also infected with HPV16. The HPV16 E6 variant L83V was present in 40% of the HCIN lesions, in 54% of the invasive adenocarcinomas, in comparison to 81% of the invasive squamous carcinomas. The difference between HCIN and squamous carcinomas was statistically significant, P < 0.001, whereas the difference between HCIN and invasive adenocarcinomas was not statistically significant, P = 0.604. Prototype HPV16 and its E6 variant L83V are both prevalent in preinvasive and invasive cervical lesions in Swedish women. However, the obvious predominance of HPV16 variant in squamous carcinomas was not seen in adenocarcinomas. A single amino-acid shift in the HPV16 E6 gene appears to result in a different transforming potential in squamous and glandular cervical lesions.

Neurochemical characterization of the vestibular nerves in women with vulvar vestibulitis syndrome.

Women with vulvar vestibulitis syndrome (VVS) have a distinct burning pain provoked by almost any stimuli in the area around the vaginal introitus. In a previous study we observed an increased number of intraepithelial free nerve endings in women with VVS. The aim of the present study was to neurochemically characterize the superficial nerves in the vulvar vestibular mucosa of women with VVS. Immunohistochemical methods were used to detect neuropeptides normally found in various types of nerve fibers. Calcitonin gene-related peptide, which is known to exist in nociceptive afferent nerves, was the only neuropeptide detected in the superficial nerves of the vestibular mucosa. These findings confirm our previous theory that the free nerve endings within the epithelium are nociceptors.

Increased intraepithelial innervation in women with vulvar vestibulitis syndrome.

Women with vulvar vestibulitis syndrome (VVS) suffer from severe pain and discomfort in the area around the introitus at almost any stimulus that causes pressure within the vestibule. In spite of the severe sensory symptoms present in these women, the influence of the peripheral nerves in the vulvar vestibulum has not been clarified before. In this study the nerve supply in the vestibular mucosa in women with VVS and in healthy women free from vulvar symptoms has been revealed by PGP 9.5 immunohistochemistry. The results show a significant increase in the number of intraepithelial nerve endings in women with VVS, indicating an alteration in the nerve supply in the afflicted area.

Follow up of hysteroscopic surgery for menorrhagia.

OBJECTIVE: A retrospective study of short and long term results of transcervical endomyometrial resection for menorrhagia. MATERIAL AND METHODS: Patient data were collected from all 104 premenopausal women who had undergone a transcervical endomyometrial resection due to severe menorrhagia in 1990-95. Almost 40% had submucous fibromas that were resected together with the endometrium. A questionnaire about gynecological symptoms was mailed to all 104 women. Ninety-seven (93%) women answered the questionnaire. RESULTS: The mean follow-up period was 29 months. The following short-term complications were encountered: fluid overload in four, one uterine perforation and one major bleeding. The long-term complications included: three hematometra and one pregnancy ending in a spontaneous abortion. Glandular hyperplasia of the endometrium without atypia was found in two cases, and adenomyosis in 31 (29%) cases. Twenty-one women (21%) became amenorrhoic after the treatment, whereas forty-nine (51%) had minimal menstrual bleeding. Eleven women (11%) suffered from dysmenorrhea. Due to dysmenorrhea and/or persistent menorrhagia thirteen (12.5%) underwent a hysterectomy, generally within one year after the resection. The histological examinations showed adenomyosis in three cases, fibromas in four and fibromas and adenomyosis in three cases. CONCLUSIONS: In our hands hysteroscopic transcervical endomyometrial resection was a safe and effective treatment for menorrhagia in spite of the fact that amenorrhea was not always achieved. However, dysmenorrhea appeared in 11% of the women. The reason for this remains to be studied. Correct selection criteria is important to get optimal results and reduce the treatment failure.

Human papillomavirus. Subclinical and atypical manifestations.

Subclinical HPV infections, together with latent infections, are probably the most likely outcome after exposure to HPV. Subclinical infection is associated with symptoms such as burning, fissuring, and dyspareunia in some patients. Only these patients should be offered treatment. Diagnosing and treating asymptomatic HPV infection cannot be recommended until better knowledge about the infectious potential of the infection in that phase is obtained. Recently, results have been presented showing a median duration of HPV infection of only 8 months, and after 24 months, only 9% of the women studied continued to be infected. This provides the possibility to reassure patients with HPV infection that it is most likely a transient infection, and one should not worry unduly. In light of this knowledge, it seems unwise to diagnose an asymptomatic infection for which no effective treatment is available and for which the natural history and consequences remain unclear; however, if these lesions were found to have the potential to transmit HPV, the patient should be so counseled.

Acetowhitening of the cervix and vulva as a predictor of subclinical human papillomavirus infection: sensitivity and specificity in a population-based study.

OBJECTIVE: To evaluate acetowhite changes of the cervix and vulva as a predictor of human papillomavirus (HPV) infection. METHODS: In this population-based study all women aged 19, 21, 23, and 25 years and registered as living in a primary health care area within the city of Umeå, Sweden were eligible for inclusion. Each participant underwent a gynecologic examination with sampling of epithelial cells for HPV-DNA detection and Papanicolaou smear. Colposcopy was performed 5 minutes after application of 5% acetic acid. A two-step polymerase chain reaction (PCR) technique was employed for HPV-DNA detection. RESULTS: Colposcopy and sampling of epithelial cells could be performed in 535 women. The sensitivity of detection of HPV infection by the acetowhitening of the cervix was 22% (95% confidence interval [CI] 18%, 26%). The specificity of detection of HPV infection by the acetowhitening of the cervix was 90% (95% CI 87%, 93%). The sensitivity of detection of HPV infection by cytology was 13% (95% CI 10%, 16%), and the specificity was 99% (95% CI 98%, 100%). The combination of acetowhitening and cytology did not improve the diagnostic value. CONCLUSION: Acetowhitening of the cervix and vulva has low sensitivity as a predictor of HPV infections as determined by PCR.

The associations between risk behaviour and reported history of sexually transmitted diseases, among young women: a population-based study.

The aim of this study was to determine the associations between risk behaviour and women's reported sexually transmitted diseases (STDs). All the women aged 19, 21, 23 and 25, residing in a specified housing area, were invited to answer a questionnaire regarding their sexual behaviour, smoking and alcohol consumption and previous history of STD. Of the 611 women participating, one out of 4 women had a history of at least one STD. In an univariate analysis, self-reported STD was found to be related to age, having more than 4 lifetime sexual partners, having practised intercourse at first date, inconsistent use of condoms, alcohol consumption of more than 3 bottles of wine per month and smoking. These factors were, however, not independent of each other and when subjected to a multivariate logistic regression analysis 2 factors, i.e. the lifetime number of sexual partners (more than 4 partners vs one; OR 7.94, (3.41-18.50)) and coitus on first date (practised more than once vs never, OR 2.99 (1.55-5.78)) emerged as independently associated with a previous STD.