Olli Castrén

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.

Natural history of cervical human papillomavirus (HPV) infections based on prospective follow‐up

Summary. To assess the natural history of human papillomavirus (HPV) lesions in the uterine cervix, a prospective follow‐up of untreated lesions has been conducted since late 1981. The present report summarizes the data on 343 women with cervical HPV lesions currently followed‐up for a mean of 18.7 (SD 15.2) months by colposcopy and PAP smears (group R) or by additional punch biopsy (group A). Initially these tw7o groups were classified on the first PAP smears, presenting with HPV‐induced cytopathic changes, and either with (group A) or without (group B) concomitant changes suggestive of cervical intraepithelial neoplasia (CIN). The clinical course of the HPV lesions could not be predicted adequately from the findings of the first PAP smears, as evidenced by the higher progression rate (154%) in the 214 women initially classified in group B, compared with 116% in the 129 women classified in group A. Furthermore, the number progressing to careinomia in situ requiring conization was equal (seven patients) in the two groups. This necessitated a more flexible approach to follow‐up, permitting transfer of patients between groups, which resulted in a final allocation of 261 women to group A, and 82 to group B. To date, 25% of the total of 343 HPV lesions have regressed. 61% have persisted, and 14% have progressed. Of the latter, a total of 14 (4.1%) have been coned due to progression to carcinoma in situ. The rate of regression seems to be inversely related, and progression directly related. to the degree of HPV‐associated CIN. The results are discussed in the light of the well‐established natural history of classical CIN. Generally recognized as premalignant tesions. The present results, demonstrating that the natural history of cervical HPV lesions is very similar to that o f CIN, further substantiate the concept of HPV lesions as precursors of cervical cancer. With the potential to progress to carcinoma in situ when left untreated.

Human papillomavirus (HPV) DNA sequences demonstrated by in situ DNA hybridization in serial paraffin-embedded cervical biopsies

SummaryAn in situ DNA hybridization technique was used to identify various types of Human papillomavirus (HPV) in paraffin sections of serial punch biopsies taken from 64 patients having colposcopy because of abnormal smears. There women were in fact 64 consecutive patients out of 505 attending our clinic (at 6-month intervals) since 1981 for HPV infections. HPV 6 DNA sequences were found in 20%, HPV 11 in 17%, HPV 16 in 8% and HPV 18 in 5% of the 64 biopsies analysed with this method so far. More than 60% of HPV 6-positive lesions belong to HPV-NCIN (HPV lesion without concomitant CIN) or HPV-CIN I categories, as contrasted with HPV 16-positive lesions, 80% of which belong to HPV-CIN II and III categories. None of the HPV 16- or HPV 18-infected lesions regressed, as contrasted with 23% and 45% in those infected with HPV 6 and HPV 11, respectively (P < 0.01). The rate of progression (38.4% and 45.5%, respectively) was markedly lower in HPV 6- and HPV 11 lesions as compared with that (80%) of HPV 16 lesions. The present results while supporting the concept on HPV 16 and HPV 18 as the high risk HPV types in cervical carcinogenesis also emphasize the applicability of the in situ DNA hybridization as a powerful tool in analysis of the specific HPV DNA sequences in routinely progressed biopsies of these lesions.

Cryotherapy and Co2-Laser Vaporization in the Treatment of Cervical and Vaginal Human Papillomavirus (HPV) Infections

A series of 119 women with Human papillomavirus (HPV) infections of the uterine cervix and/or vagina were included in the present study, where the efficacy of cryotherapy and CO2‐laser vaporization was assessed after a mean follow‐up of 14 months (SD 6 months) after treatment, as related to the natural history of the disease. Routine Papanicolaou (PAP) smears with HPV‐induced changes were the basis for patient recruitment. Patients with cervical HPV lesions (HPV‐NCIN, HPV‐CIN l or II) were randomly allocated into laser (55 women) and cryotherapy (42 women) groups. Women with combined lesions (HPV‐CIN & HPV‐VAIN) were treated by laser (22 patients). The cure rate after laser vaporization was practically identical to that of cryotherapy, 64% and 54%, respectively (difference not statistically significant). The success rate was significantly lower (40%) for the combined lesions (HPV‐CIN & HPV‐VAIN)(p<0.05). The residual disease encountered in patients after the first treatment with cryotherapy and laser was classified as HPV‐NCIN in 78.9% and 37.0%, respectively. The number of patients is still too small to draw reliable conclusions on the effects of these therapy modes, as related to HPV type of lesion (HPV 6, 11, 16, 18, 31 and 33). The cure rates for both cryotherapy and laser in our treatment groups were significantly higher than the spontaneous regression rate (p < 0.001), suggesting that treatment by either cryotherapy or CO2,‐laser vaporization significantly changes the natural history of genital HPV infections. More patients and longer follow‐up are still needed, however, to fully establish the efficacy of the current treatment modalities in gynecological HPV infections.

EFFECT OF ORAL CONTRACEPTIVES ON SERUM FOLIC ACID CONTENT

Thirty healthy women were examined before and after three months treatment with oral contraceptives to see whether the treatment affected the serum folic acid content. Three combined regimens were used. Prior to treatment serum folic acid was 6·0±2·4 ng./ml. and after treatment 5·5±2·2 ng./ml. No difference was noted between drugs containing different oestrogen‐progestagen components. Treatment of longer duration, 5–32 cycles, did not affect serum folic acid levels significantly. The haemoglobin concentration and packed cell volume remained unchanged during the period of treatment.

Lymphocyte β2-adrenoceptor density during menstrual cycle and pregnancy, in delivery and puerperium

Lymphocyte beta 2-adrenoceptor density was determined in 11 women during the normal menstrual cycle and 15 women during normal pregnancy. No significant difference in lymphocyte beta 2-adrenoceptor density was established in this follow-up study during the menstrual cycle or pregnancy. Lower lymphocyte beta 2-adrenoceptor density was established just after delivery and in puerperium compared with that during pregnancy. It is likely that the high catecholamine concentration during parturition together with the duration of labour and delivery caused down-regulation of the beta 2-adrenoceptors. In puerperium the irregular day-rhythm and the stress of caring for the newborn may also have an effect.

Natural Killer (NK) Cells with HNK‐1 Phenotype in the Cervical Biopsies of Women Followed‐Up for Human Papillomavirus (HPV) Lesions

Local immunocompetent cell infiltrates in 263 cervical punch biopsies of women followed‐up since 1981 (16±14 months, M±SD) for an established Human papillo‐mavirus (HPV) lesion with or without concomitant cervical intra‐epithelial neoplasia (CIN) were analysed for presence of human natural killer (NK) cells, defined by the monoclonal antibody HNK‐1 (Leu‐7) using the avidin—biotin peroxidase complex (ABC) technique. HNK‐1 + cells remained at a constant low level (1.8 to 3.0% of the cells) in the different types of HPV lesions (flat, inverted, or papillo‐matous condylomas), their percentages (range 1.3 to 2.5% of cells) remaining similarly unaffected by the severity of associated CIN. As shown to be the case with human NK cell function in the peripheral blood, the percentages of local HNK‐1+ cells did not evidence any age‐dependence. Furthermore, the intensity of the infiltrate did not correlate with the relative levels of HNK‐1 + cells in the biopsies. Slightly (but not significantly) higher levels (2.5%) of HNK‐1+ cells were found in the first biopsies of the HPV lesions found to regress during the follow‐up period (28.8% of cases), when compared with those (1.7% and 1.8%, respectively) in persisting lesions (52.1% of cases) or progressing lesions (19.1% of lesions). the results are discussed in terms of the proposed immune surveillance function of human NK cells in malignant growths, and the conclusion is drawn that the present study does not provide any firm evidence to suggest that local NK cell function would contribute significantly to the clinical behavior of the cervical HPV lesions.

Chlamydial cervicitis in women followed-up for human papillomavirus (HPV) lesions of the uterine cervix.

Abstract. to assess the concomitant appearance of Chla‐mydia trachomatis and Human papilloma virus (HPV) (currently linked with the development of cervical cancer) in uterine cervix, a series of 250 women under continuous observation for cervical HPV lesions (with or without concomitant cervical intra‐epithelial neoplasia (CIN)) were the subject of cervical culturing for C. trachomatis, as well as for IP‐PAP (indirect immunoperoxidase) staining of the cervical biopsies with monoclonal antibody to C. trachomatis. Chlamydia‐positive staining was found in only 2/204 biopsies (0.98%), whereas Chlamydia could be isolated from the cervix of as many as 26/250 (10.4%) women. in repeat cultures, Chlamydia was isolated in 39/936 specimens (4.2%), reflecting the effect of the treatment instituted. the results are discussed in terms of the suggested association of Chlamydia with CIN, as well as of the possible synergism between Chlamydia and HPV in cervical oncogenesis. the conclusion is drawn that Chlamydia and HPV are covari‐ables of sexual behavior, their concomitant appearance in the uterine cervix most probably being ascribable to sexual promiscuity.

Serum Lactic Acid Dehydrogenase and Isoenzymes During Pregnancy and Labor

Total serum lactic acid dehydrogenase activity (LDH) and the levels of LDH isoenzymes were investigated in 14 women during early pregnancy (8–16th week), in 28 women during late pregnancy (29–37th week), in 73 at term (38–42nd week) and in 27 during labor (38–42nd week). LDH activity was found to be elevated in severe pre‐eclampsia and in chronic hypertensive women during pregnancy, as well as during normal and dysfunctional labor. No change was established in total serum LDH during normal pregnancy.

Lactate dehydrogenase isoenzymes in human myometrium during pregnancy and labor

Abstract. Myometrial lactate dehydrogenase isoenzymes were investigated in 32 pregnant women and in 21 women during labor. During pregnancy and labor the H‐type LDH isoenzymes were found to preponderate in contrast to M‐type LDH isoenzymes. Both H‐LDH and M‐LDH isoenzyme activities showed a tendency to increase in normal pregnancy. In severe pre‐eclampsia and in chronic hypertension, the uterine M‐LDH level decreased. In normal labor, M‐LDH activity declined in both the uterine and the rectus abdominis muscles.