Coexistent chlamydial infections related to natural history of human papillomavirus lesions in uterine cervix.

To assess the role of Chlamydia trachomatis in the development of cervical intraepithelial neoplasia (CIN) and to evaluate possible synergism between chlamydiae and human papillomavirus (HPV) in this process, 418 women who had been prospectively followed up for cervical HPV infections at our clinic since 1981 were tested for chlamydiae. At each visit the patients were examined by colposcopy, and other investigations, such as Papanicolaou (Pap) smears, punch biopsies, urethral, and cervical swabs, were undertaken as indicated. In biopsy specimens the cytopathic changes of HPV, concomitant CIN, and the local immunocompetent cell infiltrates were analysed. The latter were measured and further identified using an alpha naphthyl acetate esterase (ANAE) technique to define B cells, macrophages, and T cells and using monoclonal antibodies to define T cell subsets, NK (natural killer cells), and Langerhans cells. Chlamydial isolation (4.1% in the cervix, and 3.6% in the urethra) did not positively correlate with the degree of cytological atypia in PAP smears or with the degree of CIN lesions associated with HPV. Chlamydial cervicitis did not affect the ANAE definable cell composition of the immunocompetent cell infiltrates in HPV lesions, or that of the immunocompetent cell subsets, including the ratios of T helper to T suppressor cells and the numbers of NK cells. Chlamydial infection did not alter the natural history of HPV lesions, of which 30% regressed, 53% persisted, and 17% progressed during follow up. The present results do not provide evidence to substantiate the hypothesis that chlamydiae and HPV might act synergistically in cervical carcinogenesis, or the view that C trachomatis may be a major aetiological agent of CIN lesions. Chlamydiae and HPV are covariables of sexual behaviour, and their concomitant appearance in sexually promiscuous women is best explained by this fact. As we do not have more direct evidence for the oncogenic potential of C trachomatis (as we have of HPV), it seems reasonable to consider that this agent is not a major cause of CIN, but rather a sexually transmitted agent commonly found in women with CIN because of their promiscuous sexual behaviour.

Electron microscopy in assessment of the biological behavior of human papillomavirus infections in the uterine cervix.

To asses the natural history of human papillomavirus (HPV) infections in uterine cervix, currently implicated in etiology of cervical cancer, a prospective follow-up study has been conducted for 418 women at our clinic since 1981. The present communication summarized the current follow-up data of these patients, with special emphasis on detection of the virus in cervical punch biopsies, as correlated with other characteristics pertinent to the clinical behavior of cervical HPV infections. On each attendance, the patients are subjected to colposcopy accompanied either by Papanicolaou (PAP) smears or punch biopsies. The latter are analyzed for the cytopathic changes of HPV, for concomitant cervical intraepithelial neoplasia (CIN), for HPV structural proteins with IP-PAP technique as well as on transmission electron microscopy (TEM) for the presence of HPV particles. The local immunocompetent cell (ICC) infiltrates are analyzed using ANAE technique to define B cells, MPS cells and T cells and monoclonal antibodies (McAb) for T cell subsets, NK (natural killer) cells and Langerhans cells. HPV particles were disclosed with equal frequency (approx. 65%) in all three types of HPV lesions. Surprisingly, HPV particles were present in 70% of the biopsies derived from the regressed lesions (e. g. in those without histological evidence of HPV lesions), suggesting a possibility of a latent HPV infection. Presence of viral particles did not bear any direct correlations with the expression of HPV antigens, intensity or cellular composition of the ICC infiltrate, defined by ANAE or using McAb. Presence of HPV particles was not a major prognostic determinant, whereas the clinical course was most significantly influenced by the grade of HPV-associated CIN, to which regression was inversely and progression directly related. The results clearly confirm that cervical HPV infections are capable of progressing into carcinoma in situ and thus present with a natural history equivalent to that of classical CIN.

Human papillomavirus (HPV) type as an important determinant of the natural history of HPV infections in uterine cervix.

The present report summarizes our current observations on the natural history of cervical HPV (Human papillomavirus) infections, based on data from 418 women prospectively followed-up in our clinic for a mean of 20 +/- 15 (M +/- SD) months. On each attendance at the clinic (at 6-month intervals), the patients are subjected to colposcopy accompanied by PAP smears and/or punch biopsy, both being analysed for the cytopathic changes of HPV, and for concomitant CIN (cervical intraepithelial neoplasia). In the biopsies, the expression of HPV structural proteins was assessed using an indirect immunoperoxidase (IP-PAP) technique. HPV typing was accomplished by spot hybridization with the DNA probes for HPV 6, 11, 16 and 18. During the follow-up, 24% of the HPV lesions regressed, 55% remained persistent, and 21% progressed, 10.6% having been coned due to progression into CIS. The clinical progression was significantly associated with the grade of HPV-associated CIN. On DNA hybridization, HPV 6 was found in 8%, HPV 11 in 36%, HPV 16 in 11% and HPV 18 in 8% of the 103 lesions typed for HPV DNA so far. HPV-CIN lesions were more frequently than HPV-NCIN associated with HPV 16 and HPV 18, as was the expression of HPV structural proteins. The progression rate was highest (45.5%) in HPV 16 lesions, followed by that (27.3%) in HPV 18 lesions, as contrasted to 0% and 13.3% for HPV 6 and 11, respectively. The natural history of cervical HPV lesions seems to be identical with that of classical CIN lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Factors influencing the biological behaviour of cervical human papillomavirus (HPV) infections in prospectively followed-up women.

To assess the natural history of Human papillomavirus (HPV) infections in uterine cervix, recently linked with cervical intraepithelial neoplasia (CIN), a long-term prospective follow-up study was started at our clinic in 1981. At this writing, a total of 418 women have been followed-up for a mean of 20 +/- 15 (M SD) months. On each attendance (at six-month intervals), the patient is subjected to colposcopy accompanied either by Papanicolaou (PAP) smears or punch biopsies. The latter are analysed for the cytopathic changes of HPV, for concomitant CIN, as well as for HPV structural proteins with IP-PAP technique. The local immunocompetent cell (ICC) infiltrates are analysed using ANAE technique to define B cells, MPS cells and T cells and monoclonal antibodies (McAb) for T cells subsets, NK (natural killer) cells and Langerhans cells. The relative levels of B- and T lymphocytes and MPS cells did not correlate with the clinical course, i.e. regression (RE), persistence (PE) or progression (PR) of the HPV lesions. The same was true with the expression of HPV antigens, intensity of the ICC infiltrate, as well as with the relative levels of NK (HNK-1+) cells and Langerhans (OKT-6+) cells. The T helper/T suppressor cell ratio was subject to minor fluctuations only as determined in three subsequent biopsies, and did not bear any meaningful relationship to the natural history of the HPV lesions. During the follow-up, 24.0% of the HPV lesions regressed, 54.9% remained persistent, and 21.1% progressed, 26 (6.2%) having been coned due to progression into CIS. The clinical course was most significantly influenced by the grade of HPV-associated CIN, to which RE was inversely and PR directly related. The results clearly confirm that cervical HPV infections are capable of progressing into CIS and thus show a natural history equivalent to that of classical CIN. Therefore, cervical HPV infections should be regarded as truly precancerous lesions, which should be examined, treated and followed-up with the same concern as the classical CIN.