Etiology of cervical inflammation

We studied the relationships of selected microbial, clinical, demographic, and behavioral variables to mucopurulent cervicitis in two clinical settings, a sexually transmitted disease clinic and a student health clinic. From each clinic, we studied a group of women referred for suspected mucopurulent cervicitis and a representative sample of other women attending the clinic. After the women were stratified by patient group and summary odds ratios for all groups were obtained, mucopurulent cervicitis was most strongly associated with the isolation of Chlamydia trachomatis; other variables associated with mucopurulent cervicitis included the isolation of Ureaplasma urealyticum, Gardnerella vaginalis, and Trichomonas vaginalis, the presence of serum antibody to C. trachomatis, the clinical diagnosis of bacterial vaginosis, and oral contraceptive use (positive associations) or isolation of yeast (negative association). After adjustment for cervical culture results for C. trachomatis, mucopurulent cervicitis was positively associated with oral contraceptive use (p = 0.02) and isolation of U. urealyticum (p = 0.02) and negatively associated with isolation of yeast (p = 0.03). Among women with a positive cervical culture for C. trachomatis, isolation of U. urealyticum was significantly associated with mucopurulent cervicitis, while among the subgroup of women with a negative cervical culture for C. trachomatis and positive serum antibody to C. trachomatis, oral contraceptive use was strongly associated with mucopurulent cervicitis. These results confirm that in both clinical settings C. trachomatis is the major cause of mucopurulent cervicitis. The roles of U. urealyticum, T. vaginalis, G. vaginalis, bacterial vaginosis, and oral contraceptive use in the etiology of mucopurulent cervicitis deserve further study.     

A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection.

BACKGROUND. Human papillomavirus (HPV) has been associated with cervical intraepithelial neoplasia, but the temporal relation between the infection and the neoplasia remains unclear, as does the relative importance of the specific type of HPV, other sexually transmitted diseases, and other risk factors. METHODS. We studied prospectively a cohort of 241 women who presented for evaluation of sexually transmitted disease and had negative cervical cytologic tests. The women were followed every four months with cytologic and colposcopic examinations of the uterine cervix and tests for HPV DNA and other sexually transmitted diseases. RESULTS. Cervical intraepithelial neoplasia grade 2 or 3 was confirmed by biopsy in 28 women. On the basis of survival analysis, the cumulative incidence of cervical intraepithelial neoplasia at two years was 28 percent among women with a positive test for HPV and 3 percent among those without detectable HPV DNA. The risk was highest among those with HPV type 16 or 18 infection (adjusted relative risk as compared with that in women without HPV infection, 11; 95 percent confidence interval, 4.6 to 26; attributable risk, 52 percent). All 24 cases of cervical intraepithelial neoplasia grade 2 or 3 among HPV-positive women were detected within 24 months after the first positive test for HPV. After adjustment for the presence of HPV infection, the development of cervical intraepithelial neoplasia was also associated with younger age at first intercourse, the presence of serum antibodies to Chlamydia trachomatis, the presence of serum antibodies to cytomegalovirus, and cervical infection with Neisseria gonorrhoeae. CONCLUSIONS. Cervical intraepithelial neoplasia is a common and apparently early manifestation of cervical infection by HPV, particularly types 16 and 18.     

Automated prescreening of conventionally prepared cervical smears: a feasibility study.

The feasibility of an automated screening device that will analyze conventionally prepared cervical smears was examined. Consecutive normal and abnormal cervical smears were selected retrospectively and analyzed on a customized microscope imaging workstation system. Specialized image processing, feature extraction, and object classification algorithms were integrated on the imaging workstation to provide an Analysis Score for each slide analyzed. A threshold was set for the Analysis Score, and all slides with a score less than the threshold were classified as normal. Examination of the distribution of the Analysis Score for normal and abnormal cervical smears provided an estimate that 50% of all slides will be sorted as normal, and consequently need no cytologist review. With the Analysis Score threshold set for a 50% sort rate, zero false-negative slides were found in this slide set. This study has shown that a large percentage of slides can be correctly classified as normal while maintaining a high sensitivity to abnormal slides. Given the current workload problems in cytology laboratories, reducing the screening workload by one half will be beneficial. This study has shown that it is now feasible with current technology to provide a clinically useful device to automate screening of conventional cervical smears.     

Development and duration of human papillomavirus lesions, after initial infection

BACKGROUND: To determine the potential value of human papillomavirus (HPV) vaccines, information concerning the incidence and duration of clinically important lesions is needed. METHODS: A total of 603 female university students were followed for a mean duration of 38.8 months. Triannual gynecologic examinations included cervical and vulvovaginal specimen collection for Pap and HPV DNA testing. Women with cytologic evidence of a high-grade squamous intraepithelial lesion (SIL) were referred for colposcopically directed biopsy. RESULTS: Among women with incident HPV infection, the 36-month cumulative incidence of cervical SILs found by cytologic testing (47.2%; 95% confidence interval [CI], 38.9%-56.4%) was higher than that of vaginal SILs (28.8%; 95% CI, 21.3%-38.2%). The median time to clearance of cervical and vaginal SILs was 5.5 and 4.7 months, respectively. Among women with incident HPV-16 or HPV-18 infection, the 36-month cumulative incidence of cervical intraepithelial neoplasia (CIN) grade 2 was 20.0% (95% CI, 10.8%-35.1%), and that of CIN grade 3 was 6.7% (95% CI, 2.5%-17.0%). The 36-month cumulative incidence of clinically ascertained genital warts among women with incident HPV-6 or HPV-11 infection was 64.2% (95% CI, 50.7%-77.4%). CONCLUSIONS: Intraepithelial lesions are common early events among women with incident HPV infection, and the interval between incident HPV-16 or HPV-18 infection and biopsy-confirmed CIN grade 2-3 appears to be relatively short.     

Variant‐specific persistence of infections with human papillomavirus Types 31, 33, 45, 56 and 58 and risk of cervical intraepithelial neoplasia

In our previous study of the etiologic role of oncogenic human papillomavirus (HPV) types other than HPV16 and 18, we observed a significantly higher risk of cervical intraepithelial neoplasia Grades 2–3 (CIN2/3) associated with certain lineages of HPV types 31/33/45/56/58 [called high‐risk (HR) variants] compared with non‐HR variants. This study was to examine whether these intra‐type variants differ in persistence of the infection and persistence‐associated risk of CIN2/3. Study subjects were women who had any of HPV types 31/33/45/56/58 newly detected during a 2‐year follow‐up with 6‐month intervals. For each type, the first positive sample was used for variant characterization. The association of reverting‐to‐negativity with group of the variants and CIN2/3 with length of positivity was assessed using discrete Cox regression and logistic regression, respectively. Of the 598 newly detected, type‐specific HPV infections, 312 became undetectable during follow‐up. Infections with HR, compared with non‐HR, variants were marginally more likely to become negative [adjusted hazard ratio = 1.3; 95% confidence interval (CI), 0.9–1.8]. The adjusted odds ratio associating with the development of CIN2/3 was 3.0 (95% CI, 1.2–7.4) for persistent infections with HR variants for 6 months and 10.0 (95% CI, 3.8–38.0) for persistent infections with HR variants for 12–18 months as compared with the first positive detection of HR variants. Among women with non‐HR variants, there were no appreciable differences in risk of CIN2/3 by length of positivity. Findings suggest that the lineage‐associated risk of CIN2/3 was not mediated through a prolonged persistent infection, but oncogenic heterogeneity of the variants.     

Association of human immunodeficiency virus and anal human papillomavirus infection among homosexual men.

BACKGROUND--A previous study of men with proctitis, proctocolitis, or enteritis showed an association of anal human papillomavirus (HPV) infection with human immunodeficiency virus (HIV) infection. Because anorectal abnormalities may confound an observed association between anal HPV DNA and HIV seropositivity, the present study was undertaken among consecutive homosexual men seeking HIV serologic testing who were unselected for anorectal symptoms. METHODS--Consecutive homosexual men underwent a standardized interview, physical examination, and collection of specimens for HIV serologic testing and detection of anal HPV DNA. RESULTS--Anal HPV DNA was detected in eight (31%) of 26 HIV-seropositive men and in 10 (8%) of 119 HIV-seronegative men (odds ratio, 5.8; 95% confidence interval, 1.1 to 30.1, adjusted for history of sexually transmitted disease, current anorectal symptoms, and age). When men with anorectal symptoms were excluded from the analysis, anal HPV DNA was detected in 27% of seropositive men compared with 8% of seronegative men (odds ratio, 4.4; 95% confidence interval, 1.4 to 13.4). There was no difference between HIV-seropositive and HIV-seronegative men with respect to distribution of type of HPV DNA. Men with group II or III and group IV HIV disease were 4.1 and 10.9 times, respectively, more likely than HIV-seronegative men to have anal HPV DNA detected. CONCLUSIONS--Because HIV-seropositive men appear to be at increased risk for the detection of anal HPV DNA, the natural course of anal HPV infection should be compared among HIV-seropositive and HIV-seronegative homosexual men.