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J Paavonen

Publications and source records attributed to J Paavonen.

At least 91 records · Page 5Linked to original sources
PubMed1997

Prospective seroepidemiologic study of human papillomavirus infection as a risk factor for invasive cervical cancer.

BACKGROUND: Major risk factors for invasive cervical cancer include infection with human papillomavirus (HPV), infection with other sexually transmitted pathogens (e.g., Chlamydia trachomatis), and smoking. Since exposures to these risk factors can be related, the contribution of any single factor to cervical carcinogenesis has been difficult to assess. We conducted a prospective study to define the role of HPV infection in cervical carcinogenesis, with invasive cancer as an end point. METHODS: A nested case-control study within a joint cohort of 700,000 Nordic subjects was performed. The 182 women who developed invasive cervical cancer during a mean follow-up of 5 years were matched with 538 control women on the basis of age and time of enrollment. Serum samples taken at enrollment were analyzed for evidence of tobacco use (i.e., cotinine levels); for antibodies against HPV types 16, 18, and 33; and for antibodies against C. trachomatis. Relative risks (RRs) were estimated by use of conditional logistic regression. RESULTS: Presence of antibodies against HPV in serum (seropositivity) was associated with an increased risk of cervical cancer, and adjustment for smoking and for C. trachomatis seropositivity did not affect this finding (RR = 2.4; 95% confidence interval [CI] = 1.6-3.7). HPV16 seropositivity was associated primarily with an increased risk of squamous cell carcinoma (RR = 3.2; 95% CI = 1.7-6.2). In contrast, risk associated with HPV18 seropositivity tended to be higher for cervical adenocarcinoma (RR = 3.4; 95% CI = 0.8-14.9). In populations with a low prevalence of antibodies against C. trachomatis, the HPV16-associated risk of cervical cancer was very high (RR = 11.8; 95% CI = 3.7-37.0); in contrast, in populations with a high prevalence of antibodies against C. trachomatis, no excess risk was found. CONCLUSION: Past infection with HPV16 increases the risk of invasive cervical squamous cell carcinoma, most clearly seen in populations with a low prevalence of sexually transmitted diseases.

Adenocarcinoma↗
PubMed1997

Human papillomavirus in squamous cell carcinoma of the vulva by polymerase chain reaction.

OBJECTIVE: To investigate the prevalence of human papillomavirus (HPV) DNA in squamous cell carcinoma of the vulva by polymerase chain reaction (PCR). METHODS: Archival diagnostic phase biopsies from 74 patients with squamous cell carcinoma of the vulva were investigated for HPV DNA by PCR. We used both consensus primers located in the open reading frame L1 and type-specific primers for HPV 6 (open reading frame E5), HPV 11 (open reading frame L1), HPV 16, HPV 18, and HPV 33 (open reading frame E6). RESULTS: HPV DNA was detected in 27 (36%) of the 74 patients, of whom 19 had HPV 16, nine had HPV 18, one had HPV 33, and one had unclassified HPV DNA. No case of HPV type 6 or 11 was detected. Two squamous cell carcinomas were positive for both HPV 16 and 18, and one was positive for both HPV types 16 and 33. Three squamous cell carcinomas positive for E6 gene using type-specific primers were negative using L1 consensus primers. CONCLUSION: Our PCR methods using both consensus open reading frame L1-derived primers and type-specific open reading frame E6-derived primers of HPV types 16, 18, and 33 seemed to be an appropriate combination for the detection of HPV DNA in archival tissues of vulvar carcinoma. Both HPV types 16 and 18 were associated with squamous cell carcinoma of the vulva, although the prevalence of HPV 16 was considerably lower than in cervical carcinoma. It appears that vulvar and cervical carcinomas are not identical etiologically and that factors other than HPV are important in vulvar carcinogenesis.

Adult↗
PubMed1997

Acute pelvic inflammatory disease: associations of clinical and laboratory findings with laparoscopic findings.

OBJECTIVE: To assess the relation of clinical variables and laboratory data to pelvic laparoscopic observations of tubal occlusion, adnexal adhesions, and peritoneal exudate in women with acute salpingitis. METHODS: Clinical and laboratory evaluations were performed systematically before laparoscopy in 155 women with suspected acute pelvic inflammatory disease (PID), 82% of whom proved to have acute salpingitis confirmed with laparoscopy. Laparoscopic findings were scored in three categories (tubal patency, adhesions, and exudate.) RESULTS: Two general categories of laparoscopic findings were present: 1) tubal occlusion and moderate to severe adhesions in 30 women, and 2) pelvic-abdominal exudate in 27 women. In the remaining 16 women, these laparoscopic findings occurred alone or in other combinations. Among women with acute salpingitis, tubal occlusion was associated positively with older age, palpable adnexal mass, and moderate to severe pelvic adhesions; negative associations were found with abdominal rebound tenderness, mean abdominal-pelvic tenderness score, pelvic-abdominal exudate, and isolation of either Neisseria gonorrhoeae or Chlamydia trachomatis. Moderate or severe pelvic adhesions were associated positively with increased duration of abdominal pain (5 versus 3 days) compared with limited or no pelvic adhesions, but they were associated negatively with mean abdominal-pelvic tenderness score and with pelvic-abdominal exudate (47% versus 73%). Free exudate in the pelvis or abdomen as compared with limited or no exudate was associated positively with abdominal rebound tenderness (86% versus 65%), abdominal-pelvic tenderness score, elevated white blood cell count (83% versus 52%), and recovery of N gonorrhoeae (79% versus 57%). Free exudate was associated negatively with the median duration of pain (3 versus 6 days), oral contraceptive use (4% versus 26%), and palpable adnexal mass (7% versus 25%). Analyses limited to women without a history of PID gave similar results. CONCLUSIONS: Although clinical and laboratory criteria traditionally used to judge the clinical severity of acute PID partially predict the degree of tubal or other pelvic abnormalities among women with acute salpingitis and tend to distinguish those with tubal occlusion or moderate to severe adhesions from those with peritonitis, these criteria have low predictive value and are not reliable in the individual patient.

Acute Disease↗
PubMed1997

Diagnostic phase antibody response to the human papillomavirus type 16 E2 protein is associated with successful treatment of genital HPV lesions with systemic interferon alpha-2b.

BACKGROUND AND OBJECTIVE: Systemic interferon alpha-2b treatment reduces relapses of genital human papillomavirus (HPV) lesions in some but not all females. The aim of the present study was to investigate possible predictive pretreatment factors for the outcome of therapy. MATERIAL AND METHODS: HPV DNA status and HPV antibody response were evaluated in 100 randomized patients treated with laser ablation and systemic interferon alpha-2b or placebo, and followed up to 6 months. RESULTS: Overall, adjuvant therapy with systemic interferon-alpha did not differ from placebo. However, detectable diagnostic phase levels of serum antibodies to e.g. HPV16 open reading frame (ORF) E2 derived peptide 141EEASVTVVEGQVDYY155 predicted 10-fold difference in the risk of recurrence of HPV infection following adjuvant interferon alpha-2b therapy as compared with placebo (odds ratio, OR, 0.5, 95% confidence interval (CI), 0.1-2.3; OR, 4.6, 95% CI 0.5-41, respectively). This trend was statistically significant in the whole study population (2P < 0.05), and in patients with high viral load (2P < 0.01). CONCLUSIONS: Evaluation of the E2 antibody responses may help to identify women with genital HPV lesions who respond to systemic interferon alpha-2b treatment.

Adolescent↗
PubMed1997

Human papillomavirus DNA in urine specimens of men with condyloma acuminatum.

BACKGROUND AND OBJECTIVES: Because warts are often found in the male urethra, human papillomavirus (HPV) may well be present in urine of patients with urethral condylomata. GOAL: To detect HPV DNA in urine specimens of men with condylomata acuminata using polymerase chain reaction. STUDY DESIGN: Forty-seven urine specimens and 25 paraffin-embedded tissues of condylomata acuminata were obtained from men. Of the 47 urine specimens, 29 were from patients with urethral condylomata, 3 from patients with penile condylomata only, and 15 from control subjects without condylomata. Both L1 consensus primers and type-specific primers for-HPV 6, 11, 16, 18, and 33 were used. RESULTS: HPV DNA was detected in 22 of the 29 (76%) urine specimens from patients with urethral condylomata, in none of the 3 urine specimens from patients with penile condylomata, and in none of the 15 controls. Paraffin-embedded tissues of all 25 condylomas were positive for HPV DNA. The HPV types detected in urine were identical to those detected in urethral condylomas. CONCLUSIONS: HPV DNA is present in urine of patients with urethral condylomata. Urine may be used for noninvasive screening of asymptomatic HPV infections of the male genital tract. Detection of HPV DNA in urine may be useful for monitoring the response to treatment of urethral condylomata.

Adult↗
PubMed1997

First-void urine testing for Chlamydia trachomatis by polymerase chain reaction in asymptomatic women.

BACKGROUND: Because Chlamydia trachomatis infections are usually asymptomatic or minimally symptomatic, diagnosis is often delayed. GOAL: To perform a comparative study of first-void urine (FVU) polymerase chain reaction (PCR) testing and endocervical swab antigen testing in the diagnosis of C. trachomatis infection among asymptomatic women. STUDY DESIGN: The study population consisted of 1,090 unselected women attending a family planning clinic or a university student health clinic. Calculations of test performances were based on an expanded reference standard including enzyme immunoassay (EIA) or PCR tests confirmed by direct fluorescence antibody (DFA) test or major outer membrane protein PCR test, respectively. RESULTS: The overall prevalence of C. trachomatis infection was 5.6%. After resolution of discrepant specimens, FVU PCR detected 85% (52/61) and endocervical swab EIA/DFA 90% (55/61) of confirmed positive cases. CONCLUSIONS: These results indicate that the FVU PCR test is an accurate, noninvasive screening method and can replace endocervical swab EIA in the detection of C. trachomatis infection in low-prevalence populations.

Chlamydia Infections↗
PubMed1997

Valaciclovir versus aciclovir in patient initiated treatment of recurrent genital herpes: a randomised, double blind clinical trial. International Valaciclovir HSV Study Group.

OBJECTIVE: To compare the efficacy and safety of twice daily valaciclovir with five times daily aciclovir in the treatment of an episode of recurrent genital herpes simplex virus (HSV) infection in immunocompetent individuals. METHODS: 739 patients with a history of recurrent genital HSV infection received either oral valaciclovir (500 mg twice daily) or aciclovir (200 mg five times daily) for 5-days for treatment of their next recurrent episode in a controlled, randomised, double blind trial. Patients self initiated therapy at the first signs and/or symptoms of the HSV recurrence, then were assessed in clinic on five occasions over 7 days, and twice weekly thereafter until lesions had healed. Safety was evaluated through adverse experience reports and haematology and biochemistry monitoring. RESULTS: No significant differences were detected between valaciclovir and aciclovir for the primary endpoint, the duration of all signs and symptoms which included lesion healing and pain/discomfort. The hazard ratio [95% confidence interval] for valaciclovir v aciclovir was 0.93 [0.79, 1.08]. Lesion healing time was similar in each treatment group (hazard ratio valaciclovir v aciclovir 0.96 [0.80, 1.14]). The odds ratio of valaciclovir v aciclovir in preventing the development of vesicular/ulcerative lesions was 1.08 [0.82, 1.42]. Percentages of patients in whom all HSV cultures were negative were similar in the valaciclovir and aciclovir groups at 59% and 54% respectively; for patients having equal to or more than one positive culture result after treatment initiation, cessation of virus shedding was similarly rapid for the two treatments (hazard ratio 0.98 [0.75, 1.27]). The safety profiles of valaciclovir and aciclovir were comparable with adverse experiences being infrequent and generally mild. CONCLUSION: This study has demonstrated that valaciclovir 500 mg twice daily is equivalent in efficacy to aciclovir 200 mg five times daily as episodic treatment of recurrent genital HSV infection. Valaciclovir maintains the established efficacy and safety of aciclovir but offers a much more convenient twice daily dosing regimen.

Acyclovir↗
PubMed1997

Type 1 cytokine response and treatment outcome of genital HPV lesions.

OBJECTIVES: To determine the role of type 1 cytokines as predictors of response to treatment of genital HPV lesions with laser ablation with or without adjuvant systemic interferon alpha 2b (IFN-alpha). METHODS: Measurement of serum interleukin 2 (IL-2), IL-2 soluble receptor alpha (sIL-2 alpha), interferon gamma, and human papilloma virus (HPV) DNA in patients undergoing treatment of genital HPV lesions with carbon dioxide laser and systemic IFN-alpha. A randomised, placebo controlled study of 92 cases with 6 months of follow up. RESULTS: High IL-2/sIL-2 alpha was associated with 60% to 70% protection against recurrences both in the IFN-alpha and placebo groups (OR = 0.4, 90%, CI 0.1-2.5; OR = 0.3, 90% CI 0.0-1.8, respectively). Diagnostic phase serum IL-2 predicted favourable outcome (OR = 0.2, 90% CI 0.0-1.0) in women with high load of HPV DNA or HPV 16/18 DNA regardless of the adjuvant therapy. CONCLUSIONS: Serum IL-2 determinations may identify women with good prognosis following laser ablation of genital HPV lesions.

Adjuvants, Immunologic↗
PubMed1996

Human papillomavirus DNA in uterine cervix squamous cell carcinoma and adenocarcinoma detected by polymerase chain reaction.

BACKGROUND: Substantial clinical, epidemiologic, and experimental evidence has reinforced the role of high risk human papillomavirus (HPV) types in the development of cervical carcinoma. The authors investigated HPV in the uterine cervix squamous cell carcinomas and adenocarcinomas of Finnish patients. METHODS: Specimens from 352 patients with uterine cervix squamous cell carcinomas and 108 with adenocarcinoma were examined for HPV DNA by polymerase chain reaction. The authors used consensus primers located in the L1 region, as well as HPV16, 18, and 33 type-specific primers located in the E6 region. RESULTS: HPV DNA was detected in 324 of 352 squamous cell carcinomas (92%), and 81 of 108 adenocarcinomas (75%). Two-hundred seventy-four of 352 squamous cell carcinomas (78%) and 18 of 108 adenocarcinomas (17%) contained HPV16 DNA, whereas 55 of 352 squamous cell carcinomas (16%) and 60 of 108 adenocarcinomas (56%) contained HPV18 DNA. Eight squamous cell carcinomas and 4 adenocarcinomas were positive for HPV33. Twenty-eight squamous cell carcinomas and 5 adenocarcinomas were positive for either HPV16 and HPV18 or HPV16 and HPV33. Unclassified HPV DNA was detected in 17 squamous cell carcinomas and 4 adenocarcinomas. Twenty-eight squamous cell carcinomas and 9 adenocarcinomas, which were positive for E6 DNA using type-specific primers, were negative for the L1 gene. All 460 cervical specimens were tested twice with identical results. CONCLUSIONS: HPV DNA was highly prevalent in both uterine cervix squamous cell carcinoma and adenocarcinoma. HPV16 was detected more often in squamous cell carcinoma and HPV18 was detected more often in adenocarcinoma. Both consensus structural L1 gene-derived primers and type-specific viral E6 oncogene-derived primers were necessary to detect HPV DNA in cervical carcinoma.

Adenocarcinoma↗
PubMed1996

Serologically diagnosed infection with human papillomavirus type 16 and risk for subsequent development of cervical carcinoma: nested case-control study.

OBJECTIVE: To study human papillomavirus type 16 in the aetiology of cervical carcinoma. DESIGN: Within a cohort of 18814 Finnish women followed up to 23 years a nested case-control study was conducted based on serological diagnosis of past infection with human papillomavirus type 16. SUBJECTS: 72 women (27 with invasive carcinoma and 45 with in situ carcinoma) and 143 matched controls were identified during the follow up. MAIN OUTCOME MEASURE: Relative risk of cervical carcinoma in presence of IgG antibodies to human papillomavirus type 16. RESULTS: After adjustment for smoking and for antibodies to various other agents of sexually transmitted disease, such as herpes simplex virus type 2 and Chlamydia trachomatis, the only significant association was with infection with human papillomavirus type 16 (odds ratio 12.5; 95% confidence interval 2.7 to 57, 2P<0.001). CONCLUSION: This prospective study provides epidemiological evidence that infection with human papillomavirus type 16 confers an excess risk for subsequent development of cervical carcinoma.

Adolescent↗
PubMed1995

Human T helper cell epitopes overlap B cell and putative cytotoxic T cell epitopes in the E2 protein of human papillomavirus type 16.

Activation of T helper cells is a prerequisite for the function of cytotoxic T lymphocytes (CTL) and the maturation of the B cell response. Because epitopes recognized by each of these cells may overlap, we scanned the E2 protein of human papillomavirus (HPV) type 16 to identify the T helper cell epitopes. Four major T helper cell epitopes (mapping between aa:s 11-25, 141-155, 191-205 & 231-245) and adjacent human B cell epitopes were found. The first peptide-defined epitope (RLNV) 11CQDKILTHYENDSTD25 overlapped five putative HLA-I (A1, A2, A0205, A3 & A11) binding motifs (CQDKILTHY, RLNVCQDKI, NVCQDKIL, RLNVCQDK & RLNVCQDK). This epitope is also part of an N-terminal alpha-helix which may form four HLA-II (DR2, DR4, DR7 & DR8) specific agretopes for structures recognizable by the T cell receptor (e.g. KILT). The second epitope 141EEASVTVVEGOVDYY155 (GLYY) overlapped the putative HLA-A1 & HLA-Bw37 binding motifs (VVEGQVDYY/QVDYYGLYY and EEASVTVV), and two HLA-II (DR1 & DR3) specific agretopes. The third and fourth epitopes were not associated with more than one putative CTL epitope each. Only the first epitope shared considerable aa-homology with corresponding regions of other genital HPV types.

Amino Acid Sequence↗