Jorma Paavonen - Academia.edu (original) (raw)

Papers by Jorma Paavonen

BMJ, Mar 27, 2012

Objectives To determine the effect of human papillomavirus (HPV) quadrivalent vaccine on the risk... more Objectives To determine the effect of human papillomavirus (HPV) quadrivalent vaccine on the risk of developing subsequent disease after an excisional procedure for cervical intraepithelial neoplasia or diagnosis of genital warts, vulvar intraepithelial neoplasia, or vaginal intraepithelial neoplasia. Design Retrospective analysis of data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II)). Setting Primary care centres and university or hospital associated health centres in 24 countries and territories around the world. Participants Among 17 622 women aged 15-26 years who underwent 1:1 randomisation to vaccine or placebo, 2054 received cervical surgery or were diagnosed with genital warts, vulvar intraepithelial neoplasia, or vaginal intraepithelial neoplasia. Intervention Three doses of quadrivalent HPV vaccine or placebo at day 1, month 2, and month 6. Main outcome measures Incidence of HPV related disease from 60 days after treatment or diagnosis, expressed as the number of women with an end point per 100 person years at risk. Results A total of 587 vaccine and 763 placebo recipients underwent cervical surgery. The incidence of any subsequent HPV related disease was 6.6 and 12.2 in vaccine and placebo recipients respectively (46.2% reduction (95% confidence interval 22.5% to 63.2%) with vaccination). Vaccination was associated with a significant reduction in risk of any subsequent high grade disease of the cervix by 64.9% (20.1% to 86.3%). A total of 229 vaccine recipients and 475 placebo recipients were diagnosed with genital warts, vulvar intraepithelial neoplasia, or vaginal intraepithelial neoplasia, and the incidence of any subsequent HPV related disease was 20.1 and 31.0 in vaccine and placebo recipients respectively (35.2% reduction (13.8% to 51.8%)). Conclusions Previous vaccination with quadrivalent HPV vaccine among women who had surgical treatment for HPV related disease significantly reduced the incidence of subsequent HPV related disease, including high grade disease.

Elsevier eBooks, 2020

| Human papillomavirus (HPV) is the most common sexually transmitted infectious agent; its 14 onc... more | Human papillomavirus (HPV) is the most common sexually transmitted infectious agent; its 14 oncogenic types are causally associated with 5-10% of all cancers. The major structural HPV protein self-assembles into immunogenic virus-like particles. Two licensed HPV vaccines-the bivalent vaccine comprising HPV types 16 and 18, and the quadrivalent vaccine comprising HPV types 6, 11, 16 and 18have proven to be safe and efficacious against 6-month-persistent cervical infections of HPV16 and HPV18 and associated precancerous lesions, and both have efficacies of 90-100%. Among baseline HPV-negative adolescent females, vaccine efficacies against the immediate precursor of cervical cancer (intraepithelial neoplasia grade 3) irrespective of HPV type are 93.2% and 43.0% for the bivalent and quadrivalent vaccines, respectively. The quadrivalent vaccine is efficacious (>75% vaccine efficacy) against any of the more-severe precursors of vulval, vaginal and anal cancers. A strong increase in vaccine efficacy with increasing severity of the precancerous lesion is explained by accumulation of the most-oncogenic HPV types 16 and 18 in these lesions. Therefore, prophylactic HPV vaccination will exceed the best results from screening for cancer. With the extremely efficacious prophylactic HPV vaccines, the focus of organized intervention (vaccination and screening) programmes should, however, shift from reducing the HPV disease burden to controlling the prevalence of oncogenic HPV (and nononcogenic HPV) types. Eradication of the major oncogenic HPV types should be pursued.

The Journal of Infectious Diseases, Oct 3, 2013

See the major article by Howell-Jones et al on pages 1397-403.) Background. Public Health England... more See the major article by Howell-Jones et al on pages 1397-403.) Background. Public Health England has reported a decrease of up to 20.8% in new diagnoses of external genital warts (GWs) among women aged <19 years since the national vaccination program with the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine began in 2008. A post hoc analysis of the phase III PATRICIA (PApilloma TRIal against Cancer In young Adults) trial (NCT00122681) was performed to ascertain whether protection against low-risk HPV types was apparent. Methods. Vaccine efficacy (VE) at 48 months was assessed against 6-month persistent infection (6MPI) with lowrisk HPV types in the total vaccinated cohort (TVC) and in the TVC naive (for 25 HPV types tested) populations. Results. In the TVC naive cohort, VE against 6MPI (95% confidence interval) was 34.5% (11.3 to 51.8) for HPV-6/11, 34.9% (9.1 to 53.7) for HPV-6, 30.3% (−45.0 to 67.5) for HPV-11, and 49.5% (21.0 to 68.3) for HPV-74. Conclusions. The HPV-16/18 AS04-adjuvanted vaccine appears to have moderate efficacy against persistent infections with a number of low-risk HPV types (HPV-6/11/74), which are responsible for the majority of external GWs, and recently, antibody and cell-mediated immune response to HPV-6/11 have been observed. These findings may help to explain the decrease in external GW diagnoses seen in England.

The Journal of Infectious Diseases, 2020

Background Human papillomavirus (HPV) vaccination of girls with very high (>90%) coverage has ... more Background Human papillomavirus (HPV) vaccination of girls with very high (>90%) coverage has the potential to eradicate oncogenic HPVs, but such high coverage is hard to achieve. However, the herd effect (HE) depends both on the HPV type and the vaccination strategy. Methods We randomized 33 Finnish communities into gender-neutral HPV16/18 vaccination, girls-only HPV16/18 vaccination, and hepatitis B virus vaccination arms. In 2007–2010, 11 662 of 20 513 of 40 852 of 39 420 resident boys/girls from 1992 to 1995 birth cohorts consented. In 2010–2014, cervicovaginal samples from vaccinated and unvaccinated girls at age 18.5 years were typed for HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59/66/68. Vaccine efficacy for vaccinated girls, HE for unvaccinated girls, and the protective effectiveness (PE) for all girls were estimated. We extended the community-randomized trial results about vaccination strategy with mathematical modeling to assess HPV eradication. Results The HE and PE est...

New England Journal of Medicine, 2007

Background Human papillomavirus types 16 (HPV-16) and 18 (HPV-18) cause approximately 70% of cerv... more Background Human papillomavirus types 16 (HPV-16) and 18 (HPV-18) cause approximately 70% of cervical cancers worldwide. A phase 3 trial was conducted to evaluate a quadrivalent vaccine against HPV types 6, 11, 16, and 18 (HPV-6/11/16/18) for the prevention of high-grade cervical lesions associated with HPV-16 and HPV-18. Methods In this randomized, double-blind trial, we assigned 12,167 women between the ages of 15 and 26 years to receive three doses of either HPV-6/11/16/18 vaccine or placebo, administered at day 1, month 2, and month 6. The primary analysis was performed for a per-protocol susceptible population that included 5305 women in the vaccine group and 5260 in the placebo group who had no virologic evidence of infection with HPV-16 or HPV-18 through 1 month after the third dose (month 7). The primary composite end point was cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, or cervical cancer related to HPV-16 or HPV-18. Results Subjects were followed for an average of 3 years after receiving the first dose of vaccine or placebo. Vaccine efficacy for the prevention of the primary composite end point was 98% (95.89% confidence interval [CI], 86 to 100) in the per-protocol susceptible population and 44% (95% CI, 26 to 58) in an intention-to-treat population of all women who had undergone randomization (those with or without previous infection). The estimated vaccine efficacy against all high-grade cervical lesions, regardless of causal HPV type, in this intention-to-treat population was 17% (95% CI, 1 to 31). Conclusions In young women who had not been previously infected with HPV-16 or HPV-18, those in the vaccine group had a significantly lower occurrence of high-grade cervical intraepithelial neoplasia related to HPV-16 or HPV-18 than did those in the placebo group. (ClinicalTrials.gov number, NCT00092534.

Gynecologic Oncology, 2011

invasion and lymphovascular space invasion are all recorded, as are follow-up data at regular int... more invasion and lymphovascular space invasion are all recorded, as are follow-up data at regular intervals. For this analysis, only adenocarcinomas and SCCs that underwent RVT or RH were included; all other histologic subtypes were excluded. Recurrencefree survival was calculated from the date of surgery, and distributions used the product-limit method of Kaplan and Meier. Differences between medians, proportions and survival curves were compared with the Mann-Whitney U test, the χ 2 test, and the logrank test, respectively. Statistical significance was defined as P < 0.05. Results: Between March 1994 and April 2010, 74 patients with adenocarcinoma of the cervix and 67 patients with SCC underwent RVT with laparaoscopic pelvic lymphadenectomy at one gynecologic oncology center. One hundred eighty-eight cases of adenocarcinoma underwent RH during the same period. Patients undergoing RVT were younger than patients having RH (31 vs 40, P < 0.001). Tumor characteristics were generally similar for the two groups, except depth of invasion and the incidence of high-grade lesions were both higher in the RH group (5 mm vs 3 mm, P < 0.001; and 22% vs 36%, P = 0.04). Adjuvant radiation was given more frequently in the RH group (10.9% vs 2.8%, P < 0.05). Disease-free survival was ultimately similar for the two treatment modalities (see the figure). Disease-free survival was also comparable for patients with adenocarcinomas and SCCs treated by RVT. Conclusions: Radical vaginal trachelectomy is equally efficacious for early-stage adenocarcinoma of the cervix and SCC and is a viable alternative to radical hysterectomy in patients wishing to preserve fertility. In carefully selected cases, disease-free survival is comparable to that of patients undergoing radical hysterectomy, and fewer cases require adjuvant radiation.

Background: We estimated the prevalence and incidence of 14 human papillomavirus (HPV) types (6/1... more Background: We estimated the prevalence and incidence of 14 human papillomavirus (HPV) types (6/11/16/18/31/33/35/39/45/51/52/56/58/59) in cervicovaginal swabs, and the attribution of these HPV types in cervical intraepithelial neoplasia (CIN), and adenocarcinoma in situ (AIS), using predefined algorithms that adjusted for multiple-type infected lesions.Methods: A total of 10,656 women ages 15 to 26 years and 1,858 women ages 24 to 45 years were enrolled in the placebo arms of one of three clinical trials of a quadrivalent HPV vaccine. We estimated the cumulative incidence of persistent infection and the proportion of CIN/AIS attributable to individual carcinogenic HPV genotypes, as well as the proportion of CIN/AIS lesions potentially preventable by a prophylactic 9-valent HPV6/11/16/18/31/33/45/52/58 vaccine.Results: The cumulative incidence of persistent infection with ≥1 of the seven high-risk types included in the 9-valent vaccine was 29%, 12%, and 6% for women ages 15 to 26, 2...

The Journal of Infectious Diseases

Epidemiologic, clinical, molecular and translational research findings support an interrelationsh... more Epidemiologic, clinical, molecular and translational research findings support an interrelationship between Chlamydia trachomatis, pelvic inflammatory disease (PID), and epithelial ovarian cancer (EOC). Overall, the link between C. trachomatis, PID, and EOC seems to be relatively weak, although nondifferential misclassification bias may have attenuated the results. The predominant tubal origin of EOC and the role of chronic inflammation in tumorigenesis suggest that the association is biologically plausible. Thus, C. trachomatis and PID may represent potential risk factors or risk markers for EOC. However, many steps in this chain of events are still poorly understood and need to be addressed in future studies. Research gaps include time of exposure in relation to the long-term consequences and lag time to EOC. Data of differential risk for EOC between chlamydial and nonchlamydial PID is also needed. Another major research gap has been the absence of high-performance biomarkers for ...

American Journal of Obstetrics and Gynecology, 1985

Twenty-seven women with suspected acute pelvic inflammatory disease were studied by laparoscopy a... more Twenty-seven women with suspected acute pelvic inflammatory disease were studied by laparoscopy and endometrial biopsy. Overall, 67% (18 of 27) of the women had acute salpingitis at laparoscopy, 70% (19 of 27) had plasma cell endometritis, and 67% (10 of 15) had an inflammatory cytologic pattern of the peritoneal fluid. In comparison to laparoscopically detected salpingitis, endometritis detected with biopsy had a sensitivity of 89%, a specificity of 67%, a positive predictive value of 84%, and a false negative rate of 22% in the diagnosis of pelvic inflammatory disease. The corresponding figures for inflammation of the peritoneal fluid were 75%, 67%, 90%, and 25%. This study demonstrates that nonpuerperal endometritis is an entity associated with pelvic inflammatory disease, most likely representing an intermediate stage between cervicitis and salpingitis. Endometrial biopsy as an office procedure is a good alternative to laparoscopy in the diagnosis of acute pelvic inflammatory disease and may in fact detect early cases not yet visible at laparoscopy.

Chlamydia, 1989

Perihepatitis, or Fitz-Hugh-Curtis syndrome, is a localized fibrinous inflammation affecting the ... more Perihepatitis, or Fitz-Hugh-Curtis syndrome, is a localized fibrinous inflammation affecting the anterior surface of the liver and the adjacent parietal peritoneum. Perihepatitis, first described by Stajano in 1920, is almost always associated with acute salpingitis. Curtis (1930) described the typical “violin string” adhesions between the liver and the abdominal wall in patients with previous salpingitis.

Journal of Infection, 1992

Cancer Epidemiology, Biomarkers & Prevention, 2010

Background: We describe the incidence and duration of cervical human papillomavirus (HPV) infecti... more Background: We describe the incidence and duration of cervical human papillomavirus (HPV) infection episodes along with the risk of infection reappearance following a period of nondetection. Methods: Women (1,788) ages 16 to 23 years underwent cytologic testing and PCR-based testing of cervical swab samples for HPV DNA (HPV-16/18/31/33/35/45/52/58/59) at ∼6-month intervals for up to 4 years in the context of a phase 3 clinical trial (placebo arm). HPV type–specific incidence rates were estimated per 100 person-years. Duration of type-specific cervical infection episodes and risk of reappearance following a period of nondetection were estimated using Kaplan-Meier methods. Results: HPV-16 exhibited the highest (5.9), and HPV-35 and HPV-33 exhibited the lowest (1.0) incidence rates per 100 person-years. Mean cervical infection durations ranged from 13 months for HPV-59 to 20 months for HPV-16 and 58 (with ongoing infections censored at the time of treatment, if done). The risk of cervi...

Journal of women's health care, 2019

Objectives: Compared to different upright positions, delivery in recumbent position in bed may in... more Objectives: Compared to different upright positions, delivery in recumbent position in bed may increase the likelihood of operative delivery and other delivery complications, and also decrease levels of maternal self-control. A new delivery chair has been developed to facilitate a variety of upright positions during labour. A randomized controlled trial was conducted to evaluate the impact of the delivery chair use on selected obstetrical and neonatal outcomes, compared to traditional recumbent position. Methods: A total of 1477 women with uncomplicated singleton pregnancy ≥ 34 gestational weeks with fetus in vertex presentation were enrolled in the study: 776 in the delivery chair group, and 701 in the control group. Results: An intention-to-treat analysis showed no differences between the groups in any of the outcomes used. Of the women in the delivery chair group, 251 used the chair throughout the second stage. An as-treated analysis was performed between these 251 women and thei...

International Journal of Gynecology & Obstetrics, 2008

Human papillomavirus (HPV) is the causative agent of cervical cancer. Black women are disproporti... more Human papillomavirus (HPV) is the causative agent of cervical cancer. Black women are disproportionally diagnosed and have higher mortality from cervical cancer in the United States. Here we describe the prophylactic efficacy and safety of a quadrivalent HPV-6/11/16/18 vaccine in black women. Methods: A total of 700 black women from Latin America, Europe, and North America (aged 16-24 years) received the vaccine or placebo in one of two studies. Analyses focused on the efficacy and safety of the vaccine. Results: Baseline rates of Chlamydia trachomatis infection and history of past pregnancy were more than twice as high in black women compared with the non-black women who were enrolled in these trials. HPV-6/11/16 or 18 DNA was detected in 18% of black women versus 14.6% in non-black women at day 1. For black women, vaccine efficacy against disease caused by HPV-6/11/16/18 was 100% for cervical intraepithelial neoplasia (0 vs. 15 cases; 95% confidence interval, 64.5%-100%) and 100% for vulvar and vaginal intraepithelial neoplasia and condylomata acuminata (0 vs. 17 cases; 95% confidence interval, 69.3%-100%). There were no serious vaccine-related adverse experiences. A similar proportion of pregnancies resulted in live births (75.8% vaccine; 72.7% placebo) and fetal loss (24.2% vaccine; 27.3% placebo). Conclusions: Prophylactic quadrivalent HPV-6/11/16/18 vaccination of young black women demonstrated high efficacy, safety, and tolerability. HPV vaccination has the potential to reduce cervical cancer-related health disparities both in the United States and around the world.