IL-17C is a driver of damaging inflammation during Neisseria gonorrhoeae infection of human Fallopian tube.

The human pathogen Neisseria gonorrhoeae ascends into the upper female reproductive tract to cause damaging inflammation within the Fallopian tubes and pelvic inflammatory disease (PID), increasing the risk of infertility and ectopic pregnancy. The loss of ciliated cells from the epithelium is thought to be both a consequence of inflammation and a cause of adverse sequelae. However, the links between infection, inflammation, and ciliated cell extrusion remain unresolved. With the use of ex vivo cultures of human Fallopian tube paired with RNA sequencing we defined the tissue response to gonococcal challenge, identifying cytokine, chemokine, cell adhesion, and apoptosis related transcripts not previously recognized as potentiators of gonococcal PID. Unexpectedly, IL-17C was one of the most highly induced genes. Yet, this cytokine has no previous association with gonococcal infection nor pelvic inflammatory disease and thus it was selected for further characterization. We show that human Fallopian tubes express the IL-17C receptor on the epithelial surface and that treatment with purified IL-17C induces pro-inflammatory cytokine secretion in addition to sloughing of the epithelium and generalized tissue damage. These results demonstrate a previously unrecognized but critical role of IL-17C in the damaging inflammation induced by gonococci in a human explant model of PID.

Diagnostic Value and Clinical Application of Diffusion-Weighted Magnetic Resonance Imaging for Female Pelvic Lesions.

Pelvic inflammatory disease refers to a group of infectious diseases of the female upper genital tract, often caused by ascending infection of vaginitis and cervicitis, causing endometritis, salpingitis, tubo-ovarian abscess, pelvic connective tissue inflammation, and/or pelvic peritonitis. PID is the most common and important infectious disease in nonpregnant women of childbearing age, and inflammation in multiple parts often coexists and affects each other. The functional MRI techniques currently used in pelvic floor muscle injury are magnetic resonance diffusion tensor imaging, T2 mapping, and magnetic resonance elastography. Diffusion tensor imaging is a new imaging and postprocessing technology developed on the basis of magnetic resonance diffusion-weighted imaging. Due to the lack of specificity of clinical symptoms, many subclinical patients are often not detected and diagnosed in time, so it is very difficult to accurately estimate the incidence of PID. This article retrospectively analyzed 72 patients with pelvic inflammatory disease confirmed by surgical pathology from February 2020 to 2022, who had undergone pelvic MRI examination before surgery, including 25 patients with chronic pelvic inflammation (hydrosalpinx), 25 patients with acute pelvic inflammation, and 47 cases (including 21 cases of hydrosalpinx, 19 cases of tubo-ovarian abscess, and 7 cases of pelvic abscess). The age range was 13 to 59 years old. The clinical data and MRI findings were analyzed, the ADC value of the cystic part of the lesion was measured, and the differences in age, maximum diameter of the lesion, thickness of the vessel wall/separation, and the ADC value of the cystic part of chronic and acute pelvic inflammation were compared. In this part of the cases, there were 25 cases of chronic pelvic inflammation and 47 cases of acute pelvic inflammation. The average ADC value of the cystic component of chronic inflammation was significantly higher than that of acute inflammation, which were (2.86 ± 0.20) × 10-3 mm2/s and (1.07 ± 0.38) ×10-3 mm2/s, respectively, P value <0.001.

Isolated Eosinophilic Myometritis: A Case Report of an Extremely Rare Phenomenon.

Increased number of eosinophils in the uterus has been reported under physiological and pathologic conditions. However, eosinophilic infiltration limited to the myometrium is very unusual. A rare finding of isolated eosinophilic infiltration in the myometrium without involvement of endometrium or pathologies in the cervix or ovaries was observed in a 31-yr-old woman seeking medical attention for unexplained infertility, abnormal uterine bleeding, and dysmenorrhea. The patient had no allergies, parasitic disease, or other systemic disorders. This rare manifestation of eosinophilic infiltration expands the differential diagnosis of inflammatory conditions of the myometrium in patients with gynecological issues.

Elevated peritoneal soluble endoglin and GDF-15 in infertile women with severe endometriosis and pelvic adhesion.

OBJECTIVES: Chronic inflammation and pelvic adhesion play a critical role in endometriosis-related infertility. Research studies suggest that TGF-ß superfamily members, such as soluble endoglin (sEng), growth differentiation factor 15 (GDF-15) and tumor growth factor-beta (TGF-ß1) contribute to the regulation of inflammation, angiogenesis and cell adhesion. The objective of this study is to investigate the association between the concentrations of these TGF-ß-related members and the clinical parameters of infertile women with endometriosis. MATERIALS AND METHODS: Sixty-five infertile women who underwent laparoscopy were divided into two groups in this study: those who had endometriosis (n = 33) and control subjects with benign gynecologic disorders (n = 32). The levels of TGF-ß- related members in peritoneal fluid and serum were evaluated by the enzyme-linked immunosorbent assay (ELISA). Clinical and hematological parameters were documented and analyzed. RESULTS: Endometriosis cases had significantly higher levels of sEng, GDF-15 and TGF-ß1 in peritoneal fluid (p<0.0005) compared to control subjects, but not in serum. Moreover, serum GDF-15 level was significantly elevated in the late-stage endometriosis compared to the early-stage group. The levels of three TGF-ß related molecules in peritoneal fluid showed positive correlations with rASRM score. Blood neutrophil counts have correlation with the peritoneal sEng concentration. CONCLUSION: Our novel evidence on the elevated concentration of peritoneal sEng and GDF-15 in endometriosis, specifically in the late-stage, may indicate the essential role of TGF-ß-dependent signaling in endometriosis. Serum GDF-15 might serve as a candidate biomarker for endometriosis severity. Further studies are warranted to investigate the role and regulation of these molecules in endometriosis.

Anti-inflammatory effect of traditional Chinese medicine preparation Penyanling on pelvic inflammatory disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Penyanling is made up of Smilacis Glabrae Rhizoma (SG, from Smilar glabra Roxb.), Angelicae Sinensis Radix (AS, from Angelica sinensis (Oliv.) Diels), Salviae Miltiorrhizae Radix et Rhizoma (SM, from Salvia miltiorrhiza Bunge), Sargentodoxae Caulis (SC, from Sargentodoxa cuneata (Oliv.) Rehd.et Wils.), Linderae Radix (LR, from Lindera aggregata (Sims) Kosterm.), Paeoniae Radix Rubra (PR, from Paeonia lactiflora Pall.), Sparganii Rhizoma (SR, from Sparganium stoloniferum (Graebn.) Buch.-Ham.), Corydalis Rhizoma (CoR, from Corydalis yanhusuo W. T. Wang), Cyperi Rhizoma (CyR, from Cyperus rotundus Linn.), Glycyrrhizae Radix et Rhizoma (GR, from Glycyrrhiza uralensis Fisch.), and Patrinia Scabiosaefolia (PS, from Patrinia scabiosaefolia Fisch. ex Trev.) recorded in Chinese Pharmacopoeia. It has been used on pelvic inflammatory disease (PID) for more than twenty years. AIM OF THE STUDY: This study was carried out to illustrate its pharmacological action and clarify its substantial composition. MATERIALS AND METHODS: The anti-inflammatory effects of Penyanling were studied on a PID rat model and a lipopolysaccharides (LPS)-stimulated THP-1 cell line. Histological changes and levels of inflammatory factors in the uterine tube of the PID rat were examined. Levels of nuclear factor-kappa B (NF-κB) in the nuclear of THP-1 cells and NF-κB, IκB-α, and FPR2 in the cytoplasm were tested by Western blot analysis. Substances within Penyanling were scanned with liquid chromatography-quadrupole-time of flight-mass spectrometry (LC-Q-TOF-MS). The contents of total flavonoids, phenolics, and saponins were quantified. RESULTS: The anti-inflammatory effects of Penyanling were observed on PID rats, such as suppressing the infiltrations of lymphocytes and neutrophils in the uterine tube, decreasing the release of interleukin (IL)-1ß, IL-6, IL-8, and monocyte chemotactic protein (MCP)-1, and promoting the production of lipoxin A4 (LXA4). On the other hand, Penyanling regulated the activity of NF-κB signal pathway on the LPS-stimulated THP-1 cell line, which suggested the potential mechanism of its anti-inflammatory effect. Besides, it could promote the expression of formyl peptide receptor 2 (FPR2), which suggested its effect on enhancing the resolution of inflammation. Seventy-six substances were identified by their accurate molecular weights, mass fragment patterns, retention times, and standards if available. Most of these substances were flavonoids, phenolics, saponins, and alkaloids. The contents of total flavonoids, phenolics, and saponins within Penyanling were 0.186, 1.371, and 4.321 mg/mL, respectively. CONCLUSION: Penyanling showed an anti-inflammatory effect on PID, and its potential mechanism involved suppressing NF-κB signal pathway and promoting the resolution of inflammation. The main substances within it were flavonoids, phenolics, saponins, and alkaloids.

Xanthogranulomatous Salpingitis.

There are approximately a dozen cases of xanthogranulomatous salpingitis reported in the literature, mostly as case reports. Thirteen such cases were identified from 2003 to 2018 at our institution. Patient's ages ranged from 21 to 75 yr old (median and mean, 49 yr). Clinical presentations and surgical indications included pelvic inflammatory disease (5 cases), endometrial carcinoma (4 cases), suspicion of ovarian malignancy (1 case), symptomatic fibroids (1 case), endometriosis (1 case), and infertility (1 case). Surgical-pathologic correlation resulted in diagnoses of tubo-ovarian abscess (4 cases), ovarian abscess (2 cases), pyosalpinx (2 cases), and chronic endometritis (2 cases). Of the remaining 3 cases, 2 presented clinically as pelvic inflammatory disease and the other was seen in the context of an endometrial carcinoma. In summary, this case series from a single institution shows that xanthogranulomatous salpingitis is an uncommon form of chronic inflammation that may be diagnosed from reproductive to menopausal age. With one exception, the cases in this series represent pelvic inflammatory disease despite variable clinical presentations. Pseudoxanthomatous salpingitis should be in the differential diagnosis.

Douching, Talc Use, and Risk for Ovarian Cancer and Conditions Related to Genital Tract Inflammation.

BACKGROUND: Douching is associated with disorders involving genital tract inflammation and genital talc use with epithelial ovarian cancer (EOC), but their joint effects are infrequently considered. METHODS: From 2,040 cases of EOC and 2,100 controls enrolled in eastern Massachusetts and New Hampshire, we used unconditional logistic regression to estimate risk for EOC associated with douching and/or talc use. In subsets of cases and controls, we also collected information about pelvic inflammatory disease (PID), ectopic pregnancy, and cervical neoplasia to estimate risk for these events from douching and/or talc use. RESULTS: The adjusted OR and 95% confidence interval (CI) for all EOC was 0.94 (0.76-1.16) in women who douched but never used talc and 1.28 (1.09-1.51) in women who used talc but never douched. Compared with women who never regularly douched or used talc, ORs (95% CIs) were 0.83 (0.52-1.33) for women who both used talc and homemade douches and 1.53 (1.11-2.10) for women who both used talc and store-bought douches. Cases who both douched and used talc were more likely to have had PID compared with cases who had used neither [OR = 5.03 (95% CI, 1.61-15.7)]. CONCLUSIONS: Douching is not an independent risk factor for ovarian cancer, but the combination of talc use and store-bought douches may modestly increase the risk for EOC beyond that for talc use alone. IMPACT: The joint effect of talc use and douching, especially with commercial products, should be considered in evaluating risks associated with disorders involving genital tract inflammation or EOC.

Chlamydia trachomatis in women with pelvic inflammatory disease (PID): report from a tertiary center in eastern Nepal.

Chlamydia trachomatis is an important agent of pelvic inflammatory disease (PID) globally. Laboratory diagnosis, which is vital for early and appropriate treatment, remains a challenge in resource-limited settings. Our study was undertaken to detect C. trachomatis in women with clinical features of PID. Three endocervical swabs, each obtained from 100 women clinically diagnosed with PID, were subjected to C. trachomatis antigen detection, microscopy and bacteriological culture. Logistic regression was used to assess the risk factors associated with PID. C. trachomatis antigen was present in 6%. The use of hormonal contraception, previous history of PID and a smoking habit were found to have statistically significant association in those who tested positive. Adjunctive use of rapid Chlamydia antigen test with a routinely practiced syndromic approach is beneficial for timely and appropriate antimicrobial therapy in women with PID.

Pathogenesis of Neisseria gonorrhoeae and the Host Defense in Ascending Infections of Human Fallopian Tube.

Neisseria gonorrhoeae is an obligate human pathogen that causes mucosal surface infections of male and female reproductive tracts, pharynx, rectum, and conjunctiva. Asymptomatic or unnoticed infections in the lower reproductive tract of women can lead to serious, long-term consequences if these infections ascend into the fallopian tube. The damage caused by gonococcal infection and the subsequent inflammatory response produce the condition known as pelvic inflammatory disease (PID). Infection can lead to tubal scarring, occlusion of the oviduct, and loss of critical ciliated cells. Consequences of the damage sustained on the fallopian tube epithelium include increased risk of ectopic pregnancy and tubal-factor infertility. Additionally, the resolution of infection can produce new adhesions between internal tissues, which can tear and reform, producing chronic pelvic pain. As a bacterium adapted to life in a human host, the gonococcus presents a challenge to the development of model systems for probing host-microbe interactions. Advances in small-animal models have yielded previously unattainable data on systemic immune responses, but the specificity of N. gonorrhoeae for many known (and unknown) host targets remains a constant hurdle. Infections of human volunteers are possible, though they present ethical and logistical challenges, and are necessarily limited to males due to the risk of severe complications in women. It is routine, however, that normal, healthy fallopian tubes are removed in the course of different gynecological surgeries (namely hysterectomy), making the very tissue most consequentially damaged during ascending gonococcal infection available for laboratory research. The study of fallopian tube organ cultures has allowed the opportunity to observe gonococcal biology and immune responses in a complex, multi-layered tissue from a natural host. Forty-five years since the first published example of human fallopian tube being infected ex vivo with N. gonorrhoeae, we review what modeling infections in human tissue explants has taught us about the gonococcus, what we have learned about the defenses mounted by the human host in the upper female reproductive tract, what other fields have taught us about ciliated and non-ciliated cell development, and ultimately offer suggestions regarding the next generation of model systems to help expand our ability to study gonococcal pathogenesis.

Rare cause of ovarian mass.

Pelvic actinomycosis is a rare entity that occurs almost exclusively in women, the presentation of which is usually non-specific and variable. Pelvic actinomycosis is almost always associated with the use of an intrauterine contraceptive device (IUD). Pelvic actinomycosis unrelated to IUD use is almost always associated with previous surgical procedures. The symptoms, clinical signs and radiological findings are usually non-specific, mimicking an ovarian malignancy. So an awareness of this rare condition and a proper diagnosis can avoid unnecessary surgeries because these cases can be treated with a prolonged course of antibiotics. We present a case of pelvic actinomycosis which masqueraded as an ovarian malignancy.

Safety and efficacy of tigecycline in complicated and uncomplicated pelvic inflammatory disease.

OBJECTIVE: Tigecycline is a glycylcycline antimicrobial structurally related to minocycline, with a wide spectrum of activity that includes anaerobes and typical and atypical microorganisms causing pelvic inflammatory disease (PID). This study aimed to evaluate efficacy and safety of tigecycline in complicated PID and un-complicated PID after the failure of first-line antibiotic therapy. PATIENTS AND METHODS: Between May 2014 and April 2016 at the 2nd Unit of Obstetrics and Gynecology, Santa Chiara Hospital of Pisa a pilot study on 20 women with mild/moderate PID after the failure of first-line antibiotic therapy and on 8 women with complicated PID was conducted. The treatment protocol was 10-day course of tigecycline, with a loading dose of 100 mg intravenously (i.v.) at day one and then 50 mg IV twice daily. The primary endpoint was to evaluate tigecycline's efficacy in terms of clinical response to test-of-cure (TOC) at the end of therapy and 30 days after the last dose. Clinical response during therapy and safety were analyzed as well. RESULTS: A total of 28 women were enrolled, and 25 patients completed the study protocol, because 3 patients reported adverse drug effects resulting in treatment interruption. PID was mainly caused by Chlamydia, Gardnerella, Mycoplasma/Ureaplasma. Tigecycline showed a 100% remission of signs and symptoms in patients resistant to first-line antibiotic regimen and in patients with complicated PID. Moreover, tigecycline showed good tolerability and compliance. CONCLUSIONS: Despite the limited sample size, tigecycline seemed an effective and safe treatment for women with complicated/resistant PID. Nevertheless, further clinical trials are needed to confirm these results.

The obesogen tributyltin induces abnormal ovarian adipogenesis in adult female rats.

Tributyltin chloride (TBT) is an obesogen associated with various metabolic and reproductive dysfunctions after in utero exposure. However, few studies have evaluated TBT's obesogenic effect on adult ovaries. In this study, we assessed whether TBT's obesogenic effects resulted in adult ovarian adipogenesis and other reproductive abnormalities. TBT was administered to adult female Wistar rats, and their reproductive tract morphophysiology was assessed. We further assessed the ovarian mRNA/protein expression of genes that regulate adipogenesis. Rats exposed to TBT displayed abnormal estrous cyclicity, ovarian sex hormone levels, ovarian follicular development and ovarian steroidogenic enzyme regulation. Rats exposed to TBT also demonstrated abnormal ovarian adipogenesis with increased cholesterol levels, lipid accumulation, and PPARγ, C/EBP-ß and Lipin-1 expression. A negative correlation between the ovarian PPARγ expression and aromatase expression was observed in the TBT rats. Furthermore, TBT exposure resulted in reproductive tract atrophy, inflammation, oxidative stress and fibrosis. Ovarian dysfunctions also co-occurred with the uterine irregularities. Abnormal ovarian adipogenic markers occurring after TBT exposure may be associated with uterine irregularities. A positive correlation between the ovarian cholesterol levels and uterine inflammation was observed in the TBT rats. These findings suggest that TBT leads to ovarian obesogenic effects directly by abnormal adipogenesis and/or indirectly through adult reproductive tract irregularities.

Impact of the Levonorgestrel-Releasing Intrauterine System on the Progression of Chlamydia trachomatis Infection to Pelvic Inflammatory Disease in a Baboon Model.

Background: Understanding the relationship between the levonorgestrel (LNG)-releasing intrauterine system (IUS) and sexually transmitted infections (STIs) is increasingly important as use of the LNG-IUS grows to include women at higher risk for STIs. This study assessed the impact of the LNG-IUS on development of Chlamydia trachomatis pelvic inflammatory disease, using a baboon model. Methods: Baboons with and those without the LNG-IUS were cervically inoculated with C. trachomatis and monitored daily, and cervical and fallopian tube swab specimens were collected weekly for C. trachomatis quantitation by nucleic acid amplification testing and culture. Vaginal swab specimens were collected for cytokine analysis, and serum samples were obtained for detection of C. trachomatis antibodies. Results: The LNG-IUS resulted in an increased C. trachomatis burden in the cervix, with the bacterial burden in the LNG-IUS group diverging from that in the non-LNG-IUS group by 6 weeks after infection. One of 7 baboons in the non-LNG-IUS group and 2 of 6 in the LNG-IUS group developed pelvic inflammatory disease, while 3 animals in each group met criteria suggestive of pelvic inflammatory disease. LNG-IUS increased baseline interleukin 8 levels but failed to further upregulate interleukin 8 during infection. In LNG-IUS recipients, early perturbations in the interleukin 1ß axis corresponded to decreased C. trachomatis clearance and increased T-helper type 2 immune responses. Conclusion: LNG-IUS use results in delayed clearance of C. trachomatis and might alter the reproductive tract immune environment.

Anti-inflammatory Effects of the Natural Compounds Cortex Phellodendri and Humulus japonicus on Pelvic Inflammatory Disease in Mice.

Pelvic inflammatory disease (PID) is an inflammatory and/or infectious disorder of the upper female genital tract, including the uterus, fallopian tubes, and adjacent pelvic structures, that may spread upward to the peritoneum. Currently available treatment options have presented to produce adverse effects of various degrees, such as increased antimicrobial resistance and a limited effective duration of hormones. In the study, the Cortex Phellodendri (CP) and Humulus japonicus (HJ) among natural compounds that are believed to present biological activities with fewer side effects were tested in a PID animal model. The results suggested that the administration CP and HJ reduced clinical signs, inflammatory cytokine expression as well as secretion in uterine tissue, and neutrophil infiltration into the tissue.

Anti-inflammatory effect of Man-Pen-Fang, a Chinese herbal compound, on chronic pelvic inflammation in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM) has become the focus of research for the treatment of chronic pelvic inflammatory disease (CPID) based on unique medical theory system. Man-Pen-Fang (MPF), a Chinese herbal compound, which is composed of Thlaspi arvense L. (Cruciferae), Gleditsia sinensis Lam. (Leguminosae), Smilax china L. (Liliaceae), Euonymus alatus (Thunb.) Sieb. (Celastraceae) and Vaccaria segetalis (Neck.) (Caryophyllaceae) MPF has been used for the treatment of CPID and exerted significant clinical curative effects. However, the corresponding active principles and anti-inflammatory mechanism of MPF are still unknown. AIM OF THE STUDY: The objective of present study is to evaluate the effect of MPF on CPID in the chronic pelvic inflammation (CPI) rat model and elucidate its possible anti-inflammatory mechanism. MATERIALS AND METHODS: The CPI in rats was induced by administration with E. coli, Staphylococcus aureus and Beta-hemolytic streptococcus. MPF (8.112g/(kg d) (20 times of adult dosage), 4.056g/(kg d) (10 times of adult dosage) and 2.028g/(kg d) (5 times of adult dosage)) and Jingangteng Capsule 2g/(kg d) (20 times of adult dosage) were administered orally for 20 days. The serum levels of five inflammation-associated cytokines (IL-2, IL-6, IL-10, TNF-α and TGF-ß1) were determined by enzyme-linked immunoassay, and the mRNA expression levels of TGF-ß1, P53, Fas, FasL and MMP-2 in the uterus tissue were measured by quantitative RT-PCR. Furthermore, the expression of NF-κB p65 in uterus and ovary tissues was detected by immunohistochemistry assay and the pathological changes induced in the uterus and ovary tissues were observed by histology. RESULTS: MPF caused a reduction in serum levels of IL-2, IL-6, IL-10, TNF-α and TGF-ß1. The expression of P53 mRNA, Fas/FasL mRNA and MMP-2 mRNA in the uterus tissue was significantly elevated after treating with MPF, in contrast the expression of TGF-ß1 mRNA was decreased. Furthermore, the expression of NF-κB p65 in uterus and ovary tissue was inhibited after treating with MPF. CONCLUSIONS: These results taken together suggest that MPF has a significant anti-CPID effect, probably due to inhibition of the inflammation reaction by the promotion, and the induction of the apoptosis of inflammatory cells and downregulation of the serum levels of inflammation cytokines.

Enterobius vermicularis in tubo-ovarian abscess: A rare and interesting incidental finding - A case Report.

Enterobius vermicularis is a common intestinal nematode; however, rare extraintestinal Enterobius infections have been reported from different parts of the world. Here, we present a case of tubo-ovarian abscess in an otherwise healthy young sexually active female with no known comorbids with history of on and off lower abdominal pain for one year and high grade fever for one month. On the basis of further workup and radiological evaluation, a preoperative diagnosis of right sided tubo-ovarian abscess was made and salpingo-oophorectomy was performed laproscopically in July 2015. Histopathology of the resected tissue revealed necrosis and in one area Enterobius vermicularis was identified surrounded by neutrophils and eosinophil rich abscess. A final diagnosis of severe acute and chronic salpingo-oophoritis with abscess formation, secondary to Enterobius vermicularis was made. Signs and symptoms of parasitic involvement in tubo-ovarian abscesses are not much different than usual presentations of pelvic inflammatory diseases and identification of a parasite in a tubo-ovarian tissue sample is a rare clinical finding. A high index of suspicion on the part of histopathologist as well as clinician is important for timely diagnosis and effective management of such cases.

Is Pelvic Inflammatory Disease a Risk Factor for Ovarian Cancer?

BACKGROUND: Pelvic inflammatory disease (PID) has been proposed as a risk factor for ovarian cancer. However, the existing literature on the association between PID and ovarian cancer risk is inconclusive, and only few cohort studies have been conducted. METHODS: Using nationwide Danish registries, we conducted a population-based cohort study including all women from the birth cohorts 1940 to 1970 in Denmark during 1978-2012 (n = 1,318,929) to investigate the association between PID and subsequent risk of epithelial ovarian cancer. Among women in the cohort, 81,281 women were diagnosed with PID and 5,356 women developed ovarian cancer during follow-up through 2012. Cox regression models were used to estimate HRs and 95% confidence intervals (CI) for the association between PID and ovarian cancer, both overall and according to histotype. RESULTS: For ovarian cancer overall, we observed no association with PID (HR, 1.05; 95% CI, 0.92-1.20). However, in histotype-specific analyses, we found a statistically significantly increased risk of serous ovarian cancer among women with PID (HR, 1.19; 1.00-1.41; P = 0.047). Conversely, PID was not convincingly associated with risk of any of the other histotypes of ovarian cancer. CONCLUSIONS: PID was associated with a modestly increased risk of serous ovarian cancer, but not other histotypes. IMPACT: Our results indicate that PID is not a strong risk factor for ovarian cancer. Whether PID is slightly associated with risk of serous ovarian cancer has to be confirmed in other studies. Cancer Epidemiol Biomarkers Prev; 26(1); 104-9. ©2016 AACR.