Efficacy of carboxymethyl beta-glucan in cervical intraepithelial neoplasia: a retrospective, case-control study.

BACKGROUND: Persistent human papillomavirus (HPV) infection constitutes the principal risk factor for the development of cervical intraepithelial neoplasia (CIN) and cervical cancer. For this reason, new drugs have been studied to support the host immune system against the HPV infection. The aim of this retrospective, case-control study was to detect the efficacy and safety of carboxymethyl ß-glucan (Colpofix®) gel as adjuvant therapy in HPV infection. METHODS: The medical records of patients attending the Colposcopy Service of four hospitals in Rome from 2011 to 2013 were collected. Case arm consisted of patients submitted to local therapy with Colpofix®. Control arm comprised patients who did not receive this therapy. A total of 999 patients were included, divided into four groups, according to their cytological and histological specimens, colposcopy and subsequent management. RESULTS: Local therapy with Colpofix® gel resulted effective with respect to no therapy for the regression of low-grade CIN (CIN1) in patients submitted to follow up (P=0.0204), while it was no effective for the regression of CIN1 submitted to ablative therapy and high-grade CIN (CIN 2+) (P value not significant). CONCLUSIONS: In conclusion, Colpofix® gel represents a valid alternative to "wait and see" strategy in patients affected by CIN1. Further prospective studies are warranted to confirm these results.

TLR9 is expressed in human papillomavirus-positive cervical cells and is overexpressed in persistent infections.

Control of human papillomavirus (HPV) infection involves the activation of Toll-like receptors (TLRs), key components of the mucosal antiviral response. Available studies on TLR expression in HPV-positive cervical cells are limited and reported conflicting results. This study quantified TLR 2, 3, 4, 7 and 9 transcripts in low-risk (LR) and high-risk (HR) HPV-positive and HPV-negative cervical samples from 154 women attending a gynaecological clinic. Expression levels of TLR 2, 3, 4 and 7 did not differ among samples, whereas TLR9 levels were quite significantly higher in LR and marginally significant in HR HPV-positive samples, with respect to the HPV-negative samples. Interestingly, in a subgroup of women with documented previous HPV-infection, TLR9 levels were extremely higher in patients persistently positive to the same HPV genotype for more than 1 year, with respect to women who cleared HPV infection and to those re-infected with a different genotype. These findings implicate TLR9 in the response to LR and HR HPVs, including HPV 16 known to interfere with TLR9 transcription in cell lines. Elevated TLR9 levels without HPV clearance in persistently infected women could drive inflammation thereby contributing to cervical cancer risk.

Interferon lambda 1 expression in cervical cells differs between low-risk and high-risk human papillomavirus-positive women.

Persistent infection by high-risk (HR) human papillomavirus (HPV) types is a prerequisite for progression to cancer. HR-HPVs may lead to a deregulation of innate immunity by interfering with the epithelial type I interferon (IFN) response, whereas very little is known about type III IFNs, a key component of the mucosal antiviral response. This study reports a first attempt to evaluate the activation of type III IFN genes (IFN lambda 1-3), IFN lambda receptor genes (IFN-lambdaR1 and IL10R2), and IFN-induced genes (MxA, ISG15, ISG56) in HPV-positive and HPV-negative cervical cells from 154 women attending the gynecological unit of a university hospital in Rome. Despite an increased individual variability, a coordinated expression of several IFN lambda-related genes was observed. Furthermore, IFN lambda 1 and IFN-lambdaR1 genes were expressed at higher levels in cervical cells positive to low-risk (LR) HPV compared to HR-HPV and HPV-negative cells. Consistently, ISG15 expression was significantly higher in LR-HPV-infected women than in the other groups. Moreover, IFN lambda 1 expression decreased significantly with abnormal cytological results. This study is the first to show the activation of a type III IFN response in LR-HPV-positive cervical cells and suggests that the lack of this response in HR-HPV infection may be related to lesion progression.

Lack of association between genetic variants in the mannose-binding lectin 2 (MBL2) gene and HPV infection.

Genetic variants in the immunomodulatory gene mannose-binding lectin 2 (MBL2), were associated with risk, severity, and frequency of viral infections. In a case-control setting, we investigated the association of MBL2 functional polymorphisms with Human Papillomas Virus (HPV) infection. No differences between cases (HPV(+)) and controls (HPV(-)) were found in the distribution of each single genotypes or allele. Haplotype analysis did not show any difference between HPV+ and HPV(-) groups.

Young women, cervical intraepithelial neoplasia and human papillomavirus: risk factors for persistence and recurrence.

Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections (STIs) in young women. They can occur in one or multiple areas of the female genitalia. Usually, the vulva is the initial site of implantation for HPV. The purpose of our study is to evaluate the epidemiological aspects, incidence of single or multiple lesions in the lower genital tract, correlation between sexual behaviour and their localization and behaviour risk factors for persistence and recurrence of HPV lesions and cervical intraepithelial lesion (CIN) in a long-term follow-up among young women. We recruited 268 patients aged 11-21 years who previously had cytology and/or physical examination suspicious for HPV infection. The women were interviewed and asked information about lifestyle, sexual behaviour, work, personal or family history of genital warts and school attendance. We considered individuals to be 'smokers' if they smoked more than five cigarettes/day. No specific data were recorded about oral contraception, nevertheless, no woman had used oral contraceptives (OCs) for more than 2 years. Young women included in the study were between the age of 12 and 21 years who had HVP lesions after entry examinations and had undergone no treatment for HPV lesions prior to entry. Other exclusion criteria relevant to this study included cervical excisional treatment prior to entry or later. Two hundred and thirty-four young women were included in our study group. Our diagnostic schedule for a complete evaluation included exo- and endocervical cytology, colposcopy, directed biopsy and microcolpohysteroscopy. The treatment was performed with a LASER CO2 Coherent 400, model 451, with Zeiss photocolposcopy attachment. The finding that, among 126/234 (53.8%) adolescents using contraceptives, only 85 (36.3%) have used condom, the only barrier form of contraceptive effectively protecting against virus, shows a low awareness of the high risk for contracting HPV infection among young sexually active women. The sites most frequently affected in our study were vulva, perianus and perineum (194/234), 82.9% and the cervix (125/234), 53.4%. Vaginal lesions were detected only in 29/234 patients (12.3%). According to our data, in 161 patients, sexual habits, age at the first intercourse (P=0.68), frequency of intercourses (P=0.49) and number of lifetime partners (P=0.27) as well as age (P=0.26) play a role in transmission and incidence of HPV infection but not on the location of the lesions. This can be due to a coexistent clinical and subclinical multiple infection as well as a transmission via intercourse or from other sources, including tampons. Abnormal Pap test was related to HPV infection, but the low correlation with colposcopic and histological findings in this study justify the support of other examinations such as colposcopy and punch biopsy for diagnosis. Moreover, according to our data, cytology alone shows to be not suitable to exclude CIN (seven underestimated cases of CIN) and a closer correspondence were found between colposcopy and the result of histological sample after punch biopsy in CIN detection. More attention must be paid to psychological aspect of diagnoses and treatment among adolescents, more than older women as the high rate of patients lost shows in our study: 75/234 (32.05%) before LASER surgery and 55/159 (34.59%) during follow-up. International data shows that only 12-45% of sexually active adolescent girls have obtained Pap smear screening. In our study, we found no correlation between treatment failure and cigarette smoking or between the use of oral contraceptives and persistence/recurrence after LASER CO2 surgery. Because the small sample of our study group, further analyses were required.

Human papillomavirus in virgins and behaviour at risk.

Human papillomavirus (HPV) infection is one of the most common sexual transmitted diseases (STDs). We compared two groups of virgins with genital HPV lesions to evaluate the behaviour at risk in the transmission of HPV infection. Partners were also examined. HPV lesions were detected in 88 virgins, who have never had sexual intercourse. This can be due to vertical transmission, fomities and skin-to-skin contact. Many other hypothesis can be proposed to explain HPV genital infection, however, further studies are required.

Giant condyloma acuminatum or buschke-Lowenstein tumor: review of the literature and report of three cases treated by CO2 laser surgery. A long-term follow-up.

Giant condyloma acuminatum or Buschke-Lowenstein tumor (TBL) is a rare disease that arises on the male and female external genitalia. TBL arises from the confluence of multiple condylomata acuminata and it is induced a Human Papillomavirus infection. TBL presents a clinical malignancy, but it is known to be a histologically benign tumor, even if it carries a risk of malignant transformation. It is advisable to treat it early. After a review of the literature, three cases of giant condyloma acuminatum, treated by combined CO2 Laser surgery excision-vaporization and which underwent a long-term follow-up are described.