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Diagnosis of Lower Genital Tract Disease

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A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 23384

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Special Issue Editors

Dr. Fabio Bottari

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Guest Editor

Division of Laboratory Medicine, European Istitute of Oncology, Via Ripamonti, 435, 20141 Milan, Italy
Interests: laboratory medicine; molecular biology; HPV; tumor biology; diagnostics tool

Dr. Anna Daniela Iacobone

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Guest Editor

Preventive Gynecology Unit, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
Interests: gynecologic oncology; lower genital tract disease; HPV; colposcopy; ultrasound
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lower genital tract diseases include vulvovaginal and HPV-related diseases, ranging from benign to pre-neoplastic and neoplastic lesions. Nowadays, increasing interest is focused on innovative methods to diagnose and prevent cervical cancer through HPV primary screening programs. However, other lower genital tract diseases are not related to HPV infection, hence cytology, colposcopy and sonography might play a crucial role in assessment and management. This Special Issue aims to address current and emerging issues in the field of the diagnosis, assessment, staging and management of HPV-related and not-related pathology of the lower female ano-genital tract. These may include new advancements in HPV testing and laboratory biomarkers, investigations on the actual role of cytology and implementation of diagnostic tools to implement differential diagnosis, and the current clinical management of lower genital tract diseases.

Dr. Fabio Bottari
Dr. Anna Daniela Iacobone
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

HPV
cervical cancer screening
vulvo-vaginal disease
colposcopy
sonography
HPV testing
cytology

Published Papers (12 papers)

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3 pages, 171 KiB

Open AccessEditorial

The Editorial of the Special Issue “Diagnosis of Lower Genital Tract Disease”

by Fabio Bottari and Anna Daniela Iacobone

Diagnostics 2023, 13(15), 2515; https://doi.org/10.3390/diagnostics13152515 - 28 Jul 2023

Viewed by 705

Abstract

A range of conditions involving the vulvovaginal and anal area, and those associated with human papillomavirus (HPV) infection, which can manifest as benign, pre-neoplastic, or neoplastic lesions, can be grouped into lower genital tract diseases [...] Full article

(This article belongs to the Special Issue Diagnosis of Lower Genital Tract Disease)

Research

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14 pages, 2285 KiB

Open AccessArticle

Colposcopy Accuracy and Diagnostic Performance: A Quality Control and Quality Assurance Survey in Italian Tertiary-Level Teaching and Academic Institutions—The Italian Society of Colposcopy and Cervico-Vaginal Pathology (SICPCV)

by Massimo Origoni, Francesco Cantatore, Francesco Sopracordevole, Nicolò Clemente, Arsenio Spinillo, Barbara Gardella, Rosa De Vincenzo, Caterina Ricci, Fabio Landoni, Maria Letizia Di Meo, Andrea Ciavattini, Jacopo Di Giuseppe, Eleonora Preti, Anna Daniela Iacobone, Carmine Carriero, Miriam Dellino, Massimo Capodanno, Antonino Perino, Cesare Miglioli, Luca Insolia, Maggiorino Barbero and Massimo Candiani Show full author list Hide full author list

Diagnostics 2023, 13(11), 1906; https://doi.org/10.3390/diagnostics13111906 - 29 May 2023

Cited by 4 | Viewed by 2124

Abstract

Quality Control (QC) and Quality Assurance (QA) principles are essential for effective cervical cancer prevention. Being a crucial diagnostic step, colposcopy’s sensitivity and specificity improvements are strongly advocated worldwide since inter- and intra-observer differences are the main limiting factors. The objective of the present study was the evaluation of colposcopy accuracy through the results of a QC/QA assessment from a survey in Italian tertiary-level academic and teaching hospitals. A web-based, user-friendly platform based on 100 colposcopic digital images was forwarded to colposcopists with different levels of experience. Seventy-three participants were asked to identify colposcopic patterns, provide personal impressions, and indicate the correct clinical practice. The data were correlated with a panel of experts’ evaluation and with the clinical/pathological data of the cases. Overall sensitivity and specificity with the threshold of CIN2+ accounted for 73.7% and 87.7%, respectively, with minor differences between senior and junior candidates. Identification and interpretation of colposcopic patterns showed full agreement with the experts’ panel, ranging from 50% to 82%, in some instances with better results from junior colposcopists. Colposcopic impressions correlated with a 20% underestimation of CIN2+ lesions, with no differences linked to level of experience. Our results demonstrate the good diagnostic performance of colposcopy and the need for improving accuracy through QC assessments and adhesion to standard requirements and recommendations. Full article

(This article belongs to the Special Issue Diagnosis of Lower Genital Tract Disease)

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22 pages, 1845 KiB

Open AccessArticle

E6/E7 mRNA Expression of the Most Prevalent High-Risk HPV Genotypes in Cervical Samples from Serbian Women

by Natasa Nikolic, Branka Basica, Aljosa Mandic, Nela Surla, Vera Gusman, Deana Medic, Tamas Petrovic, Mirjana Strbac and Vladimir Petrovic

Diagnostics 2023, 13(5), 917; https://doi.org/10.3390/diagnostics13050917 - 28 Feb 2023

Cited by 5 | Viewed by 2966

Abstract

Cervical cancer caused by persistent infection with HR HPV genotypes is the second leading cause of death in women aged 15 to 44 in Serbia. The expression of the E6 and E7 HPV oncogenes is considered as a promising biomarker in diagnosing high-grade squamous intraepithelial lesions (HSIL). This study aimed to evaluate HPV mRNA and DNA tests, compare the results according to the severity of the lesions, and assess the predictive potential for the diagnosis of HSIL. Cervical specimens were obtained at the Department of Gynecology, Community Health Centre Novi Sad, Serbia, and the Oncology Institute of Vojvodina, Serbia, during 2017–2021. The 365 samples were collected using the ThinPrep Pap test. The cytology slides were evaluated according to the Bethesda 2014 System. Using a real-time PCR test, HPV DNA was detected and genotyped, while the RT-PCR proved the presence of E6 and E7 mRNA. The most common genotypes in Serbian women are HPV 16, 31, 33, and 51. Oncogenic activity was demonstrated in 67% of HPV-positive women. A comparison of the HPV DNA and mRNA tests to assess the progression of cervical intraepithelial lesions indicated that higher specificity (89.1%) and positive predictive value (69.8–78.7%) were expressed by the E6/E7 mRNA test, while higher sensitivity was recorded when using the HPV DNA test (67.6–88%). The results determine the higher probability of detecting HPV infection by 7% provided by the mRNA test. The detected E6/E7 mRNA HR HPVs have a predictive potential in assessing the diagnosis of HSIL. The oncogenic activity of HPV 16 and age were the risk factors with the strongest predictive values for the development of HSIL. Full article

(This article belongs to the Special Issue Diagnosis of Lower Genital Tract Disease)

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12 pages, 2294 KiB

Open AccessArticle

Tips and Tricks for Early Diagnosis of Cervico-Vaginal Involvement from Extramammary Paget’s Disease of the Vulva: A Referral Center Experience

by Anna Daniela Iacobone, Maria Elena Guerrieri, Eleonora Petra Preti, Noemi Spolti, Gianluigi Radici, Giulia Peveri, Vincenzo Bagnardi, Giulio Tosti, Angelo Maggioni, Fabio Bottari, Chiara Scacchi and Mariacristina Ghioni

Diagnostics 2023, 13(3), 464; https://doi.org/10.3390/diagnostics13030464 - 27 Jan 2023

Cited by 1 | Viewed by 1340

Abstract

Cervico-vaginal (CV) localization of extra-mammary Paget’s disease (EMPD) of the vulva is extremely rare. In order to investigate the incidence risk and the pathognomonic clinical and pathological features of this condition, a retrospective analysis was conducted including 94 women treated for vulvar EMPD at the European Institute of Oncology, Milan, Italy, from October 1997 to May 2020. Overall nine patients developed CV involvement from EMPD, with a cumulative incidence of 2.5% (95% CI: 0.5–8.0%) at 5 years, 6.5% (95% CI: 1.9–15.1%) at 10 years and 14.0% (95% CI: 4.8–27.8%) at 15 years, respectively. All cases except one were firstly detected by abnormal glandular cytology. None reported vaginal bleeding or other suspicious symptoms. The colposcopic findings were heterogeneous and could sometimes be misdiagnosed. Cervical and/or vaginal biopsies were always performed for histopathological diagnosis by identification of Paget cells in the epithelium or stroma. Most patients developed invasive EMPD (5/9) of the cervix and/or vagina and underwent hysterectomy with partial or total colpectomy. CV involvement from EMPD should not be underestimated in women with a long-standing history of vulvar Paget’s disease. Liquid-based cytology with immunocytochemistry represents a valuable tool for early diagnosis and should be routinely performed during the required lifelong follow-up. Full article

(This article belongs to the Special Issue Diagnosis of Lower Genital Tract Disease)

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14 pages, 1769 KiB

Open AccessArticle

Which Risk Factors and Colposcopic Patterns Are Predictive for High-Grade VAIN? A Retrospective Analysis

by Anna Daniela Iacobone, Davide Radice, Maria Elena Guerrieri, Noemi Spolti, Barbara Grossi, Fabio Bottari, Sara Boveri, Silvia Martella, Ailyn Mariela Vidal Urbinati, Ida Pino, Dorella Franchi and Eleonora Petra Preti

Diagnostics 2023, 13(2), 176; https://doi.org/10.3390/diagnostics13020176 - 04 Jan 2023

Cited by 2 | Viewed by 2619

Abstract

Colposcopic patterns of Vaginal Intraepithelial Neoplasia (VAIN) are not definitively related to histological grade. The aim of the present study was to investigate any correlation between clinical and colposcopic features and the development of high-grade VAIN. Two hundred and fifty-five women diagnosed with VAIN (52 VAIN1, 55 VAIN2 and 148 VAIN3) at the European Institute of Oncology, Milan, Italy, from January 2000 to June 2022, were selected for a retrospective analysis. Multivariate logistic regression was performed to estimate the association of risk factors and colposcopic patterns with VAIN grade. Smoking was associated with the development of VAIN (34.1%, p = 0.01). Most women diagnosed with VAIN3 (45.3%, p = 0.02) had a previous history of hysterectomy for CIN2+. At multivariate analysis, colposcopic grade G2 (OR = 20.4, 95%CI: 6.67–61.4, p < 0.001), papillary lesion (OR = 4.33, 95%CI: 1.79–10.5, p = 0.001) and vascularity (OR = 14.4, 95%CI: 1.86–112, p = 0.01) were significantly associated with a greater risk of VAIN3. The risk of high-grade VAIN should not be underestimated in women with a history of smoking and previous hysterectomy for CIN2+, especially when colposcopic findings reveal vaginal lesions characterized by grade 2, papillary and vascular patterns. Accurate diagnosis is crucial for an optimal personalized management, based on risk factors, colposcopic patterns and histologic grade of VAIN. Full article

(This article belongs to the Special Issue Diagnosis of Lower Genital Tract Disease)

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12 pages, 728 KiB

Open AccessArticle

Mapping HPV 16 Sub-Lineages in Anal Cancer and Implications for Disease Outcomes

by Daniel Guerendiain, Laila Sara Arroyo Mühr, Raluca Grigorescu, Matthew T. G. Holden and Kate Cuschieri

Diagnostics 2022, 12(12), 3222; https://doi.org/10.3390/diagnostics12123222 - 19 Dec 2022

Cited by 2 | Viewed by 1706

Abstract

The incidence of anal cancer is rising worldwide. As identified in cervical cancer management, an improvement in the early detection and management of anal pre-cancer is essential. In other cancers associated with human papillomavirus (HPV), HPV 16 sub-lineages have been shown to be associated with disease status and prognosis. However, in anal cancer, they have been under-explored. A total of 119 HPV 16-positive anal cancer lesions diagnosed between 2009 and 2018 in Scotland and 134 HPV 16-positive residual rectal swabs from asymptomatic men collected in 2016/7 were whole genome sequenced. The association of HPV 16 sub-lineages with underlying disease status (cancer vs. asymptomatic) and overall survival in anal cancer samples was assessed (comparing A1 vs non-A1 sub-lineages). A1 was the dominant sub-lineage present in the anal cancer (76.5%) and the asymptomatic (76.1%) cohorts. A2 was the second most dominant sub-lineage in both groups (16.8% and 17.2%, respectively). We did not observe significant associations of sub-lineage with demographics, clinical variables or survival (A1 vs. non-A1 sub-lineages (HR 0.83, 0.28–2.46 p = 0.743)). HPV 16 sub-lineages do to not appear to cluster with disease vs asymptomatic carriage or be independently associated with outcomes in anal cancer patients. Further international studies on anal HPV sub-lineage mapping will help to determine whether this is a consistent observation. Full article

(This article belongs to the Special Issue Diagnosis of Lower Genital Tract Disease)

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11 pages, 1900 KiB

Open AccessArticle

Evaluation of BD Onclarity™ HPV Assay on Self-Collected Vaginal and First-Void Urine Samples as Compared to Clinician-Collected Cervical Samples: A Pilot Study

by Marianna Martinelli, Chiara Giubbi, Illari Sechi, Fabio Bottari, Anna Daniela Iacobone, Rosario Musumeci, Federica Perdoni, Narcisa Muresu, Andrea Piana, Robert Fruscio, Fabio Landoni and Clementina Elvezia Cocuzza

Diagnostics 2022, 12(12), 3075; https://doi.org/10.3390/diagnostics12123075 - 07 Dec 2022

Cited by 4 | Viewed by 1465

Abstract

The accuracy of available HPV molecular assays on self-samples needs to be evaluated as compared to clinician-collected samples. This pilot study aimed to investigate the BD Onclarity™ HPV assay on vaginal and first-void urine samples. Sixty-four women referred to colposcopy for cervical dysplasia performed a vaginal self-collection and provided a first-void urine sample, after informed consent. A cervical specimen was collected during the clinician examination. All samples were tested using BD Onclarity™ HPV assay on the BD Viper™ LT System. Overall positive agreement (OPA) between cervical and self-sample results was evaluated using Cohen’s kappa value (κ). Using a clinical cut-off of 38.3 Ct for HPV 16 and 34.2 Ct for other HR genotypes, compared to cervical sample, the self-collected vaginal sample OPA was 85.9%, and κ = 0.699. Without a clinical cut-off, the OPA was 95.3%, and the κ = 0.890. Data obtained comparing cervical and urine samples showed an OPA of 87.5% with a κ = 0.79 using a clinical cut-off, and an OPA of 90.6% with a κ = 0.776 without a clinical cut-off. Data showed a substantial agreement between both self-collected and clinician-collected samples. A specific clinical cut-off analysis should be considered based on type of sample analysed. Full article

(This article belongs to the Special Issue Diagnosis of Lower Genital Tract Disease)

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12 pages, 2953 KiB

Open AccessArticle

Clinical, Sonographic, and Hysteroscopic Features of Endometrial Carcinoma Diagnosed after Hysterectomy in Patients with a Preoperative Diagnosis of Atypical Hyperplasia: A Single-Center Retrospective Study

by Luca Pace, Silvia Actis, Matteo Mancarella, Lorenzo Novara, Luca Mariani, Gaetano Perrini, Francesca Govone, Alessandra Testi, Paola Campisi, Annamaria Ferrero and Nicoletta Biglia

Diagnostics 2022, 12(12), 3029; https://doi.org/10.3390/diagnostics12123029 - 02 Dec 2022

Cited by 1 | Viewed by 1858

Abstract

Background: atypical endometrial hyperplasia (AEH) is a precancerous condition implying a high risk of concurrent endometrial cancer (EC), which might be occult and only diagnosed at postoperative histopathological examination after hysterectomy. Our study aimed to investigate potential differences in preoperative clinical, sonographic, and hysteroscopic characteristics in patients with AEH and postoperative diagnosis of EC. Methods: a retrospective single-center study was carried out on a case series of 80 women with AEH undergoing diagnostic workup, including ultrasonography and hysteroscopy, with subsequent hysterectomy. Women with AEH confirmed at the histopathological examination were compared with patients with a postoperative diagnosis of EC. Results: in our population, EC was diagnosed in 53 women, whereas the preoperative diagnosis of AEH was confirmed in 27 cases. At ultrasonography, women with occult EC showed greater endometrial thickness (20.3 mm vs. 10.3 mm, p 0.001) and size of the endocavitary lesion (maximum diameter 25.2 mm vs. 10.6 mm, p 0.001), and a higher prevalence of irregular endometrial-myometrial junction (40.5% vs. 6.7%, p 0.022) and endouterine vascularization at color Doppler (64.2% vs. 34.6%, p 0.017). At hysteroscopy, patients with occult EC showed a higher prevalence of necrosis (44.2% vs. 4.2%, p 0.001) and atypical vessels (70.6% vs. 33.3%, p 0.003), whereas true AEH mainly presented as a protruding intracavitary lesion (77.8% vs. 50.9%, p 0.029). In EC, subjective assessment by the operator was more frequently indicative of cancer (80.0% vs. 12.5%). No difference was found for clinical variables. Conclusions: occult EC in AEH may exhibit some differences in ultrasonographic and hysteroscopic patterns of presentation compared with real AEH, which could prompt a more significant suspect for the possible presence of concurrent EC at preoperative diagnostic workup. Full article

(This article belongs to the Special Issue Diagnosis of Lower Genital Tract Disease)

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11 pages, 2072 KiB

Open AccessArticle

Vaginosonography versus MRI in Pre-Treatment Evaluation of Early-Stage Cervical Cancer: An Old Tool for a New Precision Approach?

by Ailyn M. Vidal Urbinati, Ida Pino, Anna D. Iacobone, Davide Radice, Giulia Azzalini, Maria E. Guerrieri, Eleonora P. Preti, Silvia Martella and Dorella Franchi

Diagnostics 2022, 12(12), 2904; https://doi.org/10.3390/diagnostics12122904 - 22 Nov 2022

Cited by 1 | Viewed by 1203

Abstract

This study aims to analyze the sensitivity of vaginosonography (VGS) and magnetic resonance imaging (MRI) in the preoperative local evaluation of early-stage cervical cancers and to assess their accuracy in the detection of tumors, size of the lesions and stromal invasion by comparing them with the final histopathology report. This single-center study included 56 consecutive patients with cervical cancer who underwent VGS and MRI from November 2012 to January 2021. VGS significantly overestimated the lesion size by 2.7 mm (p = 0.002), and MRI underestimated it by 1.9 mm (p = 0.11). Both MRI and VGS had a good concordance with the pathology report (Cohen’s kappa of 0.73 and 0.81, respectively). However, MRI had a false-negative rate (38.1%) that was greater than VGS (0%) in cases of cervical tumor size <2 cm. We found a good concordance between histology and VGS in the stromal infiltration assessment, with 89% sensitivity (95% CI 0.44–0.83) and 89% specificity (95% CI 0.52–0.86). VGS is a simple, inexpensive, widely available, and fast execution method that can complement ultrasound in particular cases and show a good correlation with MRI in the assessment of tumor dimensions, with a better performance in detecting small tumors (<2 cm). Full article

(This article belongs to the Special Issue Diagnosis of Lower Genital Tract Disease)

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9 pages, 719 KiB

Open AccessArticle

HPV Tests Comparison in the Detection and Follow-Up after Surgical Treatment of CIN2+ Lesions

by Fabio Bottari, Anna Daniela Iacobone, Davide Radice, Eleonora Petra Preti, Mario Preti, Dorella Franchi, Sara Boveri, Maria Teresa Sandri and Rita Passerini

Diagnostics 2022, 12(10), 2359; https://doi.org/10.3390/diagnostics12102359 - 29 Sep 2022

Cited by 5 | Viewed by 1897

Abstract

Background: HPV tests differ for technology, targets, and information on genotyping of high risk (HR) HPV. In this study, we evaluated the performance of 6 HPV DNA tests and one mRNA test in the detection of cervical intraepithelial lesions (CIN) and as a test-of-cure in the follow-up after surgical conservative treatment. Methods: One hundred seventy-two women referred to the European Institute of Oncology, Milan, for surgical treatment of pre-neoplastic cervical lesions, were enrolled in this study (IEO S544) from January 2011 to June 2015. For all women, a cervical sample was taken before treatment (baseline) and at the first follow-up visit (range 3 to 9 months): on these samples Qiagen Hybrid Capture 2 (HC2), Roche Linear Array HPV Test (Linear Array), Roche Cobas 4800 HPV test (Cobas), Abbott RealTime High Risk HPV test (RT), BD Onclarity HPV assay (Onclarity), Seegene Anyplex II HPV HR Detection (Anyplex), and Hologic Aptima HPV Assay (Aptima) histology and cytology were performed at baseline, and the same tests and cytology were performed at follow-up. Results: At baseline 158/172 (92%), histologies were CIN2+, and 150/172 (87%) women were recruited at follow-up. Assuming HC2 as a comparator, the concordance of HPV tests ranges from 91% to 95% at baseline and from 76% to 100% at follow-up (PABAK ranging from 0.81 to 0.90 at baseline and PABAK ranging from 0.53 to 1 at follow-up). All HPV showed a very good sensitivity in CIN2+ detection at baseline, more than 92%, and a very good specificity at follow-up, more than 89%. Conclusions: HPV tests showed a good concordance with HC2 and a very good and comparable sensitivity in CIN2+ detection. Hence, an HPV test represents a valid option as test-of-cure in order to monitor patients treated for CIN2+ lesions during follow-up. Full article

(This article belongs to the Special Issue Diagnosis of Lower Genital Tract Disease)

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8 pages, 2057 KiB

Open AccessArticle

“Modified Schirmer Test” as an Objective Measurement for Vaginal Dryness: A Prospective Cohort Study

by Dana Gabrieli, Yael Suissa-Cohen, Sireen Jaber and Ahinoam Lev-Sagie

Diagnostics 2022, 12(3), 574; https://doi.org/10.3390/diagnostics12030574 - 23 Feb 2022

Cited by 2 | Viewed by 1767

Abstract

None of the currently available parameters allow for a direct and objective measurement of vaginal moisture. We used a calibrated filter paper strip as a measurement tool for the quantification of vaginal fluid, in a similar manner as the ophthalmic “Schirmer test” (used for eye moisture measurement). The study aimed to evaluate the validity of this new, objective tool, to measure vaginal moisture. We compared vaginal moisture measurements using the “modified Schirmer test” in symptomatic women with genitourinary syndrome of menopause to those of women without vaginal dryness. The mean “modified Schirmer test” measurement in the control group was 21.7 mm compared to 3.3 mm in the study group, yielding a statistically significant difference (p < 0.001). Strong correlations were found between “modified Schirmer test” measurements and pH (correlation coefficient −0.714), Vaginal Health Index [VHI (0.775)], and Visual Analogue Score (VAS) of dryness during intercourse (−0.821). Our findings suggest that the “modified Schirmer test” can be used as an objective measurement for the assessment of vaginal fluid level. This test may also prove useful for evaluation of non-hormonal treatments aimed to treat vaginal dryness. Full article

(This article belongs to the Special Issue Diagnosis of Lower Genital Tract Disease)

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17 pages, 1449 KiB

Open AccessSystematic Review

Prevalence of Human Papilloma Virus Infection in Bladder Cancer: A Systematic Review

by Narcisa Muresu, Biagio Di Lorenzo, Laura Saderi, Illari Sechi, Arcadia Del Rio, Andrea Piana and Giovanni Sotgiu

Diagnostics 2022, 12(7), 1759; https://doi.org/10.3390/diagnostics12071759 - 20 Jul 2022

Cited by 9 | Viewed by 2059

Abstract

The etiology of bladder cancer is known to be associated with behavioral and environmental factors. Moreover, several studies suggested a potential role of HPV infection in the pathogenesis with controversial results. A systematic review was conducted to assess the role of HPV. A total of 46 articles that reported the prevalence of HPV infection in squamous (SCC), urothelial (UC), and transitional cell carcinomas (TCC) were selected. A pooled prevalence of 19% was found, with a significant difference in SCC that was mainly driven by HPV-16. Moreover, infection prevalence in case-control studies showed a higher risk of bladder cancer in HPV-positive cases (OR: 7.84; p-value < 0.00001). The results may suggest an etiologic role of HPV in bladder cancer. HPV vaccine administration in both sexes could be key to prevent the infection caused by high-risk genotypes. Full article

(This article belongs to the Special Issue Diagnosis of Lower Genital Tract Disease)

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