figo cervical cancer staging 2020 pdf
[2][4] Cervical cancer typically develops from precancerous changes over 10 to 20 years. 38, No. Discuss the use of diffusion-weighted and dynamic contrast-enhanced MR imaging for endometrial cancer staging. [70], The treatment of cervical cancer varies worldwide, largely due to access to surgeons skilled in radical pelvic surgery, and the emergence of fertility-sparing therapy in developed nations. To compare FIGO 2009 and FIGO 2018 cervical cancer staging criteria with a focus on stage migration and treatment outcomes. [37], Smoking has also been linked to the development of cervical cancer. [19] About 80% of cervical cancers occur in developing countries. oa Update on the diagnosis and management of gestational trophoblastic disease. [55][56][57] Pap test screening every three to five years with appropriate follow-up can reduce cervical cancer incidence up to 80%. Several countries have considered (or are considering) programs to fund HPV vaccination. Impeded diffusion can occur in any normal anatomic structure with a high cellular density. About 1,000 women per year die of cervical cancer in the UK. Jan 07, the tnm and worldwide federation of gynecology and obstetrics figo classifications for staging vaginal cancer are supplied beneath see tables 1 and 2. Diffusion-weighted imaging can also provide quantitative information in the form of ADC values. 57, No. 2, The Showa University Journal of Medical Sciences, Vol. It also provides for a means to compare treatment results among different institu-tions. 1 Although cervical cancer rates are decreasing overall among women in the United States, incidence remains elevated among Hispanic/Latino, Black, and Asian women. 289, No. The previous iteration of the FIGO system subdivided stage I tumors into IA, IB, and IC tumors. [75], Microinvasive cancer (stage IA) may be treated by hysterectomy (removal of the whole uterus including part of the vagina). Data collection and publication will inform future revisions. Presented as an education exhibit at the 2010 RSNA Annual Meeting. An estimated 13,170 new cervical cancers and 4,250 cervical cancer deaths will occur in the United States in 2019. With the old staging system, differentiating between stage IA and IB tumors could be challenging in patients with loss of junctional zone definition or in lesions with poor tumor-to-myometrium contrast, both of which are common pitfalls in endometrial cancer staging (Figs 2, 3) (14,16,17). The American Society of Clinical Oncology guideline has recommendations for different levels of resource availability. Diffusion-weighted MR imaging and dynamic contrast medium–enhanced MR imaging are useful adjuncts to standard morphologic imaging and may improve overall staging accuracy. The presence of an intact enhancing cervical mucosa excludes stromal invasion. Reactive lymph nodes may have high signal intensity at diffusion-weighted MR imaging due to their high cellular density, and impeded diffusion has been reported in both benign and metastatic lymph nodes (12,42). (c) Axial oblique dynamic contrast-enhanced MR image obtained 4 minutes after contrast medium injection shows tumor enhancement (*) with invasion of the outer half of the myometrium (arrow). Google Scholar; 2. Among the Bethesda results: Low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL). [46], Interventions such as playing music during the procedure and viewing the procedure on a monitor can reduce the anxiety associated with the examination. Delayed-phase images obtained 3–4 minutes after contrast medium administration are useful in evaluating for cervical stromal invasion (FIGO stage II). 16, No. In summary, HSV was seen as a likely cause because it is known to survive in the female reproductive tract, to be transmitted sexually in a way compatible with known risk factors, such as promiscuity and low socioeconomic status. Stage IA endometrial cancer in a 61-year-old woman. Stage IIIC2 endometrial cancer in a 74-year-old woman. In this article, we discuss the MR imaging assessment of endometrial cancer in terms of imaging protocol, recent modifications to the FIGO staging system, imaging appearances, and the complementary roles of diffusion-weighted and dynamic contrast-enhanced MR imaging. However, the depth of invasion is difficult to determine due to poor tumor-to-myometrium contrast (arrow). Multiscale fluorescence imaging was enabled by developing and integrating an in vivo fiber-optic microscope. 10, 3 July 2018 | Cancer Imaging, Vol. More recently, CIN2 and CIN3 have been combined into CIN2/3. [45] Medical devices used for biopsy of the cervix include punch forceps. The system offers 3D color reflectance imaging, 3D fluorescence imaging, and augmented reality in real time. Diagnosis is made by history, examination and biopsy. 24, No. (a) Axial oblique T2-weighted MR image demonstrates a hypointense tumor (*) that appears to be confined to the endometrium. [107] It is the most frequently detected cancer during pregnancy, with an occurrence of 1.5 to 12 for every 100,000 pregnancies. 16, No. Appendix II: FIGO staging of Cervical Cancer 39 Appendix 3. Dynamic contrast-enhanced MR images are obtained with a three-dimensional gradient-recalled echo T1-weighted LAVA (liver acquisition volume acceleration) sequence (GE Healthcare) after the administration of 0.1 mmol/kg of gadolinium at a rate of 2 mL/sec (5,12,14). Uterine sarcoma vs adenocarcinoma: Can the MRI distinguish between them? [67] The vaccines are between 92% and 100% effective against HPV 16 and 18 up to at least 8 years. [82] Yet, women are recommended to practice vigilant prevention and follow-up care including Pap screenings/colposcopy, with biopsies of the remaining lower uterine segment as needed (every 3–4 months for at least 5 years) to monitor for any recurrence in addition to minimizing any new exposures to HPV through safe sex practices until one is actively trying to conceive. [73] Evidence suggests chemoradiotherapy may increase overall survival and reduce the risk of disease recurrence compared to radiotherapy alone. L = leiomyoma. [2] It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. It is usually a squamous carcinoma. 1951 — First successful in-vitro cell line. The goal of staging in the management of patients with cancer is to adequately assess the extent of tumor spread in order to more appropriately manage the disease and to allow for more concrete discussion regarding prognosis. It most commonly affects the outer vaginal lips. Alternatively, the patient can fast for 4–6 hours before the procedure, although in our experience, almost all patients require an antiperistaltic agent, even if they have been fasting (5). Imaging modalities such as ultrasound, CT scan, and MRI have been used to look for alternating disease, spread of the tumor, and effect on adjacent structures. 41, No. Cervical cancer is the 12th-most common cancer in women in the UK (around 3,100 women were diagnosed with the disease in 2011), and accounts for 1% of cancer deaths (around 920 died in 2012). The disease is staged using the International Federation of Gynecology and Obstetrics (FIGO) system, which was updated in 2018. Revised FIGO staging for carcinoma of the cervix uteri Int J Gynaecol Obstet. The term cervical intraepithelial neoplasia (CIN) was developed to place emphasis on the spectrum of abnormality in these lesions, and to help standardize treatment. However, there is some controversy in the literature regarding the added value of dynamic contrast-enhanced MR imaging for overall FIGO staging: Although the majority of published studies have shown an improvement in staging accuracy with dynamic contrast-enhanced MR imaging, some authors have found no benefit (14,16,17,22,29–31,34,35). [65] Visual inspection with acetic acid and HPV DNA testing have been tried, though with mixed success.[65]. Other commonly reported pitfalls in assessing the depth of myometrial invasion include tumor extension into the cornua, myometrial compression from a polypoid tumor, poor tumor-to-myometrium contrast (Fig 5), and the presence of leiomyomas (Fig 7) or adenomyosis (14,16,20,24). Previously, stage IIIC referred to any lymphadenopathy (pelvic or retroperitoneal); in the new FIGO system, however, stage IIIC is divided into stage IIIC1 (Fig 9), which is characterized by pelvic lymph node involvement, and stage IIIC2 (Fig 10), which is characterized by paraaortic lymph node involvement. Zeppernick F, Meinhold-Heerlein I. Invasion of the cervical stroma is present posteriorly (arrow) and is better appreciated than on the T2-weighted image. [37] Personal invitations encouraging women to get screened are effective at increasing the likelihood they will do so. Adenocarcinomas account for 90% of endometrial neoplasms, whereas uterine sarcomas are relatively rare and account for only 2%–6%; the remaining histologic types include adenocarcinoma with squamous cell differentiation and adenosquamous carcinoma (4,5). The left ovarian fibroma (F) has not enhanced. [106] It is the second-most common cause of female-specific cancer after breast cancer, accounting for around 8% of both total cancer cases and total cancer deaths in women. Less advanced stages of cervical cancer typically have treatment options that allow fertility to be maintained, if the patient desires. 3, Revista da Associação Médica Brasileira, Vol. Ovarian cancer can spread to pelvic and retroperitoneal nodes. ", "WHO rolls out plan to rid world of cervical cancer, saving millions of lives", "Information about cervical screening for Aboriginal women", "Aboriginal cervical cancer rates parallel health inequity", "Janette Howard speaks on her battle with cervical cancer", "What do women in the U.S. know about human papillomavirus and cervical cancer? [47], Cervical intraepithelial neoplasia, the potential precursor to cervical cancer, is often diagnosed on examination of cervical biopsies by a pathologist. In a study of 71 patients undergoing preoperative CT or MRI, the incidence of nodal metastases at surgery was 28% (20 of 71). vinegar) solution to highlight abnormal cells on the surface of the cervix,[5] with visual contrast provided by staining the normal tissues a mahogany brown with Lugol's iodine. 1,712 Likes, 64 Comments - Mitch Herbert (@mitchmherbert) on Instagram: “Excited to start this journey! Morphologic imaging is of limited value in these cases, and the addition of diffusion-weighted and dynamic contrast-enhanced MR imaging sequences is extremely helpful in assessing the depth of myometrial invasion. Instead, tumors with endocervical glandular invasion are now considered stage I tumors, and tumors with cervical stromal invasion are defined as stage II tumors (Fig 6). *Varies depending on required coverage. Epidemiologists working in the early 20th century noted that cervical cancer behaved like a sexually transmitted disease. [109] Regular twice-yearly Pap tests can reduce the incidence of cervical cancer up to 90% in Australia, and save 1,200 Australian women from dying from the disease each year. There is currently a transition to the 2018 system. Differential enhancement within the endometrial cavity can allow tumor to be distinguished from blood products and debris (16,17,27,28). From the Department of Clinical Radiology, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, England (P.B., A.K.Y., H.C.A., E.S. Guide pratique pour le dépistage des néoplasies cervicales. [citation needed], Cervical cancer is staged by the FIGO system, which is based on clinical examination, rather than surgical findings. For calculation of ADC values, six or more b values should be used to ensure accurate quantification of impeded diffusion (42). This review summarizes the updated staging and treatment of these malignancies. (b) Axial oblique T2-weighted MR image shows the intermediate-signal-intensity tumor (arrow) within the hyperintense endometrial cavity. 4, 1 October 2015 | Acta Radiologica, Vol. The prevalence of endometrial cancer is increasing due to an aging population combined with rising levels of obesity (3). [3] In 2012, an estimated 528,000 cases of cervical cancer occurred, with 266,000 deaths. 59, No. [68] In June 2013, the Japanese Ministry of Health, Labor and Welfare mandated that, before administering the vaccine, medical institutions must inform women that the ministry does not recommend it. All imaging is performed with the patient supine. [132] Janette Howard, the wife of the then-Prime Minister of Australia, John Howard, was diagnosed with cervical cancer in 1996, and first spoke publicly about the disease in 2006. O = right ovary. 40, No. [130], The Australian Cervical Cancer Foundation (ACCF), founded in 2008, promotes 'women's health by eliminating cervical cancer and enabling treatment for women with cervical cancer and related health issues, in Australia and in developing countries. [126] Specific viral subtypes implicated are HPV 16, 18, 31, 45 and others. Can dynamic contrast enhanced magnetic resonance imaging change treatment planning in endometrial carcinoma? Describe the appearance of endometrial cancer at MR imaging. ", "A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions", "Prophylactic human papillomavirus vaccines", "Who invented the VLP cervical cancer vaccines? Staging according to the old systems (ie, FIGO cervical staging systems from 1999, 2009, and 2014) was inaccurate, with 20%–40% of stage IB–IIIB cancers understaged and up to 64% of stage IIIB cancers overstaged (7–9). Alternatives include local surgical procedures such as a loop electrical excision procedure or cone biopsy. [88] However, little evidence was found on its effects on overall survival. Axial, axial oblique, and sagittal fast recovery fast spin-echo T2-weighted images and axial T1-weighted images of the pelvis are obtained (Table 1). Objective Revised staging of patients with locally advanced cervical cancer is based on clinical examination, imaging, and potential surgical findings. Stage III is still composed of three subdivisions: IIIA, IIIB, and IIIC. [103], In Africa outcomes are often worse as diagnosis is frequently at a latter stage of disease. In postmenopausal women, there is thinning of the myometrium secondary to uterine involution, which can make accurate assessment of the depth of myometrial invasion challenging at conventional MR imaging (Fig 5) (22,23). '[131] Ian Frazer, one of the developers of the Gardasil cervical cancer vaccine, is the scientific advisor to ACCF. [97] With treatment, the five-year relative survival rate for the earliest stage of invasive cervical cancer is 92%, and the overall (all stages combined) five-year survival rate is about 72%. Cervical cancer deaths decreased by approximately 74% in the last 50 years, largely due to widespread Pap test screening. 1, Seminars in Nuclear Medicine, Vol. The depth of myometrial invasion is difficult to determine owing to poor tumor-to-myometrium contrast (arrow). [108], Australia had 734 cases of cervical cancer in 2005. 9, 19 October 2015 | Acta Radiologica, Vol. 9,11 Regional nodal metastasis is not included in the FIGO staging criteria. Woran erkennt man Gebärmutterhalskrebs? [23] In advanced disease, metastases may be present in the abdomen, lungs, or elsewhere. [37], Having many pregnancies is associated with an increased risk of cervical cancer. [59], According to the 2010 European guidelines, the age at which to start screening ranges between 20 and 30 years of age, but preferentially not before age 25 or 30 years, and depends on burden of the disease in the population and the available resources. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. [60] In women over the age of 65, screening may be discontinued if no abnormal screening results were seen within the previous 10 years and no history of CIN2 or higher exists. The two leiomyomas (L) demonstrate enhancement. Educational materials also help increase the likelihood women will go for screening, but they are not as effective as invitations. [77][78] A systematic review concluded that more evidence is needed to inform decisions about different surgical techniques for women with cervical cancer at stage IA2. MR appearance of normal uterine endometrium considering menstrual cycle: differentiation with benign and malignant endometrial lesions, Colorectal cancer mimics: a review of the usual suspects with pathology correlation, Endometrial cancer: correlation of apparent diffusion coefficient (ADC) with tumor cellularity and tumor grade, Use of Myometrium as an Internal Reference for Endometrial and Cervical Cancer on Multiphase Contrast-Enhanced MRI. Cancer of the cervix uteri. For accreditation purposes, this protocol should be used for the following procedures AND tumor types: Introduction. [103] The Pap test was integrated into clinical practice in the Nordic countries in the 1960s. Cervical cancer is the third most commonly diagnosed cancer worldwide and the fourth leading cause of cancer death in women . This type of malignancy is not related to high-risk human papillomavirus (HPV). There are conflicting reports in the literature regarding the detection of lymph node metastases at diffusion-weighted MR imaging of gynecologic malignancies. Clear cell carcinoma (CCC) of the uterine cervix is rare, and its etiology is unclear, except for reports of prenatal diethylstilbestrol (DES) exposure. Stage IB endometrial cancer in a 53- year-old woman. [3] In 2018, 570,000 cases of cervical cancer were estimated to have occurred, with over 300,000 deaths. These changes may improve the diagnostic accuracy of MR imaging. Surgical staging of endometrial cancer was first proposed in 1988, and the staging system was updated in 2009 (Table 2) (6). MR Imaging in Corpus Neoplasia: Spectrum of MR Findings, Diagnostic Value of Pelvic MRI for Assessment of the Depth of Myometrial Invasion and Cervical Involvement in Endometrial Cancer: Comparison of New Versus Old FIGO Staging, Endometrial Carcinoma: MR Imaging–based Texture Model for Preoperative Risk Stratification—A Preliminary Analysis, Role of Imaging in Fertility-sparing Treatment of Gynecologic Malignancies, 2018 FIGO Staging Classification for Cervical Cancer: Added Benefits of Imaging, Endometrial Carcinoma: Texture Analysis of Apparent Diffusion Coefficient Maps and Its Correlation with Histopathologic Findings and Prognosis, Endometrial Cancer Staging: A Resident's Primer, MRI of Malignant Neoplasms of the Uterine Corpus and Cervix: Staging, Treatment Planning, and Follow-up. [102] Carcinoma de endometrio monografias. Cancer staging systems are periodically revised to incorporate new information about prognostic factors. (c) On an axial diffusion-weighted MR image (b = 800 sec/mm2), the node (N) demonstrates high signal intensity. For cases treated surgically, information obtained from the pathologist can be used in assigning a separate pathologic stage, but is not to replace the original clinical stage. ); and Department of Radiology, McGill University Health Centre, Montreal, Quebec, Canada (C.R. (b) On a sagittal diffusion-weighted MR image (b = 500 sec/mm2), the tumor (*) is hyperintense with invasion of the upper aspect of the vagina (arrow). 39, No. [64], Pap tests have not been as effective in developing countries. Cervical cancer has many prognostic factors, some of which, such as lymph node metastasis, were not included in the original FIGO staging system. The revised FIGO staging incorporates ovarian, fallopian tube, and peritoneal cancer into the same system. The mortality rate is approximately 50%, worldwide [1]. Two leiomyomas (L) are also present. 27, No. Key changes include simplification of stage I disease and removal of cervical mucosal invasion as a distinct stage. 2015 — HPV Vaccine shown to protect against infection at multiple body sites. Cervical cancer prevention by vaccination and screening, and management by surgery and radiation according to the revised FIGO staging, can reduce cancer incidence and mortality. A left ovarian fibroma (F) is incidentally noted. Key changes incorporated into the 2009 FIGO staging system include simplification of stage I disease and removal of cervical mucosal invasion as a distinct stage. 3, Seminars in Ultrasound, CT and MRI, Vol. [21] Liquid-based cytology may reduced the number of inadequate samples. (b) Sagittal T2-weighted MR image shows the hypointense tumor (*) in the endometrial cavity. The high cost of this vaccine has been a cause for concern. ", "Cervical Cancer: Statistics | Cancer.Net", "Cervical cancer statistics and prognosis", "Screening for cervical cancer: when theory meets reality", "Quality of Life among Female Cancer Survivors in Africa: An Integrative Literature Review", "WHO Disease and injury country estimates", "WHO Fact Sheet on HPV and Cervical Cancer", "Gynecologic Malignancies in Pregnancy: Balancing Fetal Risks With Oncologic Safety", "The projected timeframe until cervical cancer elimination in Australia: a modelling study", "Human papillomavirus vaccine risk and reality", "Association of educational levels with survival in Indian patients with cancer of the uterine cervix", "Multisite HPV16/18 Vaccine Efficacy Against Cervical, Anal, and Oral HPV Infection", "Evidence for single-dose protection by the bivalent HPV vaccine-Review of the Costa Rica HPV vaccine trial and future research studies", "The low incidence of cervical cancer in Jewish women: has the puzzle finally been solved? It relies on nodal size, shape, and internal architecture to help differentiate between benign and metastatic nodes, all of which features have been shown to be highly variable predictors of nodal involvement (25,26). 5, European Journal of Radiology, Vol. 9, No. [86] A wait of at least one year is generally recommended before attempting to become pregnant after surgery. A 52-year-old female presented with heavy irregular menstrual bleeding for several years and new right elbow pain and swelling. 4, © 2021 Radiological Society of North America, Cancer Stat Fact Sheets: sorpus and uterus, Endometrial cancer incidence trends in Europe: underlying determinants and prospects for prevention, CT and MRI of uterine sarcomas and their mimickers, MRI of malignant neoplasms of the uterine corpus and cervix, Revised FIGO staging for carcinoma of the endometrium, Prognostic significance of gross myometrial invasion with endometrial cancer, Prognosis and treatment of endometrial cancer, Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial, Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study, Survival effect of para-aortic lymphadenectomy in endometrial cancer (SEPAL study): a retrospective cohort analysis, The role of dynamic contrast-enhanced and diffusion weighted magnetic resonance imaging in the female pelvis, Myometrial invasion in endometrial cancer: diagnostic performance of diffusion-weighted MR imaging at 1.5-T, Added value of dynamic contrast-enhanced magnetic resonance imaging in predicting advanced stage disease in patients with endometrial carcinoma, History of the FIGO cancer staging system, Myometrial invasion by endometrial carcinoma: assessment with plain and gadolinium-enhanced MR imaging, Normal uterus and FIGO stage I endometrial carcinoma: dynamic gadolinium-enhanced MR imaging, Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study, Benign and malignant diseases of the endometrium, MR imaging evaluation of endometrial carcinoma: results of an NCI cooperative study, Endometrial carcinoma staging by MR imaging, Local-regional staging of endometrial carcinoma: role of MR imaging in surgical planning, Staging of early endometrial carcinoma: assessment with T2-weighted and gadolinium-enhanced T1-weighted MR imaging, Hyperintense uterine leiomyoma at T2-weighted MR imaging: differentiation with dynamic enhanced MR imaging and clinical implications, Lymphatic metastases from pelvic tumors: anatomic classification, characterization, and staging, Comparison of dynamic helical CT and dynamic MR imaging in the evaluation of pelvic lymph nodes in cervical carcinoma, Carcinoma of the uterus: use of gadopentetate dimeglumine in MR imaging, Assessing myometrial invasion by endometrial carcinoma with dynamic MRI, Myometrial invasion of endometrial carcinoma: assessment with dynamic MR and contrast-enhanced T1-weighted images, MR imaging in endometrial carcinoma as a diagnostic tool for the absence of myometrial invasion, Radiologic staging in patients with endometrial cancer: a meta-analysis, Prediction of deep myometrial invasion in patients with endometrial cancer: clinical utility of contrast-enhanced MR imaging—a meta-analysis and Bayesian analysis, Accuracy of MR imaging for the prediction of myometrial invasion of endometrial carcinoma, Evaluation of endometrial carcinoma on magnetic resonance imaging, Diffusion-weighted MRI in the body: applications and challenges in oncology, Diffusion-weighted MR imaging of uterine endometrial cancer, Diagnostic accuracy of the apparent diffusion coefficient in differentiating benign from malignant uterine endometrial cavity lesions: initial results, Myometrial invasion in endometrial cancer: diagnostic accuracy of diffusion-weighted 3.0-T MR imaging—initial experience, Diffusion-weighted single-shot echo-planar imaging with parallel technique in assessment of endometrial cancer, Diffusion-weighted MR imaging of female pelvic tumors: a pictorial review, Detection of lymph node metastasis in cervical and uterine cancers by diffusion-weighted magnetic resonance imaging at 3T, Detection and evaluation of pelvic lymph nodes in patients with gynecologic malignancies using body diffusion-weighted magnetic resonance imaging, Open in Image
[100], Five year survival in the United States for White women is 69% and for Black women is 57%. [27] Also, not only does it aid in the development of HPV, but also if the woman is already HPV-positive, she is at an even greater likelihood of contracting cervical cancer. (b) Axial oblique dynamic contrast-enhanced MR image obtained 4 minutes after contrast medium injection helps confirm deep myometrial invasion (arrow) by the tumor (*). 1, 19 July 2016 | BMC Cancer, Vol. Revised FIGO staging for carcinoma of the cervix uteri. Normal myometrium enhances intensely compared with hypointense endometrial tumor (Figs 1–6). An estimated 13,800 new cases of cervical cancer will be diagnosed in the United States in 2020, and 4,290 people will die of the disease. It has been agreed to implement the 2018 FIGO staging system in the UK from 1 January, 2020. Although intravenous contrast medium was not administered in this case due to renal impairment, diffusion-weighted MR imaging was adequate for disease staging. [122] During the 1960s and 1970s it was suspected that infection with herpes simplex virus was the cause of the disease. The rates of new cases in the United States was 7.3 per 100,000 women, based on rates from 2012 to 2016. [115] With a 42% reduction from 1988 to 1997, the NHS-implemented screening programme has been highly successful, screening the highest-risk age group (25–49 years) every 3 years, and those ages 50–64 every 5 years. Posterior vaginal invasion (arrow) is also noted. The treatment of low-grade lesions may adversely affect subsequent fertility and pregnancy. [3][14] Other risk factors include smoking, a weak immune system, birth control pills, starting sex at a young age, and having many sexual partners, but these are less important.