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Cervical Cancer Screening

Cervical cancer is the 3rd most common gynecologic cancer. More than 90% of cervical cancer cases are associated with high-risk human papillomavirus (hrHPV), which is transmitted by sexual contact. Cervical cancer can be prevented by early detection and treatment of precancerous lesions caused by hrHPV. The methods of detection are cervical cytology and HPV testing. Guidelines vary on when to start screening, with various US societies recommending that screening start between 21 and 25 years of age, while the World Health Organization (WHO) suggests waiting until age 30, especially in resource-limited settings. Guidelines also vary on the preferred method of testing, though HPV testing (with or without cytology) is universally preferred starting at age 30.  Since the screening program was initiated, there has been a 75% decline in the incidence of and mortality from cervical cancer.

Last updated: Jan 12, 2023

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Cervical cancer Cervical cancer Cervical cancer, or invasive cervical carcinoma (ICC), is the 3rd most common cancer in women in the world, with > 50% of the cases being fatal. In the United States, ICC is the 13th most common cancer and the cause of < 3% of all cancer deaths due to the slow progression of precursor lesions and, more importantly, effective cancer screening. Cervical Cancer

  • Cancer of the uterine cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy
  • Major histologic types:
    • Squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC): approximately 80% of cervical cancers
    • Adenocarcinoma: 15%
    • Adenosquamous carcinoma: 3%–5%
  • Associated with human papillomavirus Human papillomavirus Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) ( HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV)):
    • Detected in 99.7% of cervical cancers
    • Subtypes HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) 16 and 18 found in > 70% of cervical cancers

Epidemiology

  • More than 80% of new cases worldwide are from less developed countries.
  • Worldwide:
    • 2020 estimates:
      • > 600,000 diagnosed with cervical cancer Cervical cancer Cervical cancer, or invasive cervical carcinoma (ICC), is the 3rd most common cancer in women in the world, with > 50% of the cases being fatal. In the United States, ICC is the 13th most common cancer and the cause of < 3% of all cancer deaths due to the slow progression of precursor lesions and, more importantly, effective cancer screening. Cervical Cancer
      • > 340,000 died due to cervical cancer Cervical cancer Cervical cancer, or invasive cervical carcinoma (ICC), is the 3rd most common cancer in women in the world, with > 50% of the cases being fatal. In the United States, ICC is the 13th most common cancer and the cause of < 3% of all cancer deaths due to the slow progression of precursor lesions and, more importantly, effective cancer screening. Cervical Cancer
    • Most common cause of cancer in 23 developing countries, primarily in sub-Saharan Africa, South America, and Southeast Asia ASIA Spinal Cord Injuries
  • In the United States:
    • 14,000 new cases of invasive cervical cancer Cervical cancer Cervical cancer, or invasive cervical carcinoma (ICC), is the 3rd most common cancer in women in the world, with > 50% of the cases being fatal. In the United States, ICC is the 13th most common cancer and the cause of < 3% of all cancer deaths due to the slow progression of precursor lesions and, more importantly, effective cancer screening. Cervical Cancer are diagnosed annually.
    • Mean age at diagnosis: 50 years
    • 3rd most common gynecologic cancer diagnosed
    • 18th most common cause of cancer death overal

Risk factors

  • HPV-related:
    • Early onset of sexual activity
    • Multiple sexual partners
    • Multiparity and early age at 1st birth
    • History of vulvar or vaginal squamous intraepithelial neoplasia or cancer
    • Immunosuppression
    • Human immunodeficiency Immunodeficiency Chédiak-Higashi Syndrome virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology ( HIV HIV Anti-HIV Drugs) infection
    • Co-infection with Chlamydia trachomatis Chlamydia trachomatis Type species of Chlamydia causing a variety of ocular and urogenital diseases. Chlamydia or herpes simplex Herpes Simplex A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. Congenital TORCH Infections virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology
  • Non-HPV related:
    • Low socioeconomic status
    • African American race
    • Use of oral contraceptives
    • Cigarette smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases (associated with squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC))
    • Family history Family History Adult Health Maintenance
    • Negative risk factor: circumcised male partners

Screening Rationale

  • Screening Screening Preoperative Care is recommended because:
    • Women 21‒65 years of age are at risk for cervical cancer Cervical cancer Cervical cancer, or invasive cervical carcinoma (ICC), is the 3rd most common cancer in women in the world, with > 50% of the cases being fatal. In the United States, ICC is the 13th most common cancer and the cause of < 3% of all cancer deaths due to the slow progression of precursor lesions and, more importantly, effective cancer screening. Cervical Cancer due to potential exposure to high-risk human papillomavirus Human papillomavirus Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) (hrHPV) through sexual intercourse.
    • A 75% decline in the incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency and mortality Mortality All deaths reported in a given population. Measures of Health Status of cervical cancer Cervical cancer Cervical cancer, or invasive cervical carcinoma (ICC), is the 3rd most common cancer in women in the world, with > 50% of the cases being fatal. In the United States, ICC is the 13th most common cancer and the cause of < 3% of all cancer deaths due to the slow progression of precursor lesions and, more importantly, effective cancer screening. Cervical Cancer occurred in the past 50 years due to screening Screening Preoperative Care.
    • Most cases of cervical cancer Cervical cancer Cervical cancer, or invasive cervical carcinoma (ICC), is the 3rd most common cancer in women in the world, with > 50% of the cases being fatal. In the United States, ICC is the 13th most common cancer and the cause of < 3% of all cancer deaths due to the slow progression of precursor lesions and, more importantly, effective cancer screening. Cervical Cancer are found in women who have not been adequately screened.
    • Cervical cancer Cervical cancer Cervical cancer, or invasive cervical carcinoma (ICC), is the 3rd most common cancer in women in the world, with > 50% of the cases being fatal. In the United States, ICC is the 13th most common cancer and the cause of < 3% of all cancer deaths due to the slow progression of precursor lesions and, more importantly, effective cancer screening. Cervical Cancer usually does not cause symptoms.
  • Screening Screening Preoperative Care is not recommended earlier than age 21 because:
    • Cancerous and precancerous Precancerous Pathological conditions that tend eventually to become malignant. Barrett’s Esophagus lesions are rare before the age of 21.
    • The progression from hrHPV infection → precancerous Precancerous Pathological conditions that tend eventually to become malignant. Barrett’s Esophagus lesions (cervical intraepithelial neoplasia [ CIN CIN An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer]) → invasive cancer takes many years
    • Many precancerous Precancerous Pathological conditions that tend eventually to become malignant. Barrett’s Esophagus lesions and HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease will regress.
    • May lead to more harm from psychological distress and unnecessary procedures

Strategies for Screening

Screening Screening Preoperative Care strategies can be done independently or concurrently (co-testing).

  • Cervical cytology:
    • Ectocervical and endocervical cells are collected to evaluate the transformation Transformation Change brought about to an organism’s genetic composition by unidirectional transfer (transfection; transduction, genetic; conjugation, genetic, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell’s genome. Bacteriology zone (area at risk for cervical cancer Cervical cancer Cervical cancer, or invasive cervical carcinoma (ICC), is the 3rd most common cancer in women in the world, with > 50% of the cases being fatal. In the United States, ICC is the 13th most common cancer and the cause of < 3% of all cancer deaths due to the slow progression of precursor lesions and, more importantly, effective cancer screening. Cervical Cancer).
    • The procedure is performed with either:
    • Preparation methods:
      • Conventional Papanicolaou (Pap) smear: Ectocervical spatula is smeared and the brush rolled onto a slide, with fixative applied immediately
      • Liquid-based thin layer cytology: Collection device is placed and swirled in the liquid fixative solution, which is then processed by the laboratory.
  • HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) testing:

Cervical Cancer Screening for Average-Risk Individuals

The following recommendations are for average-risk individuals. This group includes individuals who are fully vaccinated against HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV).

  • United States Preventive Services Task Force (USPSTF) recommendations:
    • No screening Screening Preoperative Care prior to the age of 21, regardless of sexual history 
    • For ages 21‒29: cytology alone every 3 years
    • For ages 30‒65, options are:
      • Cervical cytology alone every 3 years
      • hrHPV every 5 years
      • Cytology with hrHPV co-testing every 5 years 
    • Screening Screening Preoperative Care ends at the age of 65 if the patient has adequate negative screening Screening Preoperative Care.
  • Updated American Cancer Society recommendations (2020):
    • No screening Screening Preoperative Care prior to the age of 25, regardless of sexual history
    • Screen individuals ages 25‒65
    • Preferred test: primary HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) testing (approved testing that is adequate for screening Screening Preoperative Care by itself) every 5 years
    • If primary HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) testing cannot be done:
      • Co-testing with HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) and cervical cytology every 5 years
      • Cervical cytology alone every 3 years 
    • Screening Screening Preoperative Care ends at age 65 for average-risk individuals with adequate negative screening Screening Preoperative Care.
    • Rationale for the above:
      • Low incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of cervical cancer Cervical cancer Cervical cancer, or invasive cervical carcinoma (ICC), is the 3rd most common cancer in women in the world, with > 50% of the cases being fatal. In the United States, ICC is the 13th most common cancer and the cause of < 3% of all cancer deaths due to the slow progression of precursor lesions and, more importantly, effective cancer screening. Cervical Cancer in those < 24 years of age
      • HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) testing is more specific.
      • About 70% of adolescents have received at least 1 dose of the HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination.
  • World Health Organization recommendations:
  • Adequate negative prior screening Screening Preoperative Care is defined as 1 of the following:
    • 3 consecutive negative cytology results, with the last result within the past 3 years
    • 2 consecutive negative co-test results within the past 10 years, with the most recent test within the past 5 years
    • 2 consecutive negative primary HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) test results within the past 10 years, with the most recent test within the past 5 years

Cervical Cancer Screening for Special Populations

High-risk individuals

Certain conditions have a high risk for cervical cancer Cervical cancer Cervical cancer, or invasive cervical carcinoma (ICC), is the 3rd most common cancer in women in the world, with > 50% of the cases being fatal. In the United States, ICC is the 13th most common cancer and the cause of < 3% of all cancer deaths due to the slow progression of precursor lesions and, more importantly, effective cancer screening. Cervical Cancer, so screening Screening Preoperative Care must be individualized and more frequent:

  • HIV infection HIV infection Human immunodeficiency virus (HIV), a single-stranded RNA virus belonging to the Retroviridae family, is the etiologic agent of acquired immunodeficiency syndrome (AIDS). The human immunodeficiency virus is a sexually transmitted or blood-borne infection that attacks CD4+ T lymphocyte cells, macrophages, and dendritic cells, leading to eventual immunodeficiency. HIV Infection and AIDS: Screening Screening Preoperative Care may start at the time of HIV HIV Anti-HIV Drugs diagnosis, but no sooner than 21 years of age, regardless of sexual history.
  • Immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis: Screening Screening Preoperative Care may start at 21 years of age, regardless of sexual history.
  • In utero exposure to diethylstilbestrol Diethylstilbestrol A synthetic nonsteroidal estrogen used in the treatment of menopausal and postmenopausal disorders. It was also used formerly as a growth promoter in animals. According to the fourth annual report on carcinogens, diethylstilbestrol has been listed as a known carcinogen. Noncontraceptive Estrogen and Progestins (last used in the 1970s, so most relevant in women born prior to 1980)
  • Previous treatment of a high-grade precancerous Precancerous Pathological conditions that tend eventually to become malignant. Barrett’s Esophagus lesion or cervical cancer Cervical cancer Cervical cancer, or invasive cervical carcinoma (ICC), is the 3rd most common cancer in women in the world, with > 50% of the cases being fatal. In the United States, ICC is the 13th most common cancer and the cause of < 3% of all cancer deaths due to the slow progression of precursor lesions and, more importantly, effective cancer screening. Cervical Cancer

Prior hysterectomy

  • Screening Screening Preoperative Care is still recommended in women:
    • With history of subtotal hysterectomy ( cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy intact; typically called a supracervical hysterectomy)
    • With history of cervical intraepithelial neoplasia ( CIN CIN An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer), even after hysterectomy
  • No screening Screening Preoperative Care is recommended in women who meet both of the following criteria:
    • History of a total hysterectomy (which includes removal of the cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy) for a benign Benign Fibroadenoma disease
    • No history of a high-grade precancerous Precancerous Pathological conditions that tend eventually to become malignant. Barrett’s Esophagus lesion ( CIN CIN An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer grade 2 or 3) or cervical cancer Cervical cancer Cervical cancer, or invasive cervical carcinoma (ICC), is the 3rd most common cancer in women in the world, with > 50% of the cases being fatal. In the United States, ICC is the 13th most common cancer and the cause of < 3% of all cancer deaths due to the slow progression of precursor lesions and, more importantly, effective cancer screening. Cervical Cancer

Individuals > 65 years of age

Pap Test

Results (Bethesda system)

The Bethesda system is a standardized reporting of results, which includes the specimen adequacy, general categorization Categorization Types of Variables of findings, and results.

Types of squamous cell epithelial cell abnormalities:

  • Negative for intraepithelial lesion or malignancy Malignancy Hemothorax
  • Atypical squamous cells (ASC): 
    • Some cells seen are not normal but do not meet the requirements to be precancerous Precancerous Pathological conditions that tend eventually to become malignant. Barrett’s Esophagus
    • May be precancerous Precancerous Pathological conditions that tend eventually to become malignant. Barrett’s Esophagus or associated with infection, irritation, or intercourse
    • Categories:
      • ASC of undetermined significance (ASC-US): abnormal cells, but no squamous intraepithelial lesions (SIL)
      • ASC cannot exclude high-grade SILs (HSIL): equivocal findings, but may be a sign of HSIL
  • Squamous intraepithelial lesion (SIL):
    • Premalignant findings for invasive squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC)
    • Low-grade squamous intraepithelial lesion (LSIL):
      • Low-grade dysplasia corresponding to CIN CIN An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer 1 (cervical intraepithelial neoplasia type 1 Type 1 Spinal Muscular Atrophy
      • Early, mild changes in the size or shape of cells
      • May regress on its own
    • High-grade squamous intraepithelial lesion (HSIL):
      • Moderate or high-grade dysplasia (corresponding to CIN CIN An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer 2, CIN CIN An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer 3, or carcinoma in situ)
      • Increased risk of progression to invasive carcinoma (compared with LSIL changes)
  • Squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC): cancer

Glandular cell abnormalities (categorized as endocervical, endometrial, or not otherwise specified):

  • Atypical endocervical, endometrial, or glandular cells (AGC): endometrial or cervical cell changes abnormal, requiring closer evaluation
  • AGC, favor neoplastic: show features that suggest, but are not sufficient for, a diagnosis of adenocarcinoma
  • Endocervical adenocarcinoma in situ ( AIS AIS Scoliosis): premalignant lesion of invasive adenocarcinoma
  • Adenocarcinoma: cancer

Other possible findings reported on cervical cytology reports:

  • Organisms:
    • Trichomonas Trichomonas A genus of parasitic flagellate eukaryotes distinguished by the presence of four anterior flagella, an undulating membrane, and a trailing flagellum. Nitroimidazoles vaginalis
    • Fungal elements (consistent with Candida Candida Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis)
    • Cellular changes consistent with herpes simplex Herpes Simplex A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. Congenital TORCH Infections virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology or cytomegalovirus Cytomegalovirus CMV is a ubiquitous double-stranded DNA virus belonging to the Herpesviridae family. CMV infections can be transmitted in bodily fluids, such as blood, saliva, urine, semen, and breast milk. The initial infection is usually asymptomatic in the immunocompetent host, or it can present with symptoms of mononucleosis. Cytomegalovirus
    • Bacterial vaginosis Bacterial vaginosis Polymicrobial, nonspecific vaginitis associated with positive cultures of gardnerella vaginalis and other anaerobic organisms and a decrease in lactobacilli. It remains unclear whether the initial pathogenic event is caused by the growth of anaerobes or a primary decrease in lactobacilli. Vulvovaginitis
    • Bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology consistent with Actinomyces Actinomyces Actinomyces is an anaerobic, gram-positive, branching, filamentous rod. Actinomyces israelii is the most common species involved in human disease. The organism is commonly found as part of the normal flora in the oral cavity, gastrointestinal tract, and reproductive tract. Actinomyces/Actinomycosis
  • Other non-neoplastic findings may be included:
    • Reactive cellular changes
    • Glandular cells status post-hysterectomy
    • Atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation
    • Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
Pap smear showing bacterial vaginosis with many clue cells hiv

Pap smear showing bacterial vaginosis with many clue cells
Clue cells are vaginal epithelial cells studded with adherent coccobacilli that are best appreciated at the edge of the cells. The bacteria are stained blue-purple by the Pap stain (arrows).

Image: “Cervical cytological changes in HIV-infected patients” by Mwakigonja AR, Torres LM, Mwakyoma HA, Kaaya EE. License: CC BY 2.0, edited by Lecturio

Management of Abnormal Results

Determining risk of CIN CIN An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer 3+

Management of abnormal screening Screening Preoperative Care results is based on a patient’s risk of CIN CIN An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer 3+ (given as a percentage) both now and in 5 years.

  • Risk of CIN CIN An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer 3+ includes:
    • CIN CIN An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer 3
    • AIS AIS Scoliosis
    • Squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC) of the cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy
  • Management based on CIN CIN An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer 3+ risk was chosen because:
    • Persistent HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) infection is necessary for the development of high-grade precancer (HSIL) and cancer.
    • The goal of screening Screening Preoperative Care programs is to prevent cancer by identifying and treating precancer that is likely to progress.
  • Uses a combination of current screening Screening Preoperative Care results and past history (including unknown history) 
  • People with the same overall levels of risk are treated the same way, regardless of the combination of results that yielded the risk level.
  • The same current test result may lead to different management options depending on how prior history/prior results affect the risk.
  • Options for determining a patient’s risk of CIN CIN An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer 3+:
    • Use the ASCCP’s risk-based management guidelines app (paid) or web application (free, but requires registration).
    • Look up risk level in one of the risk tables from the US National Institutes of Health, publicly available at https://CervixCa.nlm.nih.gov/RiskTables.

Risk estimate and management tables

  • Tables give:
    • The immediate/current risk of having CIN CIN An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer 3+
    • The risk of developing CIN CIN An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer 3+ over the next 5 years
    • Recommended management
  • Tables exist for the following situations:
    • Initial abnormal screening Screening Preoperative Care results (see table below):
    • Surveillance Surveillance Developmental Milestones and Normal Growth following abnormal results that did not require immediate colposcopy (see table below):
    • Current colposcopy/ biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma results
    • Surveillance Surveillance Developmental Milestones and Normal Growth following colposcopy/ biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma results < CIN CIN An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer 2 (no treatment):
    • Follow-up after treatment for CIN CIN An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer 2 or CIN CIN An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer 3:
  • Management:
    • Based on a patient’s risk of CIN CIN An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer 3+ either:
      • Immediately/currently or
      • Developing within the next 5 years
    • Specific management recommendations are defined for different levels of risk.
    • The lower limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation of each “risk level” is known as the clinical action threshold Threshold Minimum voltage necessary to generate an action potential (an all-or-none response) Skeletal Muscle Contraction.
    • Choosing immediate vs. 5-year risk levels:
      • If the immediate risk is ≥ 4% → manage based on the immediate CIN CIN An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer 3+ risk level
      • If the immediate risk is < 4 % → manage based on the 5-year CIN CIN An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer 3+ 
  • Note: Colposcopy is a procedure in which a colposcope Colposcope Instruments inserted into the vagina for examination of the tissues of the vagina and cervix by means of a magnifying lens. Diagnostic Procedures in Gynecology ( magnifying device magnifying device Instruments inserted into the vagina for examination of the tissues of the vagina and cervix by means of a magnifying lens. Diagnostic Procedures in Gynecology) is used to enhance visualization of the cervix Cervix The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. Uterus, Cervix, and Fallopian Tubes: Anatomy, identify macroscopic abnormal areas, and guide biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma.

Special situations

  • Unsatisfactory cytology:
    • No HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) or unknown result (any age) or HPV-negative (age ≥ 25) → repeat age-based screening Screening Preoperative Care in 2‒4 months
    • HPV-positive with unknown genotype Genotype The genetic constitution of the individual, comprising the alleles present at each genetic locus. Basic Terms of Genetics (age ≥ 25) options:
    • HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) 16 or 18 positive (age ≥ 25) → colposcopy
  • For patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship < 25 years old with abnormal screening Screening Preoperative Care results:
    • ASC-US or LSIL → repeat cytology in 1 year (preferred) 
    • ASC-H or HSIL → colposcopy
  • For patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with AGC:
    • Atypical endometrial cells →
      • Endometrial sampling PLUS
      • Endocervical sampling 
      • +/– Colposcopy
    • All other AGC →
      • Colposcopy + endocervical sampling (all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
      • Endometrial sampling only if age ≥ 35 or < 35 with abnormal uterine bleeding Abnormal Uterine Bleeding Abnormal uterine bleeding is the medical term for abnormalities in the frequency, volume, duration, and regularity of the menstrual cycle. Abnormal uterine bleeding is classified using the acronym PALM-COEIN, with PALM representing the structural causes and COEIN indicating the non-structural causes. Abnormal Uterine Bleeding, obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity, or other conditions suggesting chronic anovulation Anovulation Suspension or cessation of ovulation in animals or humans with follicle-containing ovaries (ovarian follicle). Depending on the etiology, ovulation may be induced with appropriate therapy. Polycystic Ovarian Syndrome
  • For pregnant patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship:
    • Use the same clinical action thresholds as those for nonpregnant patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.
    • Colposcopy and ectocervical biopsies can be performed during pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care.
    • Contraindicated in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care:
      • Expedited treatment (i.e., treatment without biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma)
      • Endocervical curettage Endocervical Curettage A scraping, usually of the interior of a cavity or tract, for removal of new growth or other abnormal tissue, or to obtain material for tissue diagnosis. It is performed with a curet (curette), a spoon-shaped instrument designed for that purpose. Diagnostic Procedures in Gynecology (typically done with colposcopy)
      • Endometrial sampling
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with a history of HSIL and/or CIN CIN An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer 2+ never return to baseline risk and should continue surveillance Surveillance Developmental Milestones and Normal Growth screening Screening Preoperative Care at 3-year (instead of 5-year) intervals for 25 years.

References

  1. U.S. Preventive Services Task Force, (2018). Cervical cancer: screening. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/cervical-cancer-screening#fullrecommendationstart
  2. The American Cancer Society. (2020). Guidelines for the prevention and early detection of cervical cancer. https://www.cancer.org/cancer/cervical-cancer/detection-diagnosis-staging/cervical-cancer-screening-guidelines.html
  3. Feldman, S., Goodman, A. (2020). Screening for cervical cancer in resource-rich settings. UpToDate. Retrieved December 14, 2020, from https://www.uptodate.com/contents/screening-for-cervical-cancer-in-resource-rich-settings
  4. Frumovitz, M. (2020). Invasive cervical cancer: epidemiology, risk factors, clinical manifestations, and diagnosis. UpToDate. Retrieved December 17, 2020, from https://www.uptodate.com/contents/invasive-cervical-cancer-epidemiology-risk-factors-clinical-manifestations-and-diagnosis
  5. Feldman, S., Crum, C. P. (2020). Cervical cancer screening tests: techniques for cervical cytology and human papillomavirus testing. UpToDate. Retrieved December 17, 2020, from https://www.uptodate.com/contents/cervical-cancer-screening-tests-techniques-for-cervical-cytology-and-human-papillomavirus-testing
  6. Crum, C.P, Huh, W. K., Einstein, M. H. (2022). Cervical cancer screening: the cytology and human papillomavirus report. UpToDate. Retrieved October 3, 2022, from https://www.uptodate.com/contents/cervical-cancer-screening-the-cytology-and-human-papillomavirus-report 
  7. Iniesta, M. D., Schmeler, K. M., Ramirez, P. T. (2016). Tumors of the uterine cervix. In Kantarjian H.M., Wolff R. A. (Eds.), The MD Anderson Manual of Medical Oncology (3rd ed.). McGraw-Hill.
  8. Karjane, N., Ivey, S. (2018). Pap smear. Medscape. https://emedicine.medscape.com/article/1947979-overview#a9
  9. Papadakis, M. A., McPhee, S. J., Bernstein, J. (Eds.). (2020). Cervical cancer. Quick Medical Diagnosis & Treatment 2020. McGraw-Hill.

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