Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis

INTRODUCTION — 

Cancer of the uterine cervix is the third most common gynecologic cancer diagnosis and cause of death among gynecologic cancers in the United States [1]. Cervical cancer has lower incidence and mortality rates than uterine corpus and ovarian cancer, as well as many other cancer sites. However, in countries that do not have access to cervical cancer screening and prevention programs, cervical cancer remains a significant cause of cancer morbidity and mortality.

Human papillomavirus (HPV) is central to the development of cervical neoplasia and can be detected in 99.7 percent of cervical cancers [2]. The most common histologic types of cervical cancer are squamous cell (70 percent of cervical cancers) and adenocarcinoma (25 percent) [3].

The epidemiology, risk factors, clinical manifestations, and diagnosis of invasive cervical cancer will be reviewed here. Screening and prevention, staging, and the management of cervical cancer and preinvasive disease are discussed separately.

●(See "Screening for cervical cancer in resource-rich settings".)

●(See "Invasive cervical cancer: Staging and evaluation of lymph nodes".)

●(See "Management of early-stage cervical cancer".)

●(See "Management of locally advanced cervical cancer".)

●(See "Cervical intraepithelial neoplasia: Management".)

In this topic, we will use the terms "female" or "patient" to describe genetic females. We recognize that not all people with cervical cancer identify as female, and we encourage the reader to consider the specific counseling needs of transgender and gender nonbinary individuals.

EPIDEMIOLOGY

Incidence and mortality — In 2022, cervical cancer accounted for an estimated 661,021 new cancer cases and 348,189 deaths worldwide [4] and was the fourth most common cancer in females [4]. Eighty-four percent of cervical cancer cases were from resource-limited regions [5]. In females in resource-limited countries, cervical cancer was the second most common type of cancer (15.7 per 100,000 females) and the third most common cause of cancer mortality (8.3 per 100,000). On the continent of Africa and in Central America, cervical cancer is the leading cause of cancer-related mortality among females [4,6]; at least one study suggests that the incidence of cervical cancer has been increasing in some parts of Africa since the early 2000s [7].

In the United States, approximately 13,360 new cases of invasive cervical cancer and 4320 cancer-related deaths occur each year [1]. Cervical cancer is the third most common cancer diagnosis and cause of death among gynecologic cancers in the United States, with lower incidence and mortality rates than uterine corpus or ovarian cancer.

Global incidence and mortality rates depend upon the presence of programs for the prevention, screening, diagnosis, and treatment of cervical precancer and cancer. (See "Screening for cervical cancer in resource-rich settings" and "Screening for cervical cancer in resource-limited settings" and "Human papillomavirus vaccination".)

●Due to these interventions, there has been a large downward trend (approximately 75 percent decrease) in the incidence and mortality of cervical cancer over the past 50 years in resource-rich countries [8-14]. For example, in countries such as Australia that have achieved human papillomavirus (HPV) vaccination rates >70 percent, there has been a large (>40 percent) reduction in high-grade dysplasia [11,15]. Incidence and mortality rates have also declined in younger age groups (eg, ages 20 to 24 years), likely as a result of earlier vaccination in this subgroup [16]. (See "Human papillomavirus vaccination", section on 'Cervical, vaginal, and vulvar disease'.)

However, there are some exceptions [17]. For example, in the United States between 2013 and 2021, the annual incidence of cervical cancer in patients ages 30 to 44 years increased from 12.7 to 14.1 per 100,000, respectively [1]. Similarly, the incidence of cervical cancer increased between 2007 and 2019 among White females in low-income countries (hysterectomy corrected incidence of 11.9 and 13.6 per 100,000, respectively) [18].

The incidence of invasive cervical adenocarcinoma and its variants has also increased over the past few decades, particularly in younger patients [19-21]. This may be due to adenocarcinoma being harder to detect with cytology as the lesions are often higher in the cervical canal. Another possible causative factor is an increased exposure to estrogen as the rates are higher in patients who are nulliparous and patients who are obese. (See 'Other' below.)

●Data suggest that cervical cancer screening in conjunction with HPV vaccination can greatly reduce the incidence of cervical cancer in resource-limited settings. These data are discussed in detail elsewhere. (See "Screening for cervical cancer in resource-limited settings", section on 'Importance of HPV vaccination'.)

Race distribution — Estimates of incidence and mortality for cervical cancer vary depending on race/ethnicity. The United States National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program reported estimates of new cancer cases and deaths (per 100,000 population) as follows [22]:

●American Indian/Alaska Native (10.1 and 2.9)

●Hispanic American (10 and 2.5)

●Non-Hispanic Black American (9 and 3.3)

●Non-Hispanic White American (7.1 and 2)

●Asian American or Pacific Islander (6.3 and 1.6)

A higher magnitude of difference in cervical cancer mortality between Black and White females was found in a United States national survey [23]. The study excluded those who reported a prior hysterectomy (thereby changing the denominator and making the cervical cancer mortality rates higher overall) and found the following mortality rates: Black females (10.1 per 100,000) and White females (4.7 per 100,000). The study raises the question of whether there is a higher than previously calculated risk of cervical cancer mortality when only vulnerable females are included (those with a cervix). A limitation of the study is that no differentiation was made between total and supracervical hysterectomy.

Age distribution — Worldwide in 2012, the cumulative risks of developing cervical cancer and of cervical cancer mortality by age 74 years were as follows: resource-rich countries (0.9 percent incidence/0.3 percent mortality) and resource-limited countries (1.6 percent/0.9 percent) [5].

The lifetime risk of developing cervical cancer for United States females, based on national data from 2017 to 2019, was 0.7 percent [22]. The median age at diagnosis of cervical cancer in the United States from 2015 to 2019 was 50 years. Only 2.5 percent of cases were diagnosed in patients ages 85 years or older. In 2019, the United States hysterectomy- and age-adjusted incidence of cervical cancer in females <24 years was 0.08 per 100,000, rising to 4 per 100,000 in females ages 25 to 29 years, and peaking at 19.2 per 100,000 in females ages 60 to 64 years [24]. Thus, some clinicians continue screening females with a prolonged life expectancy through age 74 [23,25].

RISK FACTORS — 

The two major histologic types of cervical cancer, adenocarcinoma and squamous cell carcinoma, and the preinvasive disease that corresponds with these histologies share many of the same risk factors [26-36].

HPV-related — In almost all cases, cervical cancer is due to persistent human papillomavirus (HPV) infection. Risk factors that are associated with HPV-related cancers include:

●Early onset of sexual activity – Compared with age at first intercourse of 21 years or older, the risk is approximately 1.5-fold for 18 to 20 years and twofold for younger than 18 years [26].

●Multiple sexual partners – Compared with one partner, the risk is approximately twofold with two partners and threefold with six or more partners [26].

●A high-risk sexual partner (eg, a partner with multiple sexual partners, history of prior sexually transmitted disease[s], or known HPV infection).

●History of sexually transmitted infections (eg, Chlamydia trachomatis, genital herpes).

●Early age at first birth (younger than 20 years old) and increasing parity (three or more full-term births); these are likely due to exposure to HPV through sexual intercourse [26]. However, parity may have a weaker association with adenocarcinoma as compared with squamous cell carcinoma [37].

●History of vulvar or vaginal squamous intraepithelial neoplasia or cancer (HPV infection is also the etiology of most cases of these conditions).

●Immunosuppression (eg, HIV infection).

Other

●Low socioeconomic status – In the United States, cervical cancer incidence and mortality are higher in patients who live in communities with higher poverty levels compared with lower poverty levels, likely due to limited access to health care and screening programs [38-40].

●Estrogen

•Exogenous estrogens – A collaborative analysis of data from 24 epidemiologic studies found that, among current users of oral contraceptives, the risk of invasive cervical cancer increased with increasing duration of use (≥5 years of use versus never use: relative risk [RR] 1.9, 95% CI 1.69-2.13). The risk declined after use ceased, and by 10 or more years had returned to that of never users [35]. By contrast, in a subsequent systematic review that included 12 studies of patients with cervical cancer, there was insufficient evidence to determine if oral contraceptive use was associated with an increase in the rate of cervical cancer [41].

While some studies suggest that adenocarcinoma appears to have a stronger association with oral contraceptives than does squamous cell cancer [42], others found a similar risk increase with increasing duration of oral contraceptives for both adeno- and squamous cell carcinomas [43,44]. Similarly, exposure to noncontraceptive hormone therapy (eg, postmenopausal estrogen therapy) appears to be a risk factor for adenocarcinoma [45].

By contrast, both the copper and levonorgestrel intrauterine devices (IUDs) may be associated with lower rates of cervical cancer [46]. This is discussed in detail separately. (See "Intrauterine contraception: Background and device types", section on 'Benefits, risks, and patient satisfaction'.)

•Endogenous estrogens – A pooled analysis of data from eight case-control studies suggests that endogenous estrogen (eg, obesity) has a stronger association with adenocarcinoma than squamous cell carcinoma [37].

●Cigarette smoking – Smoking is associated with an increased risk of squamous cell carcinoma of the cervix but not of adenocarcinoma [26,32]. In one study, smoking increased the risk of squamous cell carcinoma by approximately 50 percent (RR 1.50, 95% CI 1.35-1.66) but did not increase the risk of adenocarcinoma (RR 0.86, 95% CI 0.70-1.05) [32].

●Genetics – While there is no well-established model of a genetic basis for cervical cancer, population studies have shown an increased incidence of cervical cancer within families. In the past, such familial clustering had been attributed to shared environmental exposures. However, subsequent data comparing full and half-siblings have demonstrated that heritable risk factors far outweigh the shared environmental components. As an example, a Swedish study of over 9000 siblings or half-siblings with cervical cancer or precancer attributed 64 percent of cases to genetics and only 36 percent to environmental exposures [47]. Investigations are ongoing to identify genetic alterations that may make patients less likely to clear persistent HPV infections and more susceptible to the development of cervical cancer. Findings to date include an association of cervical cancer with a large variety of polymorphisms in a wide variety of genes, including germline variants [48], and those that regulate immunity and susceptibility [49], cytokine production [50,51], angiogenesis [50], tumor suppressor pathways [52,53], and signal transducers and activators of transcription pathways [54].

●Cervical cancer is less common in patients whose sexual partners are circumcised males [27]. (See "Neonatal circumcision: Risks and benefits", section on 'Cervical cancer in partners'.)

PATHOGENESIS — 

Human papillomavirus (HPV) is central to the development of cervical neoplasia and can be detected in 99.7 percent of cervical cancers [2]. The virology and molecular pathogenesis of HPV-associated malignancies are discussed in detail separately. (See "Virology of human papillomavirus infections and the link to cancer".)

Among the more than 40 genital mucosal HPV types identified, only some are known to be oncogenic (table 1) [55]. Subtypes HPV 16 and 18 are found in over 77 percent of all cervical cancers.

There are four major steps in cervical cancer development [56]:

●Oncogenic HPV infection of the metaplastic epithelium at the cervical transformation zone (the junction between the squamous epithelium of the ectocervix and the glandular epithelium of the endocervical canal).

●Persistence of the HPV infection.

●Progression of a clone of epithelial cells from persistent viral infection to precancer.

●Development of carcinoma and invasion through the basement membrane.

While genital tract HPV infection is extremely common, cervical cancer occurs in only a small proportion of HPV-infected patients. It has been estimated that 75 to 80 percent of sexually active adults will acquire genital tract HPV before the age of 50 [57,58]. Most HPV infections are transient, and the virus alone is not sufficient to cause cervical neoplasia. When HPV infection persists, the time from initial infection to development of high-grade cervical intraepithelial neoplasia and, finally, invasive cancer takes an average of 15 years, although more rapid courses have been reported [59].

Herpes simplex virus-2 infection as a cofactor in cervical cancer pathogenesis has been reported in some, but not all, studies [60-63]. Further investigation of this issue is needed.

The disease burden of genital HPV infection includes conditions other than cervical cancer, including anogenital warts, and cancer of the vulva, vagina, anus, and penis [64,65]. (See "Human papillomavirus infections: Epidemiology and disease associations".)

HISTOPATHOLOGY — 

The most common histologic types of cervical cancer are squamous cell carcinoma and adenocarcinoma; such cancers can be HPV associated or HPV independent [66]. The histopathologic types of cervical cancer are listed in the table (table 2).

The distribution of histologic types in the United States is [67,68]:

●Squamous cell carcinoma – 75 percent.

●Adenocarcinoma (including adenosquamous) – 25 percent; the incidence of invasive cervical adenocarcinoma and its variants has increased over the past few decades, particularly in younger patients [19,20,67,69,70].

Adenosquamous tumors exhibit both glandular and squamous differentiation. They may be associated with a poorer outcome than squamous cell cancers or adenocarcinomas [71-73].

The World Health Organization (WHO) and International Endocervical Adenocarcinoma Criteria and Classification (IECC) system distinguish cervical adenocarcinomas into those that are HPV-associated or HPV-independent (table 2) [74,75].

HPV-associated adenocarcinomas include:

•Usual type – Cervical adenocarcinomas of the usual endocervical type account for at least 80 percent of cervical adenocarcinomas. They are characterized by an irregular haphazard arrangement of glands lined by cells resembling those that line normal endocervical glands.

Morphologic variations have been described and include:  

-Villoglandular

-Mucinous type – Mucinous types include intestinal, signet ring, or not otherwise specified

-Invasive stratified mucin-producing intraepithelial lesion

-Adenosquamous

-Mucoepidermoid

-Adenoid basal cell

HPV-independent adenocarcinomas include:

•Gastric type

•Clear cell type

•Mesonephric type

•Endometrioid type – Endometrioid-type adenocarcinomas with the characteristic histology of tubular glands are infrequently diagnosed, but they have a better prognosis than adenocarcinomas of the usual endocervical type [76]. These tumors display histologic features that are identical to endometrial carcinomas, and the possibility of a primary endometrial adenocarcinoma with endocervical extension or drop metastasis must be excluded before the diagnosis of a primary endocervical endometrioid adenocarcinoma is established. Despite the better prognosis, management for endometrioid histology is generally the same as for other cervical adenocarcinomas.

The precursor lesion of most invasive cervical adenocarcinomas is believed to be adenocarcinoma in situ (AIS) (see "Cervical adenocarcinoma in situ"). By contrast, adenosquamous carcinoma is a tumor composed of admixed malignant glandular and squamous elements. It does not appear to originate from AIS and demonstrates more aggressive features than other cervical adenocarcinomas, such as higher tumor grade and lymphovascular invasion [77].

●Other histologies – Neuroendocrine or small cell carcinomas can originate in the cervix in patients but are infrequent [78]. Rhabdomyosarcoma of the cervix is rare and typically occurs in young patients [79,80]. Primary cervical lymphoma and cervical sarcoma are also rare [81-83]. (See "Rhabdomyosarcoma in childhood and adolescence: Clinical presentation, diagnostic evaluation, and staging" and "Small cell neuroendocrine carcinoma of the cervix", section on 'Introduction'.)

Human papillomavirus (HPV) subtypes associated with squamous cell carcinoma are the same as those associated with adenocarcinoma but occur at different frequencies [84,85]. In a systematic review including almost 112,000 HPV-positive cervical cancers from 121 countries, the distribution of HPV subtypes for the two most common histologic types of cervical cancer was [55]:

●Squamous cell carcinoma – HPV 16 (63.7 percent of cases) and 18 (13.2 percent), with HPV types 31, 33, 45, 52, and 58 comprising an additional 18 percent of all squamous cell cancers.

●Adenocarcinoma – HPV 16 (46.4 percent) and 18 (38.5 percent), with HPV types 31, 33, 45, 52, and 58 comprising an additional 12 percent of all adenocarcinomas.

CLINICAL MANIFESTATIONS — 

Early cervical cancer is frequently asymptomatic, underscoring the importance of screening. In asymptomatic patients, cervical cancer may be discovered as a result of cervical cancer screening or incidentally if a visible lesion is discovered upon pelvic examination. (See "Screening for cervical cancer in resource-rich settings" and 'Physical examination' below.)

For those with symptoms, the most common ones at presentation are [86]:

●Irregular or heavy vaginal bleeding

●Postcoital bleeding

Some patients present with a vaginal discharge that may be watery, mucoid, or purulent and malodorous. This is a nonspecific finding and may be mistaken for vaginitis or cervicitis.

Approximately 42 percent of patients have localized disease at diagnosis, 36 percent have regional disease, and 15 percent have distant metastases [1]. Advanced disease may present with pelvic or lower back pain, which may radiate along the posterior side of the lower extremities. Bowel or urinary symptoms, such as pressure-related complaints, hematuria, hematochezia, or vaginal passage of urine or stool, are uncommon and suggest advanced disease. A discussion regarding how cervical cancer spreads and its staging is found elsewhere. (See "Invasive cervical cancer: Staging and evaluation of lymph nodes".)

DIAGNOSIS — 

The diagnosis of cervical cancer is made based upon histologic evaluation of a cervical biopsy.

Physical examination — A pelvic examination should be performed on any patient with symptoms suggestive of cervical cancer. Visualization of the cervix upon speculum examination may reveal a normal appearance or a visible cervical lesion; large tumors may appear to replace the cervix entirely. Any lesion that is visible should be biopsied regardless of previous benign cervical cytology or negative human papillomavirus (HPV) results [87]. The only visible lesions that do not require biopsy are Nabothian cysts, and only when this diagnosis is confirmed by an experienced examiner. (See "Benign cervical lesions and congenital anomalies of the cervix", section on 'Nabothian cysts'.)

Cervical cancer usually originates at the transformation zone (the junction between the squamous epithelium of the ectocervix and the glandular epithelium of the endocervical canal). The lesion may manifest as a superficial ulceration, exophytic tumor in the exocervix, or infiltration of the endocervix. Endophytic tumors can result in a cervix that appears enlarged, smooth, and indurated, often referred to as a "barrel-shaped cervix." Among cervical adenocarcinomas, approximately one-half are exophytic, others diffusely enlarge or ulcerate the cervix, and approximately 15 percent have no visible lesion because the carcinoma is within the endocervical canal.

A thorough pelvic examination, including rectovaginal examination with assessment of tumor size and vaginal or parametrial involvement, is required for staging cervical cancer. This is discussed in detail separately. (See "Invasive cervical cancer: Staging and evaluation of lymph nodes", section on 'All patients: Physical examination and biopsy'.)

Other suspicious physical examination findings are palpable groin or supraclavicular lymph nodes.

Cervical biopsy and colposcopy — Cervical biopsy may be performed as part of an initial evaluation or along with a full staging procedure, depending on the level of suspicion of malignancy and the patient's access to health care. The approach to cervical biopsy differs depending upon the patient's presentation and findings on pelvic examination:

●In patients with a grossly visible lesion, a suspected diagnosis of cancer must be confirmed by a biopsy of the lesion. We prefer to take the biopsy from the area of the lesion that looks most suspicious with care to avoid grossly necrotic areas, as these are often nondiagnostic. Any cervix that is unusually firm or expanded should be sampled by punch biopsy and endocervical curettage, even if the cervical cytology test does not show evidence of neoplasia. Biopsy in patients with gross lesions may result in significant bleeding and even hemorrhage, and practitioners should be adequately prepared with hemostatic agents such as Monsel solution and the ability to pack the vagina should the bleeding be significant.

The depth of invasion, which correlates with the incidence of metastatic disease, is measured from the luminal surface of the tumor or overlying benign epithelium to the deepest invasive tumor nest [88].

●Patients without a visible lesion (eg, asymptomatic, abnormal cervical cytology) should undergo colposcopy with directed biopsy. Patients in settings in which colposcopy is not available may undergo directed biopsy with the aid of visual inspection methods. (See "Colposcopy" and "Screening for cervical cancer in resource-limited settings", section on 'Alternate: Visual inspection methods'.)

●A diagnostic excisional procedure (eg, cervical conization, loop electrosurgical excision procedure) is necessary if high-grade cervical dysplasia and/or microinvasive cancer is suspected but is not found with directed cervical biopsies. Conization is also required in the setting of microinvasive cancer to determine whether conservative or radical surgery is required for treatment.

A negative margin is required to define the microinvasive lesion, and an endocervical curettage (ECC) is recommended to confirm the absence of additional disease. This is particularly important for cervical adenocarcinoma since, in contrast to cervical squamous cell carcinoma, noncontiguous lesions ("skip lesions") are often found. In general, we do not recommend additional biopsies in the setting of a negative conization margin and negative ECC.

If the excisional margin or ECC is positive for invasive tumor, a second conization is mandatory. If there is no residual disease on the second procedure, then a diagnosis of microinvasive (stage IA1 or IA2) disease can safely be made. If the second conization demonstrates additional invasive disease, then it should be classified as invasive disease and staged accordingly. (See "Invasive cervical cancer: Staging and evaluation of lymph nodes" and "Management of early-stage cervical cancer", section on 'Type of surgery'.)

●Techniques for colposcopy and cervical biopsy are discussed in detail separately. (See "Colposcopy".)

Other diagnostic modalities — Imaging studies may be used for staging and evaluation of patients with suspected or known cervical cancer. This is discussed separately. (See "Invasive cervical cancer: Staging and evaluation of lymph nodes", section on 'Staging procedure'.)

DIFFERENTIAL DIAGNOSIS — 

The differential diagnosis of cervical cancer includes other conditions that result in irregular or heavy vaginal bleeding, vaginal discharge, or a visible cervical lesion. Postcoital bleeding, which is the most specific presentation of cervical cancer, may also result from cervicitis and other benign conditions. Evaluation of patients with these conditions is discussed in detail separately. (See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Terminology, evaluation, and approach to diagnosis" and "Approach to the patient with postmenopausal uterine bleeding" and "Vaginitis in adults and adolescents: Initial evaluation".)

Benign tumor-like lesions that may mimic cervical cancer include Nabothian cysts, mesonephric cysts, cervical ectropion, ulcers associated with sexually transmitted infections, reactive glandular changes from inflammation, and endometriosis. (See "Benign cervical lesions and congenital anomalies of the cervix".)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cervical cancer screening, prevention, and management" and "Society guideline links: Treatment of cervical cancer".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Cervical cancer (The Basics)")

●Beyond the Basics topics (see "Patient education: Cervical cancer treatment; early-stage cancer (Beyond the Basics)" and "Patient education: Fertility preservation in early-stage cervical cancer (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Epidemiology

•Cancer of the uterine cervix is the third most common cancer diagnosis and cause of death among gynecologic cancers in the United States. In countries that do not have access to cervical cancer screening and prevention programs, cervical cancer remains a leading cause of cancer deaths among all types of cancer in females. (See 'Incidence and mortality' above.)

•The lifetime risk of developing cervical cancer for United States females is 0.7 percent. The median age at diagnosis of cervical cancer in the United States is 50 years old. (See 'Age distribution' above.)

●Pathogenesis – Human papillomavirus (HPV) is central to the development of cervical neoplasia and can be detected in 99.7 percent of cervical cancers. Subtypes HPV 16 and 18 are found in the majority of cervical cancers (table 1). (See 'Pathogenesis' above.)

●Risk factors – Risk factors for cervical cancer are mostly associated with an increased risk of acquiring or having a compromised immune response to HPV infection; these include early onset of sexual activity, multiple sexual partners, a high-risk sexual partner, history of sexually transmitted infections, history of vulvar or vaginal squamous intraepithelial neoplasia or cancer, and immunosuppression. Cigarette smoking appears to be associated with an increased risk of squamous cell cancer but not adenocarcinoma. (See 'Risk factors' above.)

●Histopathology – The most common histologic types of cervical cancer are squamous cell (75 percent of cervical cancers) and adenocarcinoma (25 percent). The histopathologic types of cervical cancer are listed in the table (table 2). (See 'Histopathology' above.)

●Clinical presentation – Early cervical cancer is frequently asymptomatic, emphasizing the importance of screening. The most common symptoms at presentation are abnormal vaginal bleeding (including postcoital bleeding) and vaginal discharge. A lesion may or may not be visible or palpable on physical examination. (See 'Clinical manifestations' above and 'Physical examination' above.)

●Diagnosis – The diagnosis of cervical cancer is established by biopsy. Symptomatic patients without a visible lesion and those who have only abnormal cervical cytology and/or HPV testing should undergo colposcopy with directed biopsy and, if necessary, diagnostic conization. (See 'Diagnosis' above.)

ACKNOWLEDGMENT — 

We are saddened by the death of Michael Frumovitz, MD, MPH, who passed away in July 2024. UpToDate acknowledges Dr. Frumovitz's past work as an author for this topic.