History and exam

Key diagnostic factors

common

presence of risk factors

Key factors include age 45-49 years, HPV infection, multiple sexual partners, early onset of sexual activity (younger than 18 years), and immunosuppression.

abnormal vaginal bleeding

Suggests more advanced disease.

postcoital bleeding

Suggests more advanced disease.

uncommon

pelvic or back pain

Suggests more advanced disease.

dyspareunia

Suggests more advanced disease.

cervical mass

On vaginal examination.

cervical bleeding

On vaginal examination or speculum inspection.

Other diagnostic factors

common

mucoid or purulent vaginal discharge

Suggests more advanced disease.

uncommon

bladder, renal, or bowel obstruction

Suggests more advanced disease.

bone pain

May suggest bony metastases.

Risk factors

strong

human papillomavirus (HPV) infection

HPV-16 and 18 are the most common high-risk types. Other high-risk types include 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82.[25][26]

Host polymorphisms and general health status (poor nutrition, smoking, HIV infection, chronic immunosuppression) interact with this risk factor.[34]

age group

In the US, cervical cancer is most commonly diagnosed in midlife (most frequently in women aged 35-44 years).[4]

Median age at diagnosis is 50 years; approximately 20% of women are diagnosed over the age of 65 years.[4]

HIV infection

Incidence of cervical cancer is high in people with HIV infection.[8][9]

Antiretroviral therapy may lower HPV acquisition and reduce prevalence of high-risk HPV in women with HIV infection.[8][35]

early onset of sexual activity (younger than 18)

Believed to act by increased risk of STI, including HPV infection.[5]

multiple sexual partners

Believed to act by increased risk of STI, including HPV infection.[6]

cigarette smoking

Smoking is thought to be an independent risk factor and is associated with a significantly increased risk of squamous cell carcinoma (relative risk 1.5), but not adenocarcinoma.[7]​​[36][37]

immunosuppression

The risk of cervical cancer is increased in patients who are immunosuppressed (e.g., transplant recipients).[10]

in utero exposure to diethylstilbestrol

Women whose mothers took diethylstilbestrol in pregnancy are at increased risk of high-grade cell changes in the cervix, and clear-cell adenocarcinoma of the cervix or vagina.[38][39][40]​​

Use of diethylstilbestrol during pregnancy stopped in the 1970s, so most women affected are aged >50 years. Clear-cell adenocarcinoma in exposed women may occur at a young age (14-23 years); however, elevated risk persists into middle age.[40][41]​​[42][43]​​​ 

Relative risk of clear-cell adenocarcinoma is significantly increased in diethylstilbestol-exposed women (approximately 40 times higher than for unexposed individuals); however, absolute risk is low (approximately 1 in 1000 exposed women) with an estimated cumulative risk of about 1 in 750 exposed women up to age 50 years.[44]

weak

history of STI

History of any STI is associated with increased risk of cervical cancer. This may be related to increased sexual exposure and risk of HPV infection.

Certain STIs may be directly associated with increased risk of cervical cancer. It has been suggested that co-infection with HPV and certain STIs (e.g., chlamydia or trichomonas) may have a synergistic effect.[45][46][47]​​

oral contraceptive pill use

Associated with increased risk of adenocarcinoma, but also cervical cancer as a whole.[36][48]

high parity

Mechanism unclear, but possibly related to association with increased likelihood of HPV infection from increased sexual exposure.[36][49]

uncircumcised male partner

Risk for HPV infection, and cervical cancer diagnosis, appears to be reduced in women whose male partner is circumcised.[50][51][52]​​​​​

micronutrient malnutrition

Whether there is any benefit from supplementation is unknown.[53][54]

low serum folate

Whether there is any benefit from supplementation is unknown.[53]

low vitamin C and E levels

Whether there is any benefit from supplementation is unknown.[54][55]

Meta-analyses have found that high vitamin C and E intake is associated with reduced risk of cervical neoplasia, but these findings are based on low-quality evidence (mainly case-controlled studies).[56][57]

alcohol use

Believed to act by increased risk of STI exposure.[58]

low socioeconomic status

Multifactorial risk conveyed by this association; may include inadequate screening, early onset sexual activity, increased risk of STI, increased risk of high parity, and increased risk of malnutrition.[11]

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