What is Cervical Cancer?

Cervical cancer results from uncontrolled, untreated growth of abnormal cells in the cervix. Human papillomavirus (HPV), an STI, can cause abnormal cells on the cervix to develop and grow.

HPV is found on skin in the genital area and also in the tissues of the vagina, cervix, and mouth. It is primarily transmitted through skin-to-skin contact. Vaginal, anal, and oral sex can also spread HPV, as can digital contact. Over 40 types of HPV can infect the cervix but only 14 of them (referred to as the oncogenic or high-risk HPV types) can cause pre-cancer changes to the cells on the cervix. Of these high-risk types, 2 types (HPV 16 and 18) cause more than 70% of cervical cancers, with five additional types of HPV (HPV 31, 33, 45, 52, and 58) causing an additional 20% of cervical cancers. Overall, more than 95% of all cervical cancers are due to HPV, while approximately 5% are attributable to HIV (women living with HIV are more likely to develop cervical cancer). Two other types of HPV (HPV 6 and 11) cause most cases of genital warts.

Most sexually active women are infected with at least one type of HPV during their lives. In most cases the HPV infection clears (goes away) on its own. In some clients, however, HPV persists and causes cervical pre-cancer lesions, which can develop into cancer. Overall, less than 5.5% of clients 30–44 years of age with persistent HPV infection get cervical cancer.

Cancer of the cervix usually takes at least 10 to 20 years to develop. This means there is a long period of opportunity to detect and treat early cervical cell changes before they become cancer. This is the goal of screening and treatment for cervical pre-cancer lesions.

Who Is at Greatest Risk for Cervical Cancer?

Some factors make clients more likely to be infected by HPV. Other factors enhance the persistence of high-risk types of HPV infection and progression to cervical cancer. Every client benefits from screening and treatment of cervical pre-cancer lesions, but the following factors and characteristics increase the risk of being infected with HPV, developing a persistent HPV infection, and developing cervical pre-cancer or cancer:

• Having multiple sexual partners and/or having a partner who has multiple sexual partners
• Having had many sexual partners over the years, and/or having a sexual partner who has had many sexual partners over the years
• Having a weakened immune system (including those living with HIV, who have 6 times the risk of developing cervical cancer compared with those who don’t have HIV)
• Having other STIs, such as genital herpes, chlamydia, or gonorrhea
• Being young at the time of first intercourse/first birth
• Being a tobacco smoker
• Having a partner who is not circumcised.

Screening and Treatment

Screening for cervical pre-cancer lesions is simple, quick, and generally not painful. Cervical screening should start at age 30 years, or at age 25 for those who are living with HIV. The recommended frequency of screening depends on the screening test used and whether a client is living with HIV. Any cervical pre-cancer lesions (cell changes) that are detected must be treated, whether immediately after a positive primary test, or only after a positive second “triage” test. Further details on screening tests, screening frequency, and treatment are provided below.

Screening Tests

There are 3 different screening tests that may be used, depending on the capacity and conditions in a region. If available, the recommended primary screening test is an HPV nucleic acid amplification test (HPV NAAT). The other 2 types of screening tests are cytology and visual inspection with acetic acid (VIA).

1. HPV NAATs are available in 2 types: HPV DNA NAATs or HPV mRNA NAATs.

• HPV DNA NAATs detect the presence of a virus by detecting the viral DNA.
• HPV mRNA NAATs detect the proteins that cause the HPV-mediated pre-cancer changes of the epithelial cells.

For clients living with HIV, only HPV DNA NAATs are recommended. For clients without HIV, both types of HPV NAATs can be used, but an HPV DNA NAAT is recommended as the preferred primary screening test. Only samples for HPV DNA NAATs may be self-collected.

2. Cytology (conventional Papanicolaou [Pap] smear or liquid-based cytology [LBC]) requires collecting a small amount of cells from the cervix. The sample is sent to a laboratory for analysis. Using cytology requires a well-functioning lab that has quality assurance systems in place.

3. VIA involves looking at the cervix with the naked eye 1 minute after applying a weak vinegar (3–5% acetic acid) solution to it. Maintaining a well-functioning VIA screening program requires training and supervision of providers and ongoing quality control.

Screening Approaches

Two screening approaches can be considered:

a.    In a screen-and-treat approach, the decision to proceed with treatment is made without triage testing (no second screening test and no histopathological diagnosis). HPV NAATs are the recommended screening test in this approach, but VIA can also be used in a screen-and-treat approach while transitioning to the use of HPV NAATs.

b.    In a screen, triage, and treat approach, when the primary screening test is positive, the decision to proceed with treatment is based on the result of a second/triage test. HPV NAATs are the recommended primary screening test in this approach, but cytology can also be used in a screen, triage, and treat approach while transitioning to the use of HPV NAATs.

• i. If an HPV NAAT is used as the primary screening test, then triage tests can be HPV 16/18 genotyping, VIA, colposcopy, or cytology followed by colposcopy. After a positive primary screening result with an HPV NAAT but a negative triage test result, clients do not need treatment, but they do need appropriate follow-up evaluation, and this should be at 2 years for the general population of women, and at 1 year for those living with HIV.
• ii. If cytology is used as the primary screening test, then the triage test is colposcopy. Women who have screened positive on a cytology primary screening test and then have normal results on colposcopy should be retested with HPV DNA NAATs at 12 months and, if negative, move to the recommended screening interval (see below).

After a positive primary screening test result and a positive triage test result, clients should receive treatment immediately or be referred for treatment or further evaluation.

Starting Age and Interval of Screening

• For the general population of women, starting at age 30, HPV DNA NAATs are the recommended screening test in a screen-and-treat approach and also the recommended primary screening test in a screen, triage, and treat approach, with a screening interval of 5–10 years. HPV mRNA NAATs may also be used, with a screening interval of 5 years.
• For the population of women living with HIV, starting at age 25, HPV DNA NAATs are the recommended primary screening test and a screen, triage, and treat approach is suggested rather than in a screen-and-treat approach, with a screening interval of 3–5 years.
• Where HPV testing is not yet operational, WHO suggests a regular screening interval of every 3 years when using VIA or cytology as the sole or primary screening test among both the general population of women and those living with HIV.
• While transitioning to a program with a recommended regular screening interval, screening even just twice in a lifetime is beneficial among both the general population of women and women living with HIV.

Treatment Methods

Screening without treatment does not prevent cervical cancer. If a client screens positive, then treatment (immediately or after further evaluation) must be provided to prevent progression of pre-cancer to cancer. The areas of the cervix that have been identified as abnormal can be removed either by ablation or excision. Ablation is the destruction of the abnormal tissue by freezing with a probe (cryotherapy) or using heat (thermal ablation). Excision involves surgically removing the abnormal tissue using large-loop excision of the transformation zone (LLETZ) or cold knife conization (CKC). Only excisional treatment will result in a tissue specimen for histological examination. Ablation is less effective for larger growths, but excision requires more extensive training and use of local anesthesia on the cervix. No hospital stay is needed for either type of treatment. Both treatments are generally well-tolerated and effective, and every effort should be made to provide treatment at the same facility where screening occurs, and at the same visit when screening occurs. Before treatment, women who have not yet been screened with VIA should be visually inspected using acetic acid to determine transformation zone type, rule out suspected cervical cancer, and determine eligibility for ablation. After treatment, women need to be followed up at 1 year.

Vaccine Available for Prevention

In the mid-2000s, the European Union and the United States Food and Drug Administration approved 2 vaccines against cervical cancer, pre-cancer, and genital warts. Both of these vaccines protect against HPV types 16 and 18, which cause over 70% of cervical cancers. Cervarix protects only against those 2 HPV types, while Gardasil also protects against infection by HPV types 6 and 11, which cause 90% of genital warts. Both vaccines are most effective when administered to clients before they become sexually active. In 2018, Gardasil-9 became available; this newer HPV vaccine protects against an additional 5 types of HPV types that cause another 20% of cervical cancers. Recently, Cecolin, an HPV vaccine manufactured in China, has also received WHO Prequalification.