Cervical screening

Molecular testing identifies an infection called human papillomavirus, or HPV. Human papillomavirus (HPV) infection is a cause of nearly all cases of cervical cancer.[6] Most women will successfully clear HPV infections within 18 months. Those that have a prolonged infection with a high-risk type (e.g. types 16, 18, 31, 45) are more likely to develop Cervical Intraepithelial Neoplasia, due to the effects that HPV has on DNA.[7]

The screening process utilizes nucleic acid amplification testing to look for DNA or RNA of the virus present within cervical cells. Some tests can identify up to 14 different types of high risk strains.[2]

Accuracy of HPV testing report:

• sensitivity 88% to 91% (for detecting CIN 3 or higher)[8] to 97% (for detecting CIN2+)[9]
• specificity 73% to 79% (for detecting CIN 3 or higher)[8] to 93% (for detecting CIN2+)[9]

Normal cervical cells in a Pap smear

In the conventional Pap smear, the collected cells are smeared on a microscope slide, and a fixative is applied. The slide is evaluated in a pathology lab to identify cellular abnormalities.

Accuracy of conventional cytology report:[10]

• sensitivity: 55% to 88%
• specificity: 71% to 94%

In liquid based monolayer cytology, the collected cells are placed into a liquid medium. The sample is evaluated in a pathology lab to evaluate cellular abnormalities.

Accuracy of liquid based monolayer cytology report:[10]

• sensitivity 57% to 90%
• specificity 64% to 97%

Visual inspection involves the application of ascetic acid or lugol's iodine solution to the cervix. These solutions highlight abnormal areas for easier identification with the naked eye. A magnifying camera called a colposcope can also be utilized for clearer viewing when available.[2]

Combination testing or co-testing, is when individuals receive both molecular high risk HPV testing and cytology.[11] These results can be utilized to calculate the patient's immediate risk for cervical intraepithelial neoplasia grade 3 or cancer (CIN3+).[12]

The calculated risk can be used to recommend appropriate follow-up options.

In 2021 the World Health Organization published the second edition of WHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention. Within this publication they outline 23 recommendations addressing differences in guidelines for women living with or without HIV. The quality of evidence is rated strong, moderate, low or very low. Some of the recommendations are included below, this is not a comprehensive list.[2]

• HPV molecular testing recommended as primary screening, with or without triage, in all women. HPV screening should occur every 5 to 10 years.
• When used, VIA or cytologic screening should occur every 3 years.
• Begin screening at the age of 30
• Stop screening at the age of 50, as long as most recent two tests were negative

Most countries suggest or offer screening between the ages of 25 and 64.[13] According to the 2015 European guidelines for cervical cancer screening, routine HPV primary screening should not begin under 30 years of age. Primary testing for oncogenic HPV can be used in a population-based programme for cervical cancer screening.[14] In England, the NHS cervical screening programme is available to women aged 25 to 64; women aged 25 to 49 receive an invitation every 3 years and women aged 50 to 64 receive an invitation every 5 years to undergo HPV testing.[15][16] If there is a positive HPV test result, then patients undergo further cytology (Pap smear).[15]

Screening is recommended for women between ages 21 and 65, regardless of age at sexual initiation or other high-risk behaviors.[17][18][19] For healthy women aged 21–29 who have never had an abnormal Pap smear, cervical cancer screening with cervical cytology (Pap smear) should occur every 3 years, regardless of HPV vaccination status.[11] The preferred screening for women aged 30–65 is "co-testing", which includes a combination of cervical cytology screening and HPV testing, every 5 years.[11] However, it is acceptable to screen this age group with a Pap smear alone every 3 years or with an FDA-approved primary high risk HPV test every 5 years.[11] In women over the age of 65, screening for cervical cancer may be discontinued in the absence of abnormal screening results within the prior 10 years and no history of high-grade lesions.[11] Management of screening results is based on recommendations by the American College of Obstetricians and Gynecologists and other professional organizations.[12]

Screening is offered to women aged 18–70, every two years. This is by Pap smear, and regardless of sexual history.[20] In Canada, where screening programmes are arranged at provincial level, the general recommendation is not to begin routine screening until the age of 25 in the absence of specific reasons to, then to screen every three years until the age of 69.[21] In Ontario, "The Ontario Cervical Screening Program recommends that women who are or have been sexually active have a Pap test every 3 years starting at age 21."[22]

The Ministry of Public Health recommends women from age 30-60 receive primary HPV testing every 5 years. Based on the results of the test, those with higher risk strains of HPV will be referred for colposcopy, while those with lower risk strains will be referred for cytology.[23]