Human Papillomavirus (HPV) Testing - Cervical Cancer Screening

Indications for Testing

Women 21-65 years of age should be routinely screened for cervical cancer. Recommended screening intervals and testing methods are based on age group.    There is no recommendation for routine HPV screening in males.  All oropharyngeal squamous cell cancers should be tested for high-risk oncogenic HPV. 

Laboratory Testing

HPV Testing in Women – Cervical Cancer Screening

Screening with cervical cytology and/or testing for multiple oncogenic HPV types can lead to the detection of high-grade precancerous cervical lesions and cervical cancer.  High-risk HPV genotypes are necessary for the development of cervical cancer. HPV types 16 and 18 are the most carcinogenic genotypes, accounting for 55-60% and 10-15% of all cervical cancers, respectively.  Low-risk HPV types are unrelated to cervical cancer and have no clinical role in cervical cancer screening or the evaluation of women with abnormal cytology.

Conventional or liquid-based cytology, with or without reflex to hrHPV testing, is the recommended screening method in women 21-29 years of age and should be performed every 3 years.  Cotesting is defined as screening by cytology and HPV testing, and is the preferred screening method in women 30 years and older. This method is more sensitive than cytology alone at detecting cervical abnormalities and has the potential to enable both increased disease detection and increased length of screening intervals.  Recent guidance from the Society of Gynecologic Oncology (SGO) and the ASCCP and endorsed by the American College of Obstetricians and Gynecologists (ACOG) suggests that primary HPV testing can be considered as an alternative screening method to cytology for women starting at 25 years of age. 

Screening Guidelines by Population

Women 21-<25 Years of Age

In women 21-<25 years of age, screening by cytology alone every 3 years is recommended.    ^, 

Women 25-<30 Years of Age

Interim guidance from the SGO/ASCCP suggests that primary HPV screening as an alternative to cytology can be considered for women beginning at 25 years of age.  This method of screening should be repeated no more often than every 3 years in the event of a normal result.  The U.S. Preventive Services Task Force (USPSTF) and ACOG endorse the recommendation.  

Women 30-65 Years of Age

Most major U.S. guidelines endorse the strategy of cytology plus testing for hrHPV types (known as cotesting) in women 30-65 years as an alternative to cytology alone.    ^,  The rationale behind cotesting is that women with normal cytologic test results and no evidence of hrHPV constitute a particularly low-risk group in which screening intervals may be safely lengthened to every 5 years.  HPV and cytology cotesting every 5 years is preferred, but cytology without reflex every 3 years is acceptable.

Women >65 Years of Age

Women older than 65 years need not be screened following an adequate and negative screen; if prior screening was inadequate, cotesting (preferred) or cytology (acceptable) should be performed. Adequate screening is considered three consecutive negative cytology results or two consecutive negative cotesting results within the last 10 years; the most recent of either test must be within the past 5 years. Women with a history of cervical intraepithelial neoplasia grade 2 (CIN2) or a more severe diagnosis should continue routine screening for at least 20 years after the CIN2-positive test.  

Women Posthysterectomy

Screening for vaginal cancer should not be performed at any age in women who have undergone hysterectomy with removal of the cervix and have no history of CIN2+. 

Women Post-HPV Vaccination

Screening practices should not change after HPV vaccination; age-based screening recommendations should be followed. 

HPV Testing in Men

High-risk HPVs are known to cause cancers of the penis or anus. These cancers are uncommon, and only a subset are related to HPV. Currently, there is no HPV test recommended for men, and screening for anal cancer is not routinely recommended for men. However, some experts recommend yearly anal cancer screening by cytology ("anal Pap") for men who have sex with men (MSM) and HIV-positive men (anal cancer is more common in these populations). 

Screening tests are not available for penile cancer. 

HPV Testing in Head and Neck Cancer

Within the head and neck squamous cell cancers (HNSCCs), the overall incidence of HPV-positive cancers is increasing in the U.S., while the incidence of HPV-negative cancers (primarily tobacco and alcohol related) is decreasing. Those malignancies that are HPV positive are recognized as a distinct subset based on etiology, molecular-genetic aberrations, and favorable clinical outcomes. HPV-positive tumors are more common in the tongue and tonsils (lingual and palatine malignancies) and tend to occur in younger individuals who do not have typical risk factors for head and neck cancer (tobacco smoking and alcohol consumption).   

National Comprehensive Cancer Network (NCCN) recommends that oropharyngeal SCCs (OSCCs) be tested for high-risk oncogenic HPV.  Oral HPV type 16 infection increases the risk of oropharyngeal cancer (OC), and a strong causal relationship has been established. HPV types 18, 31, and 33 are responsible for the vast majority of the remaining cases.    Tumors should be assessed for HPV status using a p16 immunohistochemistry (IHC) test.