Journal FeatureSTIs/STDs

HPV Extragenital testing sites

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By: Sierra Adkins, MSN, WHNP-BC, WHNP, and Ginny Moore, DNP, WHNP-BC, FAANP

Current clinical practices and strategies

Takeaways:

  • The human papilloma virus (HPV) is the most common sexually transmitted infection in the world.
  • Current HPV testing is limited to cervical screening.
  • Expansion of HPV screening beyond the cervix is essential in decreasing HPV-related cancers worldwide.

ACCORDING TO THE Centers for Disease Control and Prevention (CDC), genital human papillomavirus (HPV) remains the most common sexually transmitted infection (STI) around the globe. The infection impacts 40% of people within 2 years of their first sexual intercourse and most commonly between the ages of 15 to 24 years.

Modes of HPV transmission include skin-to-skin contact with an infected person, autoinoculation from one body site to another, or, less commonly, from an infected pregnant person during childbirth to the infant. Mucosal HPV types frequently affect the vagina, vulva, cervix, and penis; however, the American Cancer Society suggests that they also can infect other mucosal tissues like the anus, foreskin, urethra, eyelids, and inner linings of the nose, mouth, throat, and lungs.

The CDC reports that HPV infection is typically asymptomatic and commonly spreads between individuals without signs of infection. However, HPV infection can result in genital warts, respiratory papillomatosis, and cancer. According to the CDC, HPV is notable for being the most common STI currently responsible for over 40,000 cancer diagnoses annually. Although cervical cancer is the most well-known HPV-related cancer, the infection also has high association with several other cancers. (See HPV and cancer)

HPV and cancer

Human papilloma virus (HPV)-associated cancer is a specific cellular type of cancer diagnosed in a part of the body where HPV is often found, including the anus, cervix, oropharynx, penis, vagina, and vulva.

The Centers for Disease Control and Prevention (CDC) estimates the number of new HPV-associated cancers each year at 27,081 in women and 22,827 in men. HPV-attributable cancers are estimated by multiplying the number of HPV-associated cancers by the percentage attributable to HPV. The CDC estimated that 39,300 cancers (79%) were attributed to HPV each year from 2018 to 2022. The table below shows the estimated percentage of HPV-attributable cancer cases as of 2023.


CDC’s estimated percentage of HPV-attributable cancer cases per year
Cancer sites where HPV is often foundPercentage of cancer estimated to be caused by HPV
Anus91%
Cervix91%
Oropharynx70%
Penis63%
Vagina75%
Vulva69%

Updating your knowledge of current clinical practice relevant to HPV-associated cancers, screening considerations, and prevention will help prepare you to provide evidence-based care.

Screening considerations

Currently, providers screen subjectively for HPV infections through patient histories and objectively through inspection during physical examinations and with cervical cancer screening tests (cytology, primary HPV tests, or co-testing with cytology and HPV). (See current screening recommendations )

Current screening recommendations

The American College of Obstetricians and Gynecologists (ACOG), the U.S. Preventive Services Task Force (USPSTF), and the American Cancer Society (ACS) offer the following screening recommendations for cervical cancer using primary human papilloma virus (HPV) testing and HPV co-testing.

Age range (years)
ACOG and USPSTF
ACS
<21
Screening not recommended
Screening not recommended
21-29
Cytology testing alone every 3 years
Start screening at age 25: primary HPV testing every 5 years (preferred)

OR

Cytology and HPV co-testing every 5 years (acceptable)

OR

Cytology testing alone every 3 years (acceptable)

30-64
Primary HPV testing every 5 years

OR

Cytology and HPV co-testing
every 5 years

OR

Cytology testing alone every
3 years

Primary HPV testing every 5 years (preferred)

OR

Cytology and HPV co-testing every 5 years (acceptable)

OR

Cytology testing alone every 3 years (acceptable)

>65
Stop screening if adequate prior negative screening results (defined as three consecutive negative cytology results or two consecutive co-testing results within the previous 10 years and most recent testing within the past 5 years).

No further screening necessary unless patient has a history of HSIL, CIN 2, CIN 3, adenocarcinoma in situ, high-grade cytology, or persistent ASCUS-H in which continued surveillance is recommended for at least 25 years after treatment even if beyond the age of 65.

Same as ACOG/USPSTF
Any age
with total
hysterectomy (cervix removed)
No further screening necessary unless patient has a history of HSIL, CIN 2, CIN 3, adenocarcinoma in situ, high-grade cytology, or persistent ASCUS-H in which continued surveillance is recommended for at least 25 years after treatment.
Same as ACOG/USPSTF
ASCUS-H = atypical squamous cells, CIN = cervical dysplasia, HSIL = high-grade squamous intraepithelial lesion

Despite the prevalence of HPV in the United States and its precancerous nature, the cervix and vagina remain the only screening sites approved by the U.S. Food and Drug Administration (FDA).

This limited HPV screening prevents identification of the infection in people who don’t have a cervix and those exposed at other sites. Consequently, thousands of infections outside of the cervix could potentially go undetected and progress to significant mucosal cancers at extragenital sites. This is especially concerning given that the CDC states that sex partners likely share HPV types, including high-risk strains.

To potentially improve treatment outcomes, the CDC recommends routine cervical cancer screening to detect HPV before symptom onset and at early stages. Expanded screening to include the CDC’s defined high-risk sites (anal, oropharyngeal, penile, vaginal, and vulvar) would allow for earlier identification of precancerous cells, ultimately preventing late-stage cancer, reducing healthcare costs, and improving quality of life for those infected.

Although some providers use cervical cancer screening tools for the anus to detect high-grade lesions and high-risk HPV, the CDC reported insufficient evidence to support this collection method, and the FDA hasn’t approved it. Further development of FDA-approved HPV testing modalities outside of cervical spatulas, brooms, and brushes could allow for routine HPV testing on sites like the anus, the base of the tongue, and the tip of the penis.

Several factors not explicitly stated in the literature may explain limitations of HPV screening in noncervical sites. They include the broader range of sexual behaviors that facilitate HPV infection at multiple sites and the comparatively underdeveloped testing methods available for those areas.
Even without approved screening at noncervical sites, nurses and providers can assess for signs and symptoms of HPV-associated cancers to facilitate early diagnosis and improved outcomes. (See Symptoms and risk factors.)

Symptoms and risk factors

The Centers for Disease Control and Prevention reported the following symptoms and risk factors for human papilloma virus (HPV)–associated cancers.

Cancer type
Symptoms
Risk factors
Cervical
No early symptoms
Later symptoms include

  • General pelvic discomfort
  • Pain during vaginal penetration
  • Vaginal bleeding
  • High-risk strains like HPV-16 and HPV-18
  • HIV-positive status
  • No prior HPV immunization
Oropharyngeal
  • Bleeding in mouth or throat
  • Bumps or warts in mouth or throat
  • Difficulty swallowing
  • Earache
  • Pain or discomfort when talking
  • Sore or scratchy throat
  • Unexplained weight loss
  • Voice changes
  • Alcohol consumption
  • No prior HPV immunization
  • Tobacco use
Anal
  • Anal itching
  • Bumps and lumps around anus
  • Loss of bowel control
  • Pain
  • Rectal bleeding
  • Rectal discharge
  • Anal warts
  • History of other HPV-attributed genital cancer
  • HIV-positive status
  • Immunocompromised status
  • No prior HPV immunization
  • Receptive anal sex
  • Tobacco use
Penile
  • Color changes
  • Discharge or bleeding from urethra
  • Lumps, bumps, or growths
  • Rash
  • Thickened skin
  • Immunocompromised status
  • Over the age of 49
  • Tobacco use
  • Uncircumcised penis
Vulvar and vaginal
  • Color or texture changes
  • Painful urination
  • Pelvic pain with or without penetration
  • Unusual vaginal bleeding and spotting
  • Watery vaginal discharge
  • History of melanoma or atypical moles
  • History of vulvar intraepithelial neoplasia, lichen sclerosus, cervical cancer, vaginal adenosis, and uterine prolapse
  • HIV-positive status
  • Immunocompromised status
  • Intrauterine exposure to diethylstilbestrol
  • Over the age of 40
  • Tobacco use

Prevention

The FDA approved the first HPV quadrivalent vaccine in 2006, the bivalent in 2009, and the 9-valent in 2014 with the hope of preventing infection with high-risk HPV strains that could progress to cancer. Before the introduction of the Gardasil HPV vaccine, the CDC estimated that 79 million people became infected with HPV in the United States, with 14 million new infections occurring yearly. Now, just 18 years after development of the vaccine, the CDC estimates that over 42 million people in the United States have HPV, with 13 million new infections per year. The CDC describes the 9-valent vaccine as over 90% effective in preventing HPV-related cell changes that can lead to cancer.

Although condoms can prevent most STIs, they haven’t proven successful in completely blocking HPV transmission, according to the CDC, because infected skin remains exposed. For sexually active patients, asking what kinds of sex practices they engage in can help determine the risk of HPV infection at different body sites. Nurses and providers should include discussion of safer sex practices that apply to all potential infection sites.

Strategies to improve HPV screening and prevention

On a systems level, providers and nurses should advocate for hospitals and other practice settings to include HPV vaccination status in their electronic health records. They also should develop guidelines to offer all unvaccinated individuals between the ages of 9 and 45 years an opportunity to start or complete the vaccine series in accordance with current FDA recommendations. When clinics and hospitals keep the vaccine stocked, they can easily administer it to all eligible patients.

Educational programs, professional organizations, and clinical nurse researchers also have a role to play. Nursing and advanced practice program curricula should include the CDC’s most current, evidence-based information on all HPV-associated cancers, screening, and prevention. Professional organizations can take steps to provide educational updates for members in accordance with CDC and FDA revisions and work collectively to advocate for the expansion of HPV prevention. In addition, clinical nurse researchers should continue to work toward developing HPV testing modalities for sites other than the cervix, similar to anal HPV testing in the 2023 Prevent Anal Cancer Self-Swab Study and oropharyngeal HPV testing in the 2025 Oromouth Study.

On a societal level, we should work to educate the public on HPV and its sequelae by sharing reputable information on social media, creating comprehensive sexual health curricula with local health departments to share in schools, and hosting large vaccine events where individuals can bundle vaccines like COVID, influenza, and HPV in accordance with CDC recommendations.

Essential prevention steps

Although the availability and use of HPV vaccines and cervical cancer screenings have improved, more research will help nurses and providers better understand and screen for HPV infections throughout the body. Expanding testing modalities beyond the cervix, paired with increased HPV vaccination and patient education, has the potential to reduce late-stage disease and improve outcomes. Nurse clinicians, educators, and researchers are uniquely positioned to drive these efforts through innovation, advocacy, and patient-centered prevention. Continued research and development of extragenital HPV testing will prove essential in reducing HPV-related cancer burden and advancing equitable screening across all populations.

Sierra Adkins is a women’s health nurse practitioner at Vanderbilt University Medical Center in Nashville, Tennessee. Ginny Moore is retired from Vanderbilt University Medical Center.

American Nurse Journal. 2026; 21(2). Doi: 10.51256/ANJ022612

References

American Cancer Society. The American Cancer Society guidelines for the prevention and early detection of cervical cancer. July 1, 2025. cancer.org/cancer/types/cervical-cancer/detection-diagnosis-staging/cervical-cancer-screening-guidelines.html

American Cancer Society. HPV testing. May 9, 2025. cancer.org/cancer/risk-prevention/hpv/hpv-and-hpv-testing.html

American College of Obstetricians and Gynecologists. Updated cervical cancer screening guidelines: Practice advisory. April 2021. acog.org/clinical/clinical-guidance/practice-advisory/articles/2021/04/updated-cervical-cancer-screening-guidelines

Centers for Disease Control and Prevention. Cancers linked with HPV each year. June 11, 2025. cdc.gov/cancer/hpv/cases.html

Centers for Disease Control and Prevention. Chapter 11: Human papillomavirus. Epidemiology and prevention of vaccine-preventable diseases. April 23, 2024. cdc.gov/pinkbook/hcp/table-of-contents/chapter-11-human-papillomavirus.html

Centers for Disease Control and Prevention. Sexually transmitted infections treatment guidelines, 2021. July 23, 2021. cdc.gov/std/treatment-guidelines/STI-Guidelines-2021.pdf

Hillier B, Waterboer T, Brooks J, et al. Efficacy of oral rinse and other detection methods in detecting oral human papillomavirus infections: The Oromouth cohort study. J Infect. 2025;90(3):106438. doi:10.1016/j.jinf.2025.106438

National Association of Nurse Practitioners in Women’s Health. Position statement: Cervical cancer screening. May 2021. cdn.ymaws.com/npwh.org/resource/resmgr/positionstatement/2024_updates/NPWH_PositionStatement_Cervi.pdf

Nyitray AG, Nitkowski J, McAuliffe TL, et al. Home‐based self‐sampling vs clinician sampling for anal precancer screening: The Prevent Anal Cancer Self‐Swab Study. Intl J Cancer. 2023;153(4):843-53. doi:10.1002/ijc.34553

U.S. Preventive Services Task Force. Cervical cancer: Screening. August 21, 2018. uspreventiveservicestaskforce.org/uspstf/recommendation/cervical-cancer-screening

Key words: human papilloma virus, HPV, HPV screening, extragenital testing

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