Exploring the secondary prevention of cervical cancer

Cervical cancer and precancerous cells

According to the report, cervical cancer is one of the most preventable types of cancer and can be easily cured when detected and treated early. Although there are many available tools for the early detection and treatment of cervical cancer, it is still one of the leading causes of cancer death in women globally. More specifically, it is the fourth most common cancer among all women and the second most common cancer in women over 45.

Cervical cancer risk and causes can vary from patient to patient; however, the most common cause of cervical cancer is HPV infection.

Of the 200 HPV genotypes, 12 have been classified as carcinogenetic to humans by the International Agency for Research on Cancer, including HPV 16, 18, 33, 31, 35, 39, 45, 51, 52, 56, 58, and 59. HPV 16 and 18 have been linked to 70% of all cervical cancers worldwide.

This association between HPV and cervical cancer has positioned prophylactic HPV vaccination as the primary prevention mechanism against cervical cancer. The HPV vaccine provides 98%-100% prevention against HPV infections, including HPV 16 and 18.

In addition to primary prevention through the HPV vaccine, secondary prevention through the detection of precancerous lesions is also vital. There are several types of cervical cancer screening, including primary and triage screenings. According to Unitaid, the WHO recommends HPV DNA detection as the primary screening technique; however, several other primary screening tools exist.

Unitaid outlined several kinds of primary cervical screening tests, including HPV DNA, HPV mRNA, cytology, visual inspection with acetic acid (VIA), and AI-based tools.

Beyond these screening tests, Unitaid divides cervical cancer screening and treatment-related products by technology type, including molecular tests, sampling, cytologic techniques, visual assessment and precancer treatment.

Molecular tests

Molecular tests for cervical screening include HPV tests -- such as HPV DNA and mRNA screening -- methylation and other protein biomarkers.

As mentioned, HPV infections are one of the greatest contributors to cervical cancer, which makes HPV screening a vital tool for diagnosing cervical cancer. These tests amplify nucleic material to determine the presence of HPV infection.

DNA-based HPV tests are the primary screening test the WHO recommends for the general population. HPV DNA nucleic acid amplification tests (NAATs) are recommended as the primary screening tool starting at age 30 for the general global population; however, in women living with HIV, these screenings can begin at age 25.

HPV DNA NAATs should be done in five- to 10-year screening intervals for most women, with shorter screening intervals, i.e., three to five years, for women living with HIV.

One of the greatest benefits of HPV DNA NAATs over HPV mRNA NAATs is that the samples can be collected by a healthcare provider or self-collected.

Compared to HPV DNA NAATs, HPV mRNA NAATs are the alternative primary screening test for the general population starting at age 30; however, Unitaid does not offer a screening recommendation for HPV mRNA NAATs in women living with HIV due to insufficient evidence. Unlike the variable range for HPV DNA NAATs, HPV mRNA NAATs are recommended every five years for the general population.

Beyond HPV mRNA and DNA NAATs, other molecular tests can be useful, including HPV partial and extended genotyping tests. According to Unitaid, most HPV tests can also be used for partial genotyping, which helps providers identify high-risk HPV strains.

Additionally, protein-based biomarker testing is another molecular testing tool that detects levels of oncoproteins or HPV antibodies to identify cancerous or precancerous lesions.

Sample collection and self-collection

Another category explored by Unitaid is the sample collection and new self-collection mechanisms for HPV and cervical cancer. Unitaid acknowledges the various components associated with sampling, including collection type, regulatory approval, transport type, stability and cost.

Self-sampling is an emerging tool used for HPV and cervical screenings, allowing women to collect their own vaginal samples, eliminating the need for a gynecological visit to conduct the screening. This makes screening more accessible, supporting new outreach models.

Unitaid states, "Self-care interventions have proven to [strengthen] health care services and improve universal health coverage. Thus, there has been a global effort to develop self-sampling solutions that are accurate, less invasive, adaptable to different contexts, and compatible with HPV testing, helping to overcome multiple barriers related to cervical screening. However, the products listed in this horizon scan section are still under evaluation/validation and not yet recommended and/or commercially available."

Cytology-based testing

Cytology-based testing, including pap smears, has been acknowledged as one of the most valuable screening tools. This type of test is more specific than an HPV test, so it might be a preferred option in some cases. However, these tests are more expensive and resource-intensive, making them less accessible to lower-income communities.

In addition to standard cytology, computer-assisted cytology techniques combine technology and microscopy to analyze samples.

Another emerging cytology tool is dual-stain cytology, which measures the presence of two proteins to identify precancerous lesions.

Visual assessment techniques

There are several visual assessment techniques for cervical cancer, including colposcopy, VIA and enhanced visual assessment tools.

Colposcopy is used after a positive HPV test or abnormal cytology to assess which treatment method is appropriate. This technique magnifies and illuminates the vulva, vaginal wall and cervix with an acetic acid wash and a colposcope -- a light-illuminated, stereoscopic binocular microscope.

New technologies in colposcopy, such as digital imaging and enhanced visualization techniques, assist in the more accurate identification of lesions during follow-up examinations.

VIA is a low-cost method in which acetic acid is applied to the cervix, making abnormal cells more visible to the naked eye. This is useful in low-resource or low-income settings.

Enhanced visual assessment tools being explored include digital coloscopy, AI-enhanced visual evaluation and optoelectrical tools.

Treatment of precancerous lesions

Although tools for screening and identifying HPV and precancerous lesions play a critical role in cervical cancer prevention, they are only effective when positive results are followed by appropriate and timely treatment, such as cryotherapy, thermal ablation or large loop excision of the transformation zone.

Overall, the screening and treatment landscape of precancerous lesions for the secondary prevention of cervical cancer is a diverse and developing field that can provide critical healthcare tools and improve healthcare outcomes for several communities.

Veronica Salib has covered news related to the pharmaceutical and life sciences industry since 2022.