HPV and Cervical Cancer

Cervical cancer is one of the most prevalent cancers in women worldwide and one of the highest causes of women's cancer-related deaths¹ — 604,127 new cases of cervical cancer were diagnosed in 2020.² Furthermore, cervical cancer disproportionately affects women who face significant barriers to screening; 84% of all cases and 88% of deaths caused by cervical cancer occurred in low- and middle-income countries.³ Yet, the elimination of cervical cancer is within reach with proper vaccination, screening, and treatment.

The link between cervical cancer and human papillomavirus (HPV) has become clear over the past few decades. It is well-known that persistent infection with specific types of HPV account for nearly all cases of cervical cancer.⁴ Because cervical cancer rarely causes overt symptoms in its early stages—when treatment is most effective—it is important to screen for high-risk HPV infections that are at the greatest risk of progressing to cervical precancer and cancer. Identifying women at risk, before disease develops, is an important part of cervical cancer prevention. With today's technologies, no woman should die from cervical cancer.

Worldwide, it is predicted that 8 out of 10 women will be exposed to HPV in their lifetime⁵

Over 600,000 new cases of cervical cancer were diagnosed worldwide in 2020²

Cervical cancer was responsible for approximately 340,000 deaths worldwide in 2020²

HPV is a common sexually transmitted infection, and most women will not know that they or their partners have it. HPV is most often spread through sexual intercourse. It can also be transmitted via non penetrative sexual activity through skin-to-skin contact.⁶

HPV is a small, double-stranded DNA virus that affects epithelial cells such as skin and mucous membranes. There are more than 200 HPV genotypes,⁷ about 30 of which are sexually transmitted.⁸ Most HPV strains are harmless; however, a handful of high-risk types cause infections that can develop into cervical cancer.

High-risk HPV causes over 99% of cervical cancers.⁴ There are 14 high-risk HPV types that are found in most cases.⁹ Two HPV types, HPV 16 and HPV 18, are associated with 70% of all cervical cancers.¹⁰ Globally, genotypes HPV 16 and HPV 18 are more oncogenic and likely to progress to high grade cervical disease than all other high-risk HPV genotypes combined.¹¹

The Progression to Cervical Cancer

While most HPV infections resolve on their own, some infections with high-risk HPV types can progress to cervical intraepithelial neoplasia (CIN), and these precursor lesions can be identified as low- or high-grade. It is possible for lesions to resolve and the infection to clear, but generally higher grade cases are less likely to regress.¹² An HPV infection can progress to cervical precancer - or invasive cancer - years or even decades after the initial HPV exposure.¹³

Early treatment at the precancer stage is critical because in this stage, high-grade lesions and cervical cancers confined to the cervix can be completely excised. If cervical cancer is detected and treated before it has spread, the 5-year survival rate is approximately 92%.¹⁴

HPV's Role in the Development of Cervical Cancer

Over the last 80 years, Pap cytology screening has had a tremendous impact on women’s health. For the last 60 years since the ACS promoted the Pap test as part of cervical cancer screening,1 the use of regular Pap cytology screening, together with the diagnosis and treatment of precancerous lesions, has contributed to an 80% reduction in the incidence and mortality of cervical cancer in countries with systematic screening.2 HPV is a very common virus; it is predicted that 80% of women will be exposed at some point in their life.3 Despite this, in 2020 alone, 604,127 new cases were diagnosed and 341,831 women lost their lives to cervical cancer.4 To reduce the incidence and mortality rates, attention must focus in part on the screening, triage and management of women found to be at risk for cervical cancer. Furthermore, the majority of cervical cancer deaths occur in low to middle income countries where the infrastructure needed to support widescale Pap cytology does not exist.5 New screening solutions are necessary to increase women's access and to implement more optimal prevention strategies.

The Limits of Pap Cytology

Although Pap testing has proven to be a useful screening tool in countries with organized or opportunistic screening programs, there are limitations and drawbacks to using Pap cytology alone:

• Limited sensitivity: Pap cytology has limited sensitivity. When used without adjunct testing, disease may be missed.6,7,8,9    
  
  
• Subjective interpretation: Interpretations of samples are based on individual judgments of pathologists or technicians, which can compromise reproducibility. Guidelines are provided, but no definitive objective standard exists.2,10  
  
  
• Interpretation errors: False-negative reports may occur when pathologists or technicians fail to detect abnormal cells. False-positive results may also occur when normal cells are incorrectly categorized as abnormal.2   
  
  
• Sample quality: When samples are prepared as a smear, quality may not be sufficient to enable acceptable analysis.11
  
  

These issues can lead to over- or underestimation of risk. Overestimation of risk may lead to unnecessary tests or treatments. This can be of particular concern to younger women, who have many false-positive tests and for whom treatment for suspicious lesions may have long-term consequences for fertility and pregnancy. Underestimation of risk can result in delays or absence of action that might prevent or compromise treatment.

The Case for HPV Primary Screening

The discovery of HPV as the cause of cervical cancer has revolutionized cervical cancer prevention strategies.6,12  An HPV DNA test is a more sensitive indicator of risk for a woman's future cervical health than a Pap test alone.13  In fact, leading US medical societies (ACOG,14 ASCCP,15 SGO,16 ACS17) now support HPV primary screening as an option for cervical cancer screening for women ages 25 and older.

Evidence supports high-risk HPV (hrHPV) testing for primary screening of cervical cancer:

• In primary screening, hrHPV testing was proven more sensitive than cytology for detecting ≥CIN2 and ≥CIN3.13
• There is an opportunity to identify those at highest risk, since 70% of cervical cancers are caused by HPV genotypes 16 and 18.18

Multiple U.S. and International guidelines recommend HPV primary screening. Learn more>

Sensitivity is vital in Primary HPV Screening

There is risk of missed disease if a clinically relevant hrHPV infection is not detected in the first round of routine screening. Women with undetected hrHPV infections may progress to cancer.

Per U.S. guidelines every 3-5 years, many other countries follow every 5 years interval

HPV Genotyping: Identify Women at Greatest Risk

Since HPV 16 and 18 confer a higher risk of having precancerous lesions and cervical cancer than other genotypes,19 focusing on these genotypes gives physicians useful details upon which to make effective treatment decisions. Distinguishing HPV 16 and 18 from other high-risk HPV types may identify women at the greatest risk of ≥CIN315 and those that would benefit from colposcopy.